Search PubMed⌕ Search

Biomedical subjects

M Miller

Publications and source records attributed to M Miller.

At least 325 records · Page 18Linked to original sources
PubMed1996

8-Arylguanine adducts from arenediazonium ions and DNA.

Arenediazonium ions (ArN2+) are genotoxic though the source of their genotoxicity is unknown. The present studies were undertaken to determine if reductive decomposition of ArN2+ to aryl radicals (Ar) in the presence of calf thymus DNA (ctDNA) or in cells results in the formation of DNA adducts. We found that when arenediazonium ions of the general structure p-X-ArN2+ (X = CH3, CH2OCH3, CH2OH) are allowed to react with ctDNA or incubated with cells under conditions that produce p-X-Ar, DNA adducts are formed with guanine. The structure of the adduct is the C8-substitution product derived from guanine and p-X-Ar. Formation of p-X-Ar was determined by ESR spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The extent of C8-arylguanine adduction was measured by high performance liquid chromatography (HPLC) analysis of the DNA hydrosylate and comparison with authentic synthetic standards. The C8-arylguanine adducts observed to form may be important in regard to the genotoxicity of ArN2+, though other DNA adducts such as the N6-triazene of adenine or C8-aryladenine adducts can form. Finally, though the formation of C8-arylguanine adducts from arenediazonium ions has been proposed, this is the first report demonstrating their formation in DNA.

Animals↗
PubMed1996

X-linked mental retardation with thin habitus, osteoporosis, and kyphoscoliosis: linkage to Xp21.3-p22.12.

We reevaluated a family previously described as having nonspecific X-linked mental retardation (XLMR) by Snyder and Robinson [1969: Clin Pediatr 8:669-674] (MIM 309583). Clinical and DNA studies were conducted on 17 relatives, including 6 males with mild-to-moderate mental retardation, 3 carrier females, and 8 normal males. In contrast to the normal appearance and minimal clinical findings reported 22 years ago, affected males were found to have a characteristic set of clinical findings. These developed gradually over the first 2 decades, and included thin body build with diminished muscle mass, osteoporosis and kyphoscoliosis, slight facial asymmetry with a prominent lower lip, nasal speech, high narrow or cleft plate, and long great toes. Carrier females were clinically normal. Multipoint linkage analysis indicated linkage to markers distal to the 3' end of DMD (DXS41 and DXS989), with a maximal lod score of 4.7. On the basis of these findings, this entity is redefined as XLMR syndrome.

Adult↗
PubMed1996

Increased expression of IL-1beta converting enzyme in hippocampus after ischemia: selective localization in microglia.

Although the interleukin-1beta converting enzyme (ICE)/CED-3 family of proteases has been implicated recently in neuronal cell death in vitro and in ovo, the role of specific genes belonging to this family in cell death in the nervous system remains unknown. To address this question, we examined the in vivo expression of one of these genes, Ice, after global forebrain ischemia in gerbils. Using RT-PCR and Western immunoblot techniques, we detected an increase in the mRNA and protein expression of ICE in hippocampus during a period of 4 d after ischemia. Chromatin condensation was observed in CA1 neurons within 2 d after ischemia. Internucleosomal DNA fragmentation and apoptotic bodies were observed between 3 and 4 d after ischemia, a period during which CA1 neuronal death is maximal. In nonischemic brains, ICE-like immunoreactivity was relatively low in CA1 pyramidal neurons but high in scattered hippocampal interneurons. After ischemia, ICE-like immunoreactivity was not altered in these neurons. ICE-like immunoreactivity, however, was observed in microglial cells in the regions adjacent to the CA1 layer as early as 2 d after ischemic insult. The increase in ICE-like immunoreactivity was robust at 4 d after ischemia, a period that correlates with the DNA fragmentation observed in hippocampal homogenates of ischemic brains. These results provide the first evidence for the localization and induction of ICE expression in vivo after ischemia and suggest an indirect role for ICE in ischemic damage through mediation of an inflammatory response.

Animals↗
PubMed1996

Treating leg ulcers: the latest techniques.

Several advances in the care and treatment of leg ulcers are currently being developed, including laser therapy, ultrasound and the use of hyperbaric oxygen. In this article, the author describes the theory behind each therapy and the current level of research knowledge on the effectiveness and use of the methods.

Humans↗
PubMed1996

Clinical, hematologic, and biochemical features of a syndrome in Bernese mountain dogs characterized by hepatocerebellar degeneration.

Seven related Bernese Mountain Dogs developed a syndrome Characterized by progressive cerebellar and hepatic disease. Clinically, stiffness in the hind limbs, mild incoordination, and a slight head tremor were first noticeable when pups were 4 to 6 weeks old. The condition progressed, causing pups to assume a wide-based stance. Other signs included head bobbing, spontaneous nystagmus, and, finally, paresis. Hematologic findings included leukocytosis with a left shift; normocytic, normochromic anemia; hypoproteinemia, low serum creatinine, and urea nitrogen concentrations; excessive fasting plasma ammonia concentration; and an increase in concentration of serum bile acids. Portal venography performed on 1 dog revealed a small liver and extensive extrahepatic varicosities. Necropsy revealed cerebellar hypoplasia, nodular liver, extensive abdominal varicosities, and ascites. Histologically, degeneration and depletion of Purkinje's cells and vacuolation, degeneration, and nodular regeneration of hepatic tissues were evident. Preliminary analysis of the pedigree was suggestive of an autosomal recessive pattern of inheritance.

Animals↗
PubMed1996

Dexamethasone and prostaglandin E2 modulate T-cell receptor signaling through a cAMP-independent mechanism.

One possible explanation for the link between stress and increased incidence of infection can be attributed to concomitant increases in levels of glucocorticoids (GS) and prostaglandin E2 (PGE2), both of which possess potent immunoregulatory activities. We have previously demonstrated that concentrations of PGE2 and the synthetic glucocorticoid, dexamethasone (DEX), which individually do not inhibit human T-cell responsiveness to anti-CD3 monoclonal antibody (mAb), act synergistically to inhibit IL-2 secretion and subsequent T-cell proliferation. In the present paper, we demonstrate that treatment of anti-CD3 mAb-stimulated T-cells with low (10(-8) and 10(-9) M) concentrations of DEX and PGE2 results in the inhibition of steady-state levels of IL-2 mRNA. Initial studies to elucidate the biochemical mechanisms involved indicate that the inhibitory effects of DEX and PGE2 cannot be correlated with increased levels of intracellular cAMP or the induction of apoptosis. However, the data indicate that DEX and PGE2 when added together interrupt anti-CD3 mAb-induced tyrosine phosphorylation of substrate proteins. Furthermore, the synergistic effect of DEX and PGE2 is mimicked by agonists for the cAMP-independent EP3 subtype of the PGE2 receptor. These data suggest that DEX and PGE2 elicit cAMP-independent signaling pathways which interact to inhibit the T-cell receptor-linked signal transduction cascade in anti-CD3 mAb-stimulated T-cells.

Cells, Cultured↗
PubMed1996

Exposures and health effects: an evaluation of workers at a sodium azide production plant.

Sodium azide is the principal gas-generating agent used to inflate automobile supplemental restraint systems, more commonly called airbags. Although sodium azide is known to affect the cardiovascular system by causing peripheral vasodilation, there is no published literature describing occupational exposures to sodium azide in the rapidly growing automobile airbag industry. In 1994-1995, the National Institute for Occupational Safety and Health (NIOSH) conducted a cross-sectional study of health complaints reported by sodium azide production workers at the only continuous sodium azide production facility in the United States. The NIOSH evaluation consisted of a plant industrial hygiene survey, a symptom questionnaire, ambulatory blood pressure monitoring, and blood azide analysis. Personal breathing zone air monitoring revealed exposures to sodium azide and hydrazoic acid (a reactant product) at levels greater than the NIOSH Recommended Exposure Limits (RELs). In some cases, exposures exceeded the REL despite the use of air-supplied respirators. The questionnaire revealed that most workers reported headache (10 of 11 [91%]), episodes of low blood pressure (9 of 11 [82%]), and palpitations (8 of 11 [73%]) occurring in the production areas within the 6 months preceding the study. Mild headache (4 of 11 [36%]) was the only symptom reported during our 24-hr medical survey. Ambulatory blood pressure monitoring revealed one asymptomatic employee with a drop in blood pressure (defined as a drop in systolic [at least 20 mm Hg] and diastolic [at least 10 mm Hg] blood pressure) during a period of exposure to sodium azide at a level five times the NIOSH REL. Improvements in plant engineering controls, increased attention to employee hygiene practices, and a more comprehensive respiratory protection program were recommendations made by NIOSH to reduce exposures at the plant. All facilities handling sodium azide should be aware of the potential toxicity of sodium azide and hydrazoic acid.

Adult↗
PubMed1996

Comorbid anxiety disorders in late-life depression.

We examined the prevalence and correlates of comorbid anxiety disorders in two groups of older depressed patients assessed at the University of Pittsburgh. A total of 336 older outpatients and inpatients with major depression were comprehensively evaluated with several instruments including the Hamilton Depression Rating Scale, and either the SADS-L or the SCID for DSM-III-R. These patients presented with major depression, associated with a wide range of functional, cognitive, and medical impairment. One-third to one-half of them also presented with severe symptomatic anxiety. However, only a small proportion (less than 5%) met diagnostic criteria for lifetime or current panic, obsessive-compulsive, or phobic disorders. At baseline, lifetime comorbid anxiety disorders were associated with a higher rate of alcoholism and higher symptomatic anxiety. Lifetime comorbid anxiety disorders did not affect the rate of response of depression, but they were associated with a higher use of benzodiazepines and a 50% increase in the time outpatients needed to respond. These findings suggest that, even in psychiatric patients with major depression, the lifetime prevalence of anxiety disorders is lower in late life, but that it has important clinical and therapeutic implications.

Aged↗
PubMed1996

Children's performance on "animal tests" of oddity: implications for cognitive processes required for tests of oddity and delayed nonmatch to sample.

To investigate the ontogenesis of oddity learning, children (16 to 102 months of age) and adults were tested on two versions of the oddity task using non-verbal procedures originally developed for monkeys. On the standard, "one-part" or "simultaneous" oddity task (Experiment 1), young children (16 to 74 months of age) performed more poorly than older children (81-102 months of age) who were as proficient as adults. The delayed mastery of one-part oddity contrasts to mastery, at much younger ages (3 to 4 years of age) of a similar, but two-part task, delayed non-match to sample (DNMS) (Overman, 1990). In Experiment 2, those children from the first experiment who had difficulty in learning the one-part oddity task were tested on a two-part oddity task, and a subset of the subjects was retested on the one-part oddity task, and, finally, given verbal instructions for the one-part oddity task. The two-part oddity task was mastered significantly more rapidly than the previous one-part task; however, children's performance dropped significantly when tested on the one-part oddity task, and finally, children rapidly mastered the one-part oddity task when given verbal instructions. The data suggested that (a) children used different strategies to solve the different versions of the oddity task, (b) the solution for the two-part-task appeared earlier in life than the solution for the one-part task and did not involve the use of the concept of "oddity relations", and (c) in tasks in which stimuli are shown twice, behavior may come under control of the absolute properties of the exemplar stimulus via a simple "win-shift" pattern of behavior. In contrast, in tasks in which all stimuli are presented simultaneously, behavior may be controlled by stimulus relations, the analysis of which has a protracted ontogenetic development.

Adult↗
PubMed1996

Security considerations for present and future medical databases.

In this paper we consider the security of medical databases. We give an overview of the security problems and the possible available mechanisms for the prevention of security compromises. Many of the security problems are common to all databases. However, the problem of data inference from statistical queries is particularly pertinent to medical databases and consequently we treat this problem in more detail. The paper concludes with a proposal for a Security Subsystem in a database management system.

Computer Security↗
PubMed1996

Changes in plasma endothelin-1 levels reflect clinical response to beta-blockade in chronic heart failure.

Plasma levels of endothelin-1 are elevated in patients with chronic heart failure; however, it is unknown whether changes in plasma endothelin-1 levels accurately reflect clinical response to therapy in these patients. To determine this, we measured plasma endothelin-1 in addition to functional, hemodynamic, and other neurohormonal parameters as part of a double-blind, placebo-controlled study of the beta-blocker vasodilator carvedilol in patients with moderate to severe chronic heart failure. Patients were assigned (2:1 randomization) to receive carvedilol (25 mg twice daily, n = 10) or placebo (n = 5) for 14 weeks, with evaluations made before and after therapy. Compared to patients receiving placebo, patients receiving carvedilol improved significantly as assessed by the parameters described. These changes were paralleled by significant falls in endothelin-1 with carvedilol (-2.1 + 3.8 pg/ml) in comparison to placebo (2.2 + 3.9 pg/ml; p < 0.05 for between-group differences). Changes in endothelin-1 after treatment in both groups correlated significantly with changes in symptom severity, New York Heart Association class, 6-minute walk distance (r = 0.64 to 0.80; p < 0.05), hemodynamic parameters (ejection fraction, right atrial pressure, pulmonary artery diastolic pressure, pulmonary wedge pressure, right atrial pressure, and stroke volume index; r = 0.54 to 0.86; p < 0.05), and neurohormonal parameters (serum aldosterone and plasma norepinephrine (r = 0.74 to 0.76; p < 0.05). By stepwise regression analysis, change in endothelin-1 was an independent, noninvasive predictor of functional and hemodynamic responses to therapy in these patients. These findings suggest that endothelin-1 accurately reflects functional, hemodynamic, and neurohormonal responses to beta-blocker therapy in patients with congestive heart failure. Measurement of endothelin-1 may therefore be a useful, noninvasive approach to the evaluation of clinical response to drug therapy in these patients.

Adrenergic beta-Antagonists↗
PubMed1996

Extravesical ureteral reimplantation: results in 128 patients.

PURPOSE: We evaluated the results of extravesical ureteral reimplantation in children. MATERIALS AND METHODS: We reviewed the records of 128 children (174 ureters) who underwent ureteral reimplantation via extravesical techniques. Primary vesicoureteral reflux was the most common diagnosis (73 patients). RESULTS: The extravesical technique produced a successful result in all patients (no reflux or obstruction). The 2 complications included postoperative urosepsis and transient urinary retention. CONCLUSIONS: Extravesical ureteral reimplantation is a reliable procedure with predictable results comparable to those of more traditional intravesical techniques.

Adolescent↗
PubMed1996

Making information accessible: developing plain English discharge instructions.

Discharge education has always been an important role for nurses working in acute care contexts. With the advent of case mix funding and subsequent trends towards early discharge from hospital, this educational role is assuming increasing importance. This paper addresses one aspect of a participatory action research study where a group of nurses, working in a paediatric orthopaedic ward, explored their discharge education practices and resources. The seemingly large number of post-discharge telephone queries received from parents of children treated on the ward prompted these nurses to question whether their discharge teaching practices were effective. Data collected on these telephone queries identified parental concerns regarding the care of their child at home in a plaster. This finding prompted group members to explore the ways that written information relating to care of the plaster at home might be implicated in the situation. An analysis of an existing 'home cast care' discharge instruction sheet raised issues concerning the content and language used in such resources. The paper describes the subsequent development of a plain English 'plaster care' discharge instruction sheet and argues the importance of using plain English in such resources.

Child↗
PubMed1996

Gastric toxoplasmosis in acquired immunodeficiency syndrome: antemortem diagnosis with histopathologic characterization.

Gastrointestinal symptoms attributable to Toxoplasma gondii infection are distinctly unusual, and antemortem diagnosis of gastrointestinal involvement is rarely documented, particularly in the absence of cerebral manifestations or disseminated disease. This case report describes a rare example of T. gondii infection of the stomach diagnosed antemortem in a 22-year-old Haitian woman with acquired immunodeficiency syndrome (AIDS) who presented with fever and abdominal pain. An abdominal computerized tomographic scan showed thickened gastric walls. Endoscopy showed diffusely thickened gastric folds and a fundic ulcer along the greater curvature. Light and electron-microscopic examination of gastric mucosal biopsy specimens showed active Toxoplasma infection with necrosis and intracellular trophozoites within the gastric epithelium, smooth muscle cells, macrophages, and endothelial cells. Both true cysts and pseudocysts were seen. Disseminated disease was documented by the growth of T. gondii in a tissue culture from a venous blood sample. It is concluded that some patients with AIDS, particularly those from areas endemic for Toxoplasma infection, can manifest disseminated disease in unusual locations such as the gastrointestinal tract. Documentation of active T. gondii infection based on tissue cultures of venous blood or on biopsy specimens of symptomatic extracerebral sites can lead to a rapid diagnosis of toxoplasmosis, a treatable disease.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Duplicated proteasome subunit genes in Drosophila melanogaster encoding testes-specific isoforms.

Using the previously cloned proteasome alpha-type subunit gene Pros28.1, we screened a Drosophila melanogaster genomic library using reduced stringency conditions to identify closely related genes. Two new genes, Pros28.1A (map position 92F) and Pros28.1B (map position 60D7), showing high sequence similarity to Pros28.1, were identified and characterized. Pros28.1A encodes a protein with 74% amino acid identity to PROS28.1, while the Pros28.1B gene product is 58% identical. The Pros28.1B gene has two introns, located in exactly analogous positions as the two introns in Pros28.1, while the Pros28.1A gene lacks introns. Northern blot analysis reveals that the two new genes are expressed only in males, during the pupal and adult stages. Tissue-specific patterns of expression were examined using transgenic flies carrying lacz-fusion reporter genes. This analysis revealed that both genes are expressed in germline cells during spermatogenesis, although their expression patterns differed. Pros28.1A expression is first detected at the primary spermatocyte stage and persists into the spermatid elongation phase of spermiogenesis, while Pros28.1B expression is prominent only during spermatid elongation. These genes represent the most striking example of cell-type-specific proteasome gene expression reported to date in any system and support the notion that there is structural and functional heterogeneity among proteasomes in metazoans.

Amino Acid Sequence↗
PubMed1996

Large outbreak of pertussis among young children in Chicago, 1993: investigation of potential contributing factors and estimation of vaccine effectiveness.

BACKGROUND: An outbreak of pertussis from July, 1993, to April, 1994, in Chicago was investigated to identify potential contributing factors. METHODS: Surveillance was enhanced to identify cases. Information from a vaccination coverage survey was used to define a retrospective cohort to estimate vaccine effectiveness of three or more doses of pertussis vaccine. RESULTS: The median age of 218 reported cases was 8 months, 46% had Hispanic surnames and cases were clustered geographically. Vaccination status was known for 173 of 191 (91%) children younger than 6 years of age. Of these 173, 90 (52%) were younger than 7 months, and 35 (20%) children at least 7 months of age had received fewer than 3 doses of pertussis vaccine. Pertussis vaccine effectiveness was 76% (95% confidence interval, 29 to 92). CONCLUSIONS: The limited ability of the current pertussis vaccination schedule to protect young infants accounted for 52% of cases, primary vaccine failure accounted for 28% of cases and failure to vaccinate children on time accounted for 20% of cases in young children. Low vaccine effectiveness did not appear to be a contributing factor.

Causality↗
PubMed1996

Pharmacological characterization of the inwardly-rectifying current in the smooth muscle cells of the rat bladder.

1. In freshly-isolated single cells of the rat bladder detrusor, outwardly-rectifying and inwardly-rectifying membrane currents were identified by the whole-cell voltage-clamp technique. 2. The inwardly-rectifying current (IIR) exhibited features of a cation current permeable to both K+ and Na+ but it was unaffected by changes in extracellular Ca2+. It had an activation threshold close to -60 mV and an estimated reversal potential of -29 mV. 3. IIR activated slowly with a voltage-sensitive time-constant of 69 ms at -140 mV and 209 ms at -100 mV but did not exhibit time-dependent inactivation. 4. IIR was unaffected by tetraethylammonium (up to 20 mM) but it was reduced by extracellular Ba2+ (1 mM) and by extracellular Cs+ (1 mM). 5. IIR was reduced by terikalant (100 microM) and markedly inhibited by ciclazindol (100 microM) although at these concentrations, both agents also reduced outward currents. 6. IIR was inhibited by ZD7288 (10-100 microM) in a concentration-dependent manner. At concentrations up to 30 microM, ZD7288 did not reduce the magnitude of outward currents but these were inhibited by 100 microM ZD7288. 7. In strips of bladder detrusor, spontaneous mechanical activity was increased by ZD7288 (0.3-100 microM) and by ciclazindol (0.3-100 microM) but was unaffected by glibenclamide (1-10 microM). 8. It is concluded that IIR closely resembles the hyperpolarization-activated current Ih, previously described in the smooth muscle of rabbit jejunum and in a variety of other cell types. This current may play an important role in modulating detrusor excitability but this could not be confirmed using the inhibitors ZD7288 and ciclazindol.

Animals↗