Accidental ingestion of methadone by children in Merseyside.
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Accidents↗
Biomedical subjects
J Manning
Publications and source records attributed to J Manning.
Inactivation of nitric oxide synthase after prolonged incubation of mouse macrophages with IFN-gamma and bacterial lipopolysaccharide.
Large amounts of nitric oxide (NO) are produced by the inducible isoform of NO synthase (iNOS) in many cell types once the iNOS gene is transcriptionally activated. In primary mouse peritoneal macrophages elicited by thioglycolate broth, expression of iNOS follows treatment with IFN-gamma and is synergistically increased by the addition of bacterial LPS. Expression of iNOS is suppressible at transcriptional and translational levels by certain cytokines and microbial products. The present study describes a novel form of inactivation of iNOS that is post-translational and nondegradative. Mouse peritoneal macrophages cultured in the presence of IFN-gamma alone or IFN-gamma plus LPS rapidly depleted the medium of L-arginine, a substrate for iNOS, and stopped producing NO. Repletion of L-arginine permitted cells treated with IFN-gamma alone to resume NO production for at least 5 days, leading to the release of more NO than macrophages were previously believed capable of generating. L-Arginine repletion also boosted NO production by macrophages cultured for up to 2 to 3 days in the presence of IFN-gamma plus LPS, but thereafter, iNOS was inactive in these cells whether or not L-arginine was repleted. Activity of iNOS could be restored by adding both L-arginine and fresh IFN-gamma with or without LPS, likely reflecting the synthesis of new enzyme. However, the inactivation of iNOS seen late in culture with a single application of IFN-gamma plus LPS could be attributed neither to loss of iNOS protein nor to its autoinactivation by NO. Thus, LPS, a co-inducer of iNOS, causes macrophages to inactivate iNOS about 3 days after the onset of its induction. The mechanism, which remains to be identified, is novel for iNOS, in that it decreases neither its amount nor its apparent molecular mass.
Amino Acid Oxidoreductases↗
Fatty acid composition of low-density lipoprotein influences its susceptibility to autoxidation.
Low-density lipoprotein (LDL) oxidation was studied using copper or the water-soluble initiator azobis(2-amidinopropane) dihydrochloride (ABAP) to catalyze the reaction. These studies were carried out with purified, native LDLs that had a well-defined composition and which contained different concentrations of polyunsaturated fatty acids (PUFA) and alpha-tocopherol. The LDL was obtained from nonhuman primates fed diets enriched in cholesterol and one of four types of fatty acids: saturated (Sat), monounsaturated (Mono), omega-6 (omega-6FA), or omega-3 (omega-3FA) fatty acids. The PUFA concentration of the LDLs depended upon the diet and had the following order: omega-6FA > Sat approximately Mono approximately omega-3FA. Linoleic acid was the predominant PUFA in all of the LDLs. The rates of oxidation were linearly dependent upon the concentration of PUFA. When ABAP was used to initiate oxidation the lag time was linearly related to the amount of alpha-tocopherol. However, with copper catalysis no linear correlation was evident. If the different enrichments were analyzed independently, it was found that copper-catalyzed oxidation of LDLs enriched with omega-6 and omega-3 fatty acids showed a linear correlation between the lag time and the amount of alpha-tocopherol but that LDLs enriched with Sat or Mono fatty acids did not show a correlation. These results demonstrate that the rate of oxidation is dependent upon PUFA concentration and that the ability of alpha-tocopherol to inhibit oxidation depends upon the lipid environment and the mode of initiation.
Amidines↗
Effects of ankle braces upon agility course performance in high school athletes.
The purpose of this study was to compare the effects of wearing the Aircast(TM) Sports Stirrup, Aircast(TM) Training brace, Swede-O(TM) brace, and DonJoy(TM) Ankle Ligament Protector while running an agility course. Eighty-five high school athletes with no history of ankle injury and no experience in wearing any ankle support served as subjects. Each subject participated in four separate testing sessions. During sessions 1 and 4, subjects ran the agility course under the control (unbraced) conditions. Sessions 2 and 3 consisted of randomly wearing the ankle braces while running the agility course. A questionnaire concerning support, comfort, and restriction was completed by each subject after wearing each of the braces. An analysis of variance (ANOVA) with repeated measures revealed that a significant difference existed between the agility times. Tukey's post hoc test indicated that a significant difference existed between each ankle brace and the control 2 agility times as well as a control 1 and control 2 time difference. The control time difference was attributed to a learning effect. An ANOVA with repeated measures of only the four braces revealed that a significant difference existed between the agility times. Tukey's post hoc test showed the only difference was between the DonJoy Ankle Ligament Protector and the Aircast Training brace. We concluded: 1) there is limited practical performance effect upon agility while wearing an ankle brace; and 2) an athlete's perceived comfort, support, and performance restriction are contributing factors that may directly influence the effectiveness of ankle bracing.
Journal Article↗
Proliferating cell nuclear antigen (PCNA) expression in chronic lymphocytic leukemia (CLL).
Chronic Lymphocytic Leukemia (CLL) is usually an indolent disorder which in some patients assumes an aggressive clinical course. In order to assess at presentation the prognosis of a given patient, several staging systems and prognostic variables have been proposed including the expression of the Proliferating Cell Nuclear Antigen (PCNA). PCNA is a 36 kd nuclear protein, the regulation of which is cell cycle-dependent. In CLL, PCNA levels correlate with cell proliferation, clinical stage and the lymphocyte doubling time (LDT). Furthermore, preliminary data suggests that PCNA expression may also predict response to Fludarabine-based chemotherapy. Since PCNA is a cofactor for Delta DNA polymerase, PCNA overexpression in CLL may also reflect the intrinsic DNA repair activity of the leukemic cells and thus their resistance to chemotherapy. Further studies aiming at modulation of PCNA expression in CLL cells may clarify this issue and may offer a future new therapeutic strategy with which to treat this disorder.
Antigens, Neoplasm↗
Technology assessment applied: a comparison of ophthalmic diagnostic techniques to detect diabetic retinopathy among Aboriginal people in central Australia.
Diabetes mellitus is one of the non-communicable diseases that has accompanied Aboriginal exposure to Western life style. The prevalence of diabetes mellitus is higher in the Aboriginal population than in non-Aboriginal Australians (Holding, 1985) and many Aboriginals who have diabetes mellitus develop diabetic retinopathy. Early detection facilitates treatment and prevention of blindness, a sequela of diabetic retinopathy. This paper describes the use of technology assessment as a framework for comparing two diagnostic technologies, fundal camera and ophthalmoscope, for use with Aboriginal people in central Australia.
Australia↗
Prognostic value of proliferating cell nuclear antigen expression in chronic lymphoid leukemia.
Chronic lymphocytic leukemia (CLL) is a usually indolent disease that can assume an aggressive clinical course in some patients. To develop assays that would be predictive of how a particular patient's disease would evolve, we studied the expression of proliferating cell nuclear antigen (PCNA) by Western blotting in 40 patients with CLL. The concentration of PCNA, a cofactor for delta DNA-dependent DNA polymerase, is indicative of the proliferative state of the cell. Significantly lower PCNA levels were observed in earlier stage CLL when compared with more advanced disease. The leukemic cell proliferative rate, assessed by lymphocyte doubling time and flow cytometry, also correlated significantly with the level of PCNA expression. These results suggest that a high level of PCNA in the cells of CLL patients at presentation identifies a subgroup of patients whose CLL cells have a higher proliferative activity and who may, therefore, have a potentially shorter survival.
Actins↗
Specificity and function of gamma delta T lymphocytes.
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Animals↗
A Comparison of Skin Interface Temperature Response Between the ProHeat Instant Reusable Hot Pack and the Standard Hydrocollator Steam Pack.
The ProHeat(trade mark) reusable hot pack is being used increasingly as a substitute for the standard hydrocollator steam pack. This study evaluated the effects of these two modalities on skin temperature. Seventeen subjects were studied during separate 30-minute applications of a ProHeat pack with a wet barrier, a ProHeat pack with a dry barrier, a hydrocollator pack, and a control pack on their nondominant calf. We measured the skin interface temperature and pack surface temperature during each application with surface thermocouples. The skin interface temperature rise time to the minimum therapeutic temperature (104 degrees F) and the total time at and above the minimum therapeutic temperature, for each application, were analyzed using an analysis of variance (ANOVA) with repeated measures (p<.05). The ProHeat pack application, with one layer of wet toweling as a barrier, was not significantly different from the hydrocollator steam pack application. We conclude that the ProHeat pack, prepared with a wet barrier, can be considered a viable alternative to the standard hydrocollator steam pack.
Journal Article↗
Cytomorphologic, immunocytochemical, and nucleic acid flow cytometric study of 50 lymph nodes by fine-needle aspiration. Comparison with results obtained by subsequent excisional biopsy.
Fifty patients with clinically suspected or previous diagnosis of lymphoma underwent fine-needle aspiration (FNA) and subsequent excisional biopsy of their lymph nodes. Results of cytologic diagnosis made from the direct smears in conjunction with immunocytochemical study of cytospin preparations and nucleic acid flow cytometric study (FCM) were compared with the results obtained from histologic sections, cryostat-immunohistochemical study, and nucleic acid FCM performed on resected lymph nodes. This study demonstrates (1) results of immunocytochemical and DNA-FCM analysis of FNA-derived material are comparable in the majority of cases to those obtained from surgical specimens, (2) immunostaining of cytospin preparations for immunoglobulin (Ig) gives less background staining and in certain cases is easier to interpret than when performed on frozen sections, and (3) monotypia in FNA in conjunction with cytomorphologic study is 100% specific for lymphoma, and polytypic staining for Ig does not exclude HD, T-cell lymphoma, or B-cell malignancy focally involving a lymph node.
Adult↗
Pharmacokinetics, safety, and pharmacologic effects of fosinopril sodium, an angiotensin-converting enzyme inhibitor in healthy subjects.
The pharmacokinetics, pharmacodynamics, and safety of fosinopril sodium (SQ 28,555), a new orally active angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 73 healthy men in two separate studies. In study I, doses ranging from 10 to 640 mg were administered once daily for 3 days to seven groups of five subjects each. Serum aldosterone levels, ACE activity, and sitting blood pressure were determined, as were pharmacokinetic parameters of fosinoprilat, the active diacid of fosinopril. In a dose-tolerance study (study II), 80 and 160 mg of the drug were administered in doses of 40 mg bid and 80 mg bid for 2 weeks. Pharmacokinetics were determined on days 1 and 14, and blood pressure and ACE activity were measured daily. One hour after all doses of fosinopril, serum ACE activity was undetectable. Peak blood levels of fosinoprilat occurred at about 3 hours after dosing, and linear kinetics of the diacid were observed. ACE activity remained undetectable for more than 24 hours after the treatment was stopped in study II. Serum aldosterone levels were decreased by 50% of baseline values in both studies. In study I, maximal reductions in mean blood pressure occurred approximately 6 hours postdose; once-daily doses of 20 mg or greater achieved reductions of 11.3 to 21.6% (P less than or equal to .05, compared with placebo reductions). Fosinopril was well tolerated. Subjects reported only mild gastrointestinal complications at doses of 80 mg/day or higher. These data show that fosinopril is a safe and effective inhibitor of ACE with a long duration of action on serum ACE activity.
Adolescent↗
Helping nurses recognize signs of depression.
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Depressive Disorder↗
Differential expression of the c-erbB-2 gene in human small cell and non-small cell lung cancer.
We studied non-small cell lung cancers (NSCLC) from 60 patients for abnormalities in the c-erbB-2 gene. Eleven human lung cancer cell lines, including four derived from small cell lung cancer (SCLC) and seven derived from NSCLC were also examined for altered c-erbB-2 gene expression. Southern blot analysis of paired tumor and normal lung samples demonstrated that amplification of the c-erbB-2 gene is rare in NSCLC (2/60) and not restricted to adenocarcinomas. One patient showed an EcoRI restriction fragment length polymorphism for the c-erbB-2 locus. Four of four SCLC cell lines demonstrated minimal or nondetectable expression of c-erbB-2 mRNA compared to high levels of expression by seven of seven NSCLC lines. The highest expression levels were seen in four of four adenocarcinomas. We conclude that c-erbB-2 expression is different in SCLC compared to NSCLC and high expression of c-erbB-2 is consistently present in lung adenocarcinomas.
Blotting, Northern↗
Isolation and characterization of paraflagellar proteins from Trypanosoma cruzi.
Two different Trypanosoma cruzi polypeptides, with masses of 70 and 68 kDa were purified and characterized in this work. These two polypeptides designated PAR 1 and PAR 2, respectively, co-purified during each step of the isolation procedure and were found to be located exclusively in T. cruzi flagella by indirect immunofluorescence. A pre-embedding immunoelectron microscopy procedure, with a gold-tagged secondary antibody, permitted direct identification of PAR 2 as a component of the T. cruzi paraflagellar rod. PAR 1 and PAR 2 were found to be immunologically distinct and showed no cross-reactivity with actin, tubulin, intermediate filament proteins, or other proteins present in mammalian cells. The results presented indicate that PAR 1 and PAR 2 are the major components of T. cruzi paraflagellar filaments, and that these filaments have no counterpart in mammalian cells.
Animals↗
Hodgkin disease in a patient with common variable immunodeficiency.
Extensive extralymphatic Hodgkin disease developed in a young man with common variable immunodeficiency manifested by hypogammaglobulinemia, recurrent sinopulmonary infections, and multiple autoimmune phenomena. Both humoral and cell-mediated immune dysfunction were present prior to treatment. After two cycles of chemotherapy, irreversible shock developed, and death occurred secondary to overwhelming infection in spite of prophylactic gammaglobulin replacement. The unusual features of this patient's case of extralymphatic Hodgkin disease in association with a primary immunodeficiency disorder have not been previously reported.
Adult↗
Polysemy and the subjective lexicon: semantic relatedness and the salience of intraword senses.
Subjective perceptions of the senses of polysemous English words are collected in questionnaire studies and the effects of variability in semantic distances among these senses are examined in an experiment. In the first of two questionnaire studies, native speakers produce meanings for 175 polysemous words; from their responses, the most frequently produced meaning for each word is identified as its dominant sense. In a second questionnaire, independent subjects rate the semantic relatedness between the dominant meaning and the other senses generated for each word in the first study. Relatedness measures vary, raising the possibility that polysemous words vary in terms of the salience of their different senses in different contexts. This is confirmed in an experiment showing that salience ratings are influenced by the interacting factors of sentential context, extent of relatedness of the senses, and the dominance status of the senses.
Adolescent↗
Frequent nonrandom chromosome abnormalities in 27 patients with untreated large cell lymphoma and immunoblastic lymphoma.
Fresh tumor samples from 27 patients with large cell lymphoma, either previously untreated (26 patients) or minimally treated (one patient), were processed for cytogenetic studies. Cytogenetic abnormalities were observed in all patients, most commonly in chromosomes 1, 3, 7, 12, 14, 17, and 18. Nine chromosomal breakpoints appeared frequently: 14q32 in 14 instances; 18q21 in seven; 9p13-21, 17p11-13, and 3q21-23 in six each; 1p11-21 in five instances; 1p36 in four; and 2p21-23 in three. The most common structural abnormalities were t(14;18)(q32;q21) in seven patients (26%) and 17p- in six (22%). The presence of 17p- was associated with a significantly higher proliferative capacity as manifested by the percentage of S phase = 22% versus 11% for cases without 17p-(P less than 0.05). Trisomy 12, typical of small lymphocytic lymphoma, was seen in five patients in this series, all of whom had diffuse large cell lymphoma; frequently, it appeared simultaneously with t(14;18). The two patients with immunoblastic lymphoma of B-cell type had an abnormality involving chromosome 2p21-23. Deletions in the long arm of chromosome 6, previously described as typical of diffuse large cell lymphoma and B-cell immunoblastic lymphoma were observed infrequently in this series. However, this abnormality has been present in 50% of patients with large cell lymphoma previously exposed to therapy, suggesting that it may be related to effects of chemotherapy or to clonal evolution.
Chromosome Aberrations↗
Extended aortoplasty to relieve supravalvular aortic stenosis.
An extended aortoplasty was used to relieve severe supravalvular aortic stenosis in 5 patients whose preoperative left ventricular-aortic gradient ranged from 85 to 140 mm Hg (median, 120 mm Hg). The stenotic ring above the commissures was divided in two places by an inverted U incision extending into the right and noncoronary sinuses. A distal vertical incision in the ascending aorta converted this into an inverted Y. The ridge above the left coronary sinus was excised. The aortic incision was repaired with an inverted Y-shaped Dacron gusset. The postoperative gradient ranged from 0 to 30 mm Hg (median, 15 mm Hg). The extended aortoplasty provides excellent relief of supravalvular aortic stenosis and, in addition, restores the aortic root geometry to a much more anatomical configuration than is achieved with the simple patch technique.
Adolescent↗