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Biomedical subjects

S Miles

Publications and source records attributed to S Miles.

At least 37 records · Page 2Linked to original sources
PubMed1996

Complete DNA sequence of the mitochondrial genome of Cepaea nemoralis (Gastropoda: Pulmonata).

The nucleotide sequence of a mitochondrial genome of the pulmonate gastropod mollusc Cepaea nemoralis has been determined. Contained within the 14,100 basepairs (bp) are the two ribosomal RNA genes and 13 protein coding genes typical of metazoan mitochondrial genomes. The Cepaea mtDNA does contain a gene for ATPase subunit 8, like the clausiliid pulmonate, Albinaria, and the chiton, Katharina, but unlike the bivalve mollusc, Mytilus. The mitochondrial genetic code of Cepaea is proposed to be the same as that of Mytilus, Katharina, and Drosophila. Only 14 putative tRNA genes are presented, although there is sufficient unassigned sequence to encode the remainder of the expected total of 22 tRNA genes. These 14 tRNA genes are a mixture of standard cloverleaf structures and nonstandard structures containing TV replacement loops as seen in nematode and mosquito mitochondrial genomes. If the eight unidentified tRNA genes are indeed present, very little unassigned sequence would remain to serve as a control region. Genes are transcribed from both strands of the molecule. Base composition is the least biased for any reported animal mitochondrial genome and is also very little skewed between strands using measures independent of base composition. The Cepaea mitochondrial gene order is quite unlike that of any other reported metazoan mtDNA, with the exception of the recently reported partial sequences of Albinaria. No gene boundaries are shared among all the reported molluscan taxa, demonstrating a complete lack of conservation of mitochondrial gene order across the phylum Mollusca.

Animals↗
PubMed1995

Occupational asthma caused by automated salmon processing.

Within 3 months of the opening of a salmon-processing plant in the UK, some workers complained of symptoms suggestive of occupational asthma. A survey of all 291 employees identified 24 (8.2%) with occupational asthma. The employees worked near machines which generated respirable aerosols containing salmon-serum proteins. The IgE response to these proteins was associated with occupational asthma (p < 0.001), with increasing severity of symptoms (p < 0.001), and with working distance from the aerosol source (p = 0.037). The main factor which predisposed to IgE-antibody production and asthma was cigarette smoking (p < 0.001), whereas atopy and a previous allergic history did not. The affected employees were reallocated to a low-exposure worksite and factory ventilation was improved. Eleven showed significant clinical and pulmonary function improvement, and continued in employment. Thirteen who still had symptoms were advised to leave, thereafter becoming symptom-free, and regaining normal respiratory function. Early recognition of symptoms and prompt action to reduce aerosol exposure avoided the long-term reduction in pulmonary functions often associated with occupational asthma.

Adult↗
PubMed1995

Transactivation of cellular genes by human retroviruses.

We have focused this chapter on interactions with two of the best characterized transregulatory genes, tax for HTLV-I/II and Tat for HIV-1. Both genes illustrate the complex interplay between retroviral regulatory genes and cellular gene regulation. In both instances a viral gene of relatively straightforward function in the viral context appears to cause extensive dysregulation of cellular genes, either directly or as a consequence of altered cellular differentiation. Understanding this viral/cellular gene cross-talk may elucidate mechanisms leading to malignant transformation autoimmune disease and to neurologic and paraneoplastic complications such as hypercalcemia for HTLV-I/II, as well as the pathogenesis of immune dysfunction and opportunistic malignancy in HIV-I/II-infected individuals. An understanding of functional mechanisms of these transregulatory viral genes will undoubtedly afford better explanations for the myriad manifestations of retroviral infection.

Animals↗
PubMed1995

Optimal cost-effective timing of cranial ultrasound screening in low-birth-weight infants.

Our aim in this study was to determine whether delaying the initial screening cranial ultrasound on infants of low birth weight until the 2nd week of life affects clinical diagnosis and cost of patient care. Data were reviewed on all premature infants of less than 33 weeks gestation or less than 1500 g birth weight admitted to the Neonatal Intensive Care Unit between January 1989 and August 1992. Babies admitted before August 1991 were screened on day 4 or 5 with a second scan frequently performed on day 14; babies admitted after that date were screened once between days 10-14. Populations were compared for (1) proportion of ultrasound findings considered normal on final diagnosis; (2) incidence of major and minor abnormalities; (3) periventricular leukomalacia (PVL); (4) change in diagnosis from 1st to 2nd week; and (5) number of studies performed per patient. The study group was composed of 499 eligible infants. Demographic features of infants screened in the 1st vs. 2nd week of life were similar, with comparable diagnoses of major and minor intracranial hemorrhage and ventricular dilatation; however, more patients screened in the 1st week had questionable PVL diagnosed (p = 0.04). There was a significant decrease in the number of scans per patient in the group screened in the 2nd week (p < 0.004). Routine screening may be delayed until the 2nd week without compromising patient care. Widespread use of a similar screening protocol would result in significantly fewer studies being performed, with an estimated saving, in the USA, of more than $3 million annually.

Cerebral Hemorrhage↗
PubMed1995

The use of hematopoietic growth factors in treating HIV infection.

Human immunodeficiency virus infection causes multilineage hematopoietic defects. Defects in the production and function of CD4+ helper cells have been the focus of the majority of HIV research, but anemia, neutropenia, and thrombocytopenia are significant clinical problems as well. Bone marrow suppression is the dose-limiting toxicity for a number of antiviral and prophylactic medications. Hematopoietic growth factors such as granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor are used to optimize the delivery of antiretroviral and prophylactic therapy. Because of the expense involved, the most appropriate use of these hematopoietic growth factors remains a subject of intense investigation. This review focuses on recent experimental results.

AIDS-Related Opportunistic Infections↗
PubMed1994

Minnesota public opinion on health care resource allocation.

Creating workable policies for allocating or rationing finite health care resources to meet the needs of individuals as well as the broader society vexes policymakers, providers, and consumers. This paper presents results of a March 1994 Lou Harris survey of 1,006 Minnesotans about health care allocation. Minnesotans believe that allocative or rationing decisions are inevitable and can be discussed. Individualized bedside allocative decisions are preferable to categorical or universal exclusions of some health care benefits. People want comprehensive health care and are willing to let sound clinical judgment, perhaps informed by practice guidelines, selectively withhold some services. The integrity of plan-based allocation or rationing may be best secured and safeguarded by standards that ensure that the decisions are based on patients' best interests, involve trusted clinical decision makers, and include lay participation in the decision making.

Adolescent↗
PubMed1993

Characterization of a region of steric interference at the cannabinoid receptor using the active analog approach.

In this paper, it is hypothesized that the distinction between certain active and inactive cannabinoids is that the inactive analogs possess extra volume associated with their carbocyclic rings that may be responsible for an unfavorable interaction at the cannabinoid receptor. Using the active analog approach, a model is developed of a region of steric interference at this receptor using the active cannabinoids (-)-trans-delta 9-tetrahydrocannabinol, (-)-trans-delta 8-tetrahydrocannabinol, (-)-11-hydroxy-beta-hexahydrocannabinol, and a (-)-trans-11-hydroxy-delta 8-tetrahydrocannabinol dimethylheptyl derivative and the inactive cannabinoids (9S,6aR)-trans-delta 10,10a-tetrahydrocannabinol and a (+)-trans-11-hydroxy-delta 8-tetrahydrocannabinol dimethylheptyl derivative. Each of these molecules satisfy the cannabinoid pharmacophoric requirements, i.e., a phenolic oxygen at C1 and a side chain of acceptable length at C3. Accessible conformers of each molecule were identified by using the method of molecular mechanics as encoded in the MMP2(85) program. The MAP facility within the Chem-X molecular modeling program was then used to calculate the region of steric interference (termed the receptor essential volume, REV) from these accessible conformers. The calculations revealed an REV region located near the top of the carbocyclic ring in the bottom face of the molecule. In order to explore the use of this REV to account for the activities of other cannabinoids, the minimally active classical cannabinoid (-)-11-hydroxy-alpha-hexahydrocannabinol, an active benzofuran cannabinoid, and the active nonclassical cannabinoid CP-47,497 were then studied. In each case, the activity or minimal activity of each compound can be explained on the basis of the ability of one or more accessible conformer of each molecule to clear the REV calculated here. The results of this study provide an explanation at the molecular level for observed activity differences between cannabinoids that exhibit shape differences associated with their carbocyclic rings.

Benzofurans↗
PubMed1993

Oncostatin-M stimulates tyrosine protein phosphorylation in parallel with the activation of p42MAPK/ERK-2 in Kaposi's cells. Evidence that this pathway is important in Kaposi cell growth.

Oncostatin-M (OSM) is a potent mitogen for Kaposi's sarcoma (KS) cells. We studied signaling by the OSM receptor in three AIDS-related KS lines and show induction of tyrosine phosphorylation of 145-, 120-, 85-, and 42-kD substrates. The 42-kD substrate was identified as p42MAPK (mitogen-activated protein kinase), also known as ERK-2. This serine/threonine kinase relays mitogenic signals from receptor tyrosine protein kinases (TPKs) or receptor-associated TPKs to transcriptional activators. The OSM dose dependence for MAP kinase activation and induction of KS cell growth were almost identical, suggesting functional linkage. MAP kinase activation was dependent on tyrosine phosphorylation, and both OSM-induced MAP kinase activity and KS cell growth could be suppressed by TPK inhibitors, genistein and geldanomycin. OSM also stimulated tyrosine phosphorylation of similar substrates and MAP kinase activity in human vein endothelial cells. While it has been proposed that the OSM receptor may include the gp130 subunit of the IL-6 receptor and alpha-chain of leukemia inhibitory factor (LIF) receptor, neither LIF nor r.IL-6 induced tyrosine protein phosphorylation or p42MAPK activation in KS cells. However, r.IL-6 did stimulate tyrosine phosphorylation and p42MAPK activity in the human B cell line, AF-10, while OSM and LIF exerted no effects. Our results indicate that, although the OSM and IL-6 receptors share a common signaling pathway, this pathway is selectively activated by OSM in Kaposi's cells.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Weekly doxorubicin in the treatment of patients with AIDS-related Kaposi's sarcoma. AIDS Clinical Trials Group.

Fifty-three patients with AIDS-related Kaposi's sarcoma and no previous treatment with cytotoxic chemotherapy enrolled in a phase II multicenter study to evaluate the safety and efficacy of weekly doxorubicin treatment. Doxorubicin was given intravenously at a dose of 15 mg/m2. Patients were stratified for purposes of analyses by tumor burden and coexistence of HIV-associated signs and symptoms; stratum I included patients with cutaneous disease alone and no symptoms, and stratum II included patients with visceral disease, tumor-associated edema, a previous opportunistic infection, or systemic symptoms. Fifty-one patients were evaluable for toxicity and 50 for tumor response. Five patients had a partial response (10%); 32, a minor response (64%); 12, no change (24%); and one, progression (2%) as the best measurable response. Partial response durations ranged from 4 to 14 weeks. Fifteen patients subsequently showed progression while on treatment. A significantly greater number of patients in stratum I (20.1%) had a partial response compared with those in stratum II (0%, p = 0.009). The major toxicities included nausea (37%), stomatitis (9.8%), mucositis (13.7%), and moderate to severe neutropenia (71%). Neutropenia was dose limiting and resulted in discontinuation of doxorubicin in 18% of the patients. Two patients developed cardiac toxicity. In conclusion, doxorubicin treatment induced relatively few tumor responses and remission durations were short. Treatment was limited by a high rate of toxicity.

AIDS-Related Opportunistic Infections↗