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Biomedical subjects

M E Lewis

Publications and source records attributed to M E Lewis.

At least 55 records · Page 3Linked to original sources
PubMed1995

Inflammatory bone changes in leprous skeletons from the medieval Hospital of St. James and St. Mary Magdalene, Chichester, England.

The extent and location of an inflammatory bone lesion, periostitis, were examined in 50 leprous skeletons from the Chichester cemetery of the Hospital of St. James and St. Mary Magdalene in Sussex, England. Although the presence of periostitis is not pathognomonic of leprosy, it predominantly indicates dermal and neuropathic changes that the patient would have presented in life. The spread of inflammation across the knee joint and the ossification of the interosseous membrane due to inflammation are also suggested.

Bone and Bones↗
PubMed1994

Assessment of proliferative activity in Wilms' tumour.

The proliferative activity in 26 cases of Wilms' tumour was studied by enumeration of silver-staining nucleolar organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA) staining of the blastemal, epithelial and stromal components of the tumours. The PCNA and AgNOR scores derived from the blastemal (PCNA range 18.9-81.4%, AgNOR range 2.11-4.95) and epithelial (PCNA range 24.1-74.2%, AgNOR range 2.47-4.41) components of the tumours were significantly higher than those of the stromal component (PCNA range 3.4-64.7%, AgNOR range 2.20-4.26). Ten of the patients had died with recurrent or metastatic tumour (mean survival 29 months) while the remaining 16 were disease free (mean follow-up 95 months) at the time of the study. The prognostic significance of PCNA and AgNOR for Wilms' tumour was evaluated by dividing the tumours into groups exhibiting low (PCNA < or = 40 or AgNOR < or = 4) or high (PCNA > 40 or AgNOR > 4) proliferative activity. There was a significant difference in the survival of the two groups for tumours treated with preoperative chemotherapy (PCNA, P = 0.049; AgNOR, P = 0.02), while no significant difference was observed from tumours resected prior to the administration of chemotherapy. The results of this study suggest that assessment of proliferation activity in postchemotherapy Wilm's tumours may be a useful indicator of prognosis.

Cell Division↗
PubMed1993

Insulin-like growth factors: putative muscle-derived trophic agents that promote motoneuron survival.

Treatment of chick embryos in ovo with IGF-I during the period of normal, developmentally regulated neuronal death (embryonic days 5-10) resulted in a dose-dependent rescue of a significant number of lumbar motoneurons from degeneration and death. IGF-II and two variants of IGF-I with reduced affinity for IGF binding proteins, des(1-3) IGF-I and long R3 IGF-I, also elicited enhanced survival of motoneurons equal to that seen in IGF-I-treated embryos. IGF-I did not enhance mitogenic activity in motoneuronal populations when applied to embryos during the period of normal neuronal proliferation (E2-5). Treatment of embryos with IGF-I also reduced two types of injury-induced neuronal death. Following either deafferentation or axotomy, treatment of embryos with IGF-I rescued approximately 75% and 50%, respectively, of the motoneurons that die in control embryos as a result of these procedures. Consistent with the survival-promoting activity on motoneurons in ovo, IGF-I, -II, and des(1-3) IGF-I elevated choline acetyltransferase activity in embryonic rat spinal cord cultures, with des(1-3) IGF-I demonstrating 2.5 times greater potency than did IGF-I. A single addition of IGF-I at culture initiation resulted in the maintenance of 80% of the initial ChAT activity for up to 5 days, during which time ChAT activity in untreated control cultures fell to 9%. In summary, these results demonstrate clear motoneuronal trophic activity for the IGFs. These findings, together with previous reports that IGFs are synthesized in muscle and may participate in motoneuron axonal regeneration and sprouting, indicate that these growth factors may have an important role in motoneuron development, maintenance, and recovery from injury.

Animals↗
PubMed1993

Cycled primer extension: a method for DNA amplification and labeling from templates of unknown sequence.

A method has been developed for simultaneous radiolabeling and amplification of DNA hybridization probes. The method is termed cycled primer extension (CPE). CPE is a series of temperature-driven reactions in which template DNA is successively denatured and extended by a thermostable primer-dependent DNA polymerase. The primers consist of semirandom nanomers of the form 5'-NNN NNN (G/C)(G/C)(G/C)-3'. These nanomers have the capacity to anneal to any template DNA and serve as initial anchors for extension at the high temperatures required for Taq DNA polymerase activity. CPE cycles consist of 94 degrees C denaturation, annealing of primers to template upon ramping to 24 degrees C, and gradual extension of the primer along the template as temperature is ramped back to 94 degrees C. Labeling efficiency with [32P]dCTP was examined and optimized as determined by the relation to ratios of radiolabeled to unlabeled dCTP, by number of cycles, and by primer composition and sequence. CPE probes can be generated without regard to size or sequence of template and have a high specific activity (approximately 10(9) dpm/micrograms). With CPE, hybridization signals equivalent to those from random primed probes are routinely obtained with initial template amounts as low as 1 ng.

DNA↗
PubMed1993

Pharmacological induction of nerve growth factor mRNA in adult rat brain.

Three structurally unrelated compounds, all of which induce nerve growth factor (NGF) in cell culture systems, were assessed for their ability to induce NGF mRNA in adult rat brain using a highly sensitive RNAse protection assay. Interleukin-1 beta (0.5-1 pmol) and 1,25-dihydroxyvitamin D3 (25-25,000 pmol) were extremely potent inducers of NGF mRNA, being respectively at least 50,000 and 4000 times more potent than 4-methylcatechol. These compounds elicited an approximate twofold increase in NGF mRNA in both the hippocampus and cortex, without altering beta-actin mRNA levels after a single intracerebroventricular injection. The duration of NGF induction was dependent on the compound administered. For example, the elevation of NGF mRNA elicited by interleukin-1 beta peaked at 8 h and lasted for at least 24 h. In contrast, the induction of NGF after 1,25-dihydroxyvitamin D3 and 4-methylcatechol administration peaked between 4 and 8 h and was not apparent 24 h after injection. These results demonstrate induction of NGF mRNA in vivo by administration of physiological or pharmacological agents and differentiate these agents by potency and duration of action. Further, these findings indicate that pharmacological induction of NGF may be a viable strategy for the treatment of neurodegenerative disorders such as Alzheimer's disease.

Animals↗
PubMed1993

Insulin-like growth factor-I: potential for treatment of motor neuronal disorders.

Motor neuronal disorders, such as the loss of spinal cord motor neurons in amyotrophic lateral sclerosis or the degeneration of spinal cord motor neuron axons in certain peripheral neuropathies, present a unique opportunity for therapeutic intervention with neurotrophic proteins. Normally, such proteins do not cross the blood-brain barrier, but spinal cord motor neuron axons and nerve terminals lie outside the barrier and thus may be targeted by systemic administration of protein growth factors. Insulin-like growth factor-I (IGF-I) receptors are present in the spinal cord, and, like members of the neurotrophin receptor family, IGF-I receptors mediate signal transduction via a tyrosine kinase domain. IGF-I was found to prevent the loss of choline acetyltransferase activity in embryonic spinal cord cultures, as well as to reduce the programmed cell death of motor neurons in vivo during normal development or following axotomy or spinal transection. Consistent with earlier reports that IGF-I enhances motor neuronal sprouting in vivo, subcutaneous administration of IGF-I increases muscle endplate size in rats. Subcutaneous injections of IGF-I also accelerate functional recovery following sciatic nerve crush in mice, as well as attenuate the peripheral motor neuropathy induced by chronic administration of the cancer chemotherapeutic agent vincristine in mice. Doses of IGF-I that accelerate recovery from sciatic nerve crush in mice result in elevated serum levels of IGF-I which are similar to those obtained following subcutaneous injections of formulated recombinant human IGF-I (Myotrophin) in normal human subjects. Based on these findings, together with evidence of safety in animals and man, clinical trials of recombinant human IGF-I have been initiated in patients with amyotrophic lateral sclerosis and are planned to begin soon in patients with chemotherapy-induced peripheral neuropathies.

Amino Acid Sequence↗
PubMed1993

K-252a and staurosporine promote choline acetyltransferase activity in rat spinal cord cultures.

The protein kinase inhibitor K-252a increased choline acetyltransferase (ChAT) activity in rat embryonic spinal cord cultures in a dose-dependent manner (EC50 of approximately 100 nM) with maximal stimulatory activity at 300 nM resulting in as much as a fourfold increase. A single application of K-252a completely prevented the marked decline in ChAT activity occurring over a 5-day period following culture initiation. Of 11 kinase inhibitors, only the structurally related inhibitor staurosporine also increased ChAT activity (EC50 of approximately 0.5 nM). Effective concentrations of K-252a were not cytotoxic or mitogenic and did not alter the total protein content of treated cultures. Insulin-like growth factor I, basic fibroblast growth factor, ciliary neurotrophic factor, and leukemia inhibitory factor yielded dose-dependent increases in ChAT activity in spinal cord cultures. The combination of K-252a with insulin-like growth factor-I or basic fibroblast growth factor increased ChAT activity up to eightfold over that of untreated controls, which was greater than that observed with each compound alone. K-252a combined with ciliary neurotrophic factor or leukemia inhibitory factor demonstrated no additive or synergistic effects on ChAT activity. These results suggest that there are multiple mechanisms for the regulation of ChAT activity in spinal cord cultures. The enhancement of spinal cord ChAT activity by K-252a and staurosporine defines a new neurotrophic activity for these small organic molecules and raises the possibility that they may activate some regulatory elements in common with the ciliary neurotrophic factor and leukemia inhibitory factor family of neurotrophic proteins.

Alkaloids↗
PubMed1993

Aurintricarboxylic acid protects hippocampal neurons from NMDA- and ischemia-induced toxicity in vivo.

The polymeric dye aurintricarboxylic acid (ATA) has been shown to protect various cell types from apoptotic cell death, reportedly through inhibition of a calcium-dependent endonuclease activity. Recent studies have indicated that there may be some commonalities among apoptosis, programmed cell death, and certain other forms of neuronal death. To begin to explore the possibility of common biochemical mechanisms underlying ischemia- or excitotoxin-induced neuronal death and apoptosis in vivo, gerbils or rats subjected to transient global ischemia or NMDA microinjection, respectively, received a simultaneous intracerebral infusion of ATA or vehicle. As a biochemical marker of neuronal death, spectrin proteolysis, which is mediated by activation of calpain I, was measured in hippocampus after 24 h. ATA treatment resulted in a profound reduction of both NMDA- and ischemia-induced spectrin proteolysis, consistent with the possibility of some common mechanism in apoptosis and other forms of neuronal death in vivo.

Animals↗
PubMed1992

The use of a videotaped questionnaire for studying asthma prevalence. A pilot study among New Zealand adolescents.

OBJECTIVE: To examine the feasibility of measuring asthma prevalence by means of an audio-visual presentation of asthma symptoms and signs (video questionnaire) and to compare this technique with a standard written questionnaire for predicting bronchial hyperresponsiveness. DESIGN: A cross-sectional study comparing the ability of a video questionnaire and a written, interviewer administered questionnaire to predict bronchial hyperresponsiveness. Bronchial responsiveness was measured with hand held nebulisers. SETTING: Community survey of a New Zealand rural secondary school. SUBJECTS: A total of 456 adolescent school children aged 12-19 years (mean 15.5 years). OUTCOME MEASURES: Comparison of the sensitivity and specificity of a standard questionnaire versus a video questionnaire for bronchial hyperresponsiveness. RESULTS: The technique was easy to administer in the community setting. Overall sensitivity and specificity for the prediction of bronchial hyperresponsiveness were similar for the video and interviewer administered questionnaires. CONCLUSIONS: This new technique is easily used in the community setting, and gives predictions of bronchial hyperresponsiveness similar to those of a standard interviewer administered questionnaire. Further examination of the technique in comparisons of asthma prevalence among different populations is planned.

Adolescent↗
PubMed1992

Induction of NGF by isoproterenol, 4-methylcatechol and serum occurs by three distinct mechanisms.

Evidence is provided that isoproterenol, 4-methylcatechol and serum induce NGF by three separate mechanisms. Isoproterenol and 4-methylcatechol induced NGF and NGF mRNA in mouse fibroblast L929 cells in either the presence or absence of serum. Propranolol prevented NGF induction by isoproterenol, but not by 4-methylcatechol or serum. All possible combinations of these inducers resulted in additive increases in the levels of NGF and NGF mRNA.

Animals↗
PubMed1992

Wilms' tumour in New Zealand 1960-1986.

Between 1960 and 1986, 177 cases of Wilms' tumour were reported to the New Zealand National Cancer Registry. There was an equal sex distribution and 93.2% of patients were in the paediatric age group with a mean age of 3.4 years. The mean symptom interval was 2.0 months and the majority of patients presented with localised disease, although the incidence of advanced disease was greater than that reported from other series. The 5-year survival rate for all cases was 52.5%. Data were divided into patients presenting before and after the publication of the first National Wilms' Tumour Study (NWTS) in the United States in 1976. In patients presenting after 1976 the diagnosis was based on histology in 100%, compared to 58.6% in patients before 1977. Treatment was considered curative in a greater proportion of the post-1976 group. Treatment modalities reflected the recommendations of the NWTS and the 5-year survival rate of this group was 78.3%, this being similar to that reported from the NWTS. Multivariate analysis showed patient age, symptom interval, tumour stage and treatment (pre- and post-NWTS) to be independent predictors of survival.

Adolescent↗
PubMed1991

Baller-Gerold syndrome associated with congenital hydrocephalus.

We present a new case of the Baller-Gerold syndrome (BGS) in an infant with prenatally apparent severe hydrocephalus, growth retardation, and cardiac and limb abnormalities detected by ultrasound at 26 weeks of gestational age. Subsequent survival to term and neonatal examination confirmed an unsuspected diagnosis of BGS.

Abnormalities, Multiple↗
PubMed1991

Autoradiographic study of irreversible binding of [3H]beta-funaltrexamine to opioid receptors in the rat forebrain: comparison with mu and delta receptor distribution.

beta-Funaltrexamine (beta-FNA) is an irreversible mu antagonist and a reversible kappa agonist in in vivo and in vitro tests. However, whether it produces irreversible delta antagonism is controversial. In binding studies, it is clear that beta-FNA does not bind irreversibly (it does reversibly) to kappa receptors. Yet there is no consensus as to whether beta-FNA binds irreversibly to mu and/or delta receptors. In this study, irreversible binding of [3H]beta-FNA to opioid receptors was examined in rat forebrain sections in the presence of 200 mM NaCl and its distribution compared with those of mu and delta opioid receptors, labeled by [3H][D-Ala2,MePhe4,Gly-ol5]enkephalin ([3H]DAMGO) and [3H][D-Pen2,D-Pen5]enkephalin ([3H]DPDPE), respectively. Irreversible binding of [3H]beta-FNA was determined as the binding that remained following 5 washes at room temp. for 1, 5, 20, 20, and 20 min each. Non-specific binding was defined by including 10 microM naloxone, beta-chlornaltrexamine (beta-CNA), or beta-FNA in the incubation mixture. At 37 degrees C, specific irreversible binding of [3H]beta-FNA to opioid receptors reached a plateau at 10 nM in 60 min, and constituted 50-70% of total irreversible binding. Series of 4 sections of similar anatomical levels were labeled with [3H]DAMGO, [3H]beta-FNA, [3H]beta-FNA + 10 microM naloxone, beta-CNA, or beta-FNA, and [3H]DPDPE, resp., and exposed to [3H]-Ultrofilm. The distribution of [3H]beta-FNA (5 nM) irreversible labeling is very similar to that of [3H]DAMGO, i.e. patches and subcallosal streaks in caudate-putamen, patches in nucleus accumbens, dense labeling in thalamus, and more binding in the rostral than caudal striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Quantitative non-radioactive in situ hybridization of preproenkephalin mRNA with digoxigenin-labeled cRNA probes.

Non-radioactive detection of mRNA with in situ hybridization histochemistry has emerged as an important new technology for the study of gene expression. Quantitative in situ hybridization studies have generally relied upon counting of autoradiographic grains in the emulsion overlying cells containing hybridized, radioactively labeled probe. However, such high resolution studies require tedious grain counting over individual cells, frequently in addition to weeks of exposure to nuclear emulsion. The present report describes a quantitative, non-radioactive approach to the detection of a specific mRNA in the brain with the advantages of comparatively rapid tissue processing and computerized image analysis. The validity of this approach was tested by measuring the haloperidol-induced increase in the level of preproenkephalin mRNA in striatal sections of the rat brain using an RNA probe labeled with digoxigenin-11-UTP. Detection of probe hybridized to tissue sections was carried out enzymatically following complex formation with an antidigoxigenin-alkaline phosphatase conjugate. Using computerized image analysis, it was found that chronic treatment of rats with haloperidol resulted in a 50 +/- 6% increase in striatal neuronal optical density, a value in good agreement with previous studies using low-resolution radioactive methods, showing a 30-80% increase in striatal preproenkephalin mRNA hybridization signal.

Animals↗
PubMed1991

Secondary acute non-lymphocytic leukemia with monosomy 7 arising 9 years after acute lymphoblastic leukemia in childhood.

We report a case of pediatric acute non-lymphocytic leukemia (ANLL) with monosomy 7 occurring in a child successfully treated for acute lymphoblastic leukemia (ALL) nine years earlier. Acquired monosomy 7 is currently recognized as a distinct therapy-related cytogenetic abnormality which nonrandomly occurs as a late complication of cytotoxic therapy used in the treatment of both malignant and nonmalignant disease. Most commonly, this occurs as a disorder of bone marrow morphology and function characterized as a myelodysplastic syndrome (MDS) or ANLL. This case report emphasizes the need for continued evaluation of long-term survivors of childhood cancer to identify and minimize therapy-related side effects without compromising successful management.

Antineoplastic Combined Chemotherapy Protocols↗