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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 217 records · Page 12Linked to original sources
PubMed1996

The chemical reactivity and structure of collagen studied by neutron diffraction.

The chemical reactivity of collagen can be studied using neutron diffraction (a non-destructive technique), for certain reaction types. Collagen contains a number of lysine and hydroxylysine side chains that can react with aldehydes and ketones, or these side chains can themselves be converted to aldehydes by lysyl oxidase. The reactivity of these groups not only has an important role in the maintenance of mechanical strength in collagen fibrils, but can also manifest pathologically in the cases of aging, diabetes (reactivity with a variety of sugars) and alcoholism (reactivity with acetaldehyde). The reactivity of reducing groups with collagen can be studied by neutron diffraction, since the crosslink formed in the adduction process is initially of a Schiff base or keto-imine nature. The nature of this crosslink allows it to be deuterated, and the position of this relatively heavy scattering atom can be used in a process of phase determination by multiple isomorphous replacement. This process was used to study the following: the position of natural crosslinks in collagen; the position of adducts in tendon from diabetic rats in vivo and the in vitro position of acetaldehyde adducts in tendon.

Acetaldehyde↗
PubMed1996

Immunoregulatory effects of interferon-beta and interacting cytokines on human vascular endothelial cells. Implications for multiple sclerosis autoimmune diseases.

The mechanism(s) of action responsible for the anti-inflammatory effects mediated by interferon (IFN)-beta are still elusive although suggestions include anti-viral effects, the enhancement of natural killer (NK) or suppressor T cell activity and opposition to the effects of inflammatory cytokines. As vascular endothelial cells are active participants in inflammatory and demyelinating processes, we decided to examine the effects of IFN-beta on the expression of major histocompatibility complex (MHC) gene products and intercellular adhesion molecule (ICAM)-1 on human vascular endothelial cells (ECs). Human umbilical ECs demonstrated constitutive expression of ICAM-1 and MHC class I molecules but did not express MHC class II molecules. Basal expression of ICAM-1 molecules was enhanced by TNF alpha and to a lesser extent by IFN-beta, but was not affected by IFN-gamma. MHC class I expression on ECs was enhanced by IFN-beta, IFN-gamma, and tumor necrosis factor (TNF)-alpha. Furthermore, a synergistic effect was observed to combinations of these interacting cytokines. Incubation of ECs with IFN-gamma, but not IFN-beta, induced class II expression in a dose dependent manner. Moreover, co-incubation of ECs with IFN-beta and IFN-gamma resulted in significant down-regulation of class II molecules expression which was directly dependent on IFN-beta concentration. Northern blot analysis of DR alpha and Beta 2-microglobulin mRNA expression suggested that cytokine-mediated regulation of MHC molecules is at the transcriptional level, while modulation of ICAM-1 expression appears to be at the transcriptional as well as post-transcriptional level. Thus, our study demonstrated that IFN-beta and interacting cytokines exert complex immunoregulatory effects on endothelial cells with differential modulatory effects on various cell surface markers. Understanding the biological significance of these immunomodulatory effects mediated by IFN-beta may have important implications for cytokine-based strategies in the treatment of inflammatory and autoimmune diseases.

Autoimmune Diseases↗
PubMed1996

Application of the Roche Amplicor Mycobacterium tuberculosis (PCR) test to specimens other than respiratory secretions.

The ability of the Roche AMPLICOR Mycobacterium tuberculosis (MTB) test to detect M. tuberculosis in specimens other than respiratory secretions was evaluated. A total of 249 specimens from 219 patients were tested. Of these, 12 specimens grew isolates of the M. tuberculosis complex and four grew isolates of the M. avium complex. The AMPLICOR MTB test was positive for 10 of the 12 specimens which grew M. tuberculosis and for three specimens which were culture negative. Two of the latter specimens were from patients with a clinical diagnosis of tuberculosis and with multiple sputum specimens which grew M. tuberculosis. Four specimens grew M. avium complex isolates, and all yielded negative AMPLICOR MTB test results. The sensitivity, specificity, and positive and negative predictive values for the AMPLICOR MTB test were 85.7%, 99.5%, 92.3%, and 99.1%, respectively. Our data indicate that the AMPLICOR MTB test will permit the rapid detection of M. tuberculosis in specimens other than respiratory secretions.

Biopsy↗
PubMed1996

Alterations in apolipoprotein E expression during aging and neurodegeneration.

Apolipoprotein E (apoE) is a 34 kDa protein that plays an important role in cholesterol transport, uptake and redistribution. Within the nervous system, apoE might be involved in maintaining synaptic integrity after injury and during aging. ApoE might help maintain the integrity of the synaptodendritic complex by several different mechanisms. Among them, recent studies have suggested that apoE: (1) stabilizes the neuronal cytoskeleton; (2) plays an important role in transporting esterified cholesterol to neurons undergoing reinnervation where it is taken up by the low density lipoprotein receptor-related protein pathway and used as a precursor for the synthesis of new synaptic terminals; (3) regulates interactions between neurons and the extracellular matrix (e.g. laminin); and (4) regulates levels of intracellular calcium. The main objective of the manuscript is to review the current progress in understanding the functions of apoE in the nervous system and how malfunctioning of this molecule might result in neurodegenerative disorders such as Alzheimer's disease.

Aging↗
PubMed1996

Results of a policy with arm veins used as the first alternative to an unavailable ipsilateral greater saphenous vein for infrainguinal bypass.

PURPOSE: Aggressive policies for distal bypass and coronary revascularization increase the need to identify alternatives to autologous saphenous vein grafts. We examined the performance of arm vein as the primary alternative to contralateral saphenous vein when the ipsilateral saphenous vein was not available. METHODS: A total of 250 arm vein grafts were studied retrospectively in 224 patients (143 men, 81 women, 82.6% with diabetes, mean age 68.3 years) from February 1989 to April 1994. Intraoperative angioscopy was carried out to observe valve lysis, remove abnormalities, and select optimal vein segments. RESULTS: A total of 85 primary, 103 repeat, and 62 graft revision procedures were done for limb salvage in 99.2% of the patients. A total of 41 femoropopliteal, 114 femorotibial-pedal, 33 popliteodistal, and 62 jump or interposition grafts were constructed. A total of 199 grafts were single vein, and 51 were composite vein. The source was cephalic vein alone in 50.4%, cephalic and basilic vein in 35.6%, and basilic vein only in 14%. The contralateral saphenous vein as an alternative conduit was available in 97 (38.8%) instances. Interventions guided by angioscopy to "upgrade" the graft were necessary in 51.6%. Overall early patency (< or = 30 days) was 94.8% (n = 13 occlusions). The cumulative primary patency rate at 1 year was 70.6%, the secondary patency rate was 76.9%, and the limb salvage rate was 88.2%. The 3-year patency rate (limb salvage) was 51.9% (92.4%) for primary grafts, 56.7% (67.1%) in revision grafts, and 42.4% (79.9%) in repeat grafts. In 22.7% (22 of 97) the available contralateral saphenous vein was used for distal revascularization within the follow-up period. CONCLUSIONS: Arm veins are an easily accessible autologous conduit of sufficient length to reach the midtibial level. Excellent patency rates allow durable limb salvage in otherwise difficult circumstances. Vein configuration and splicing do not affect patency rates, but vein quality and repeat operations do. Angioscopy is a valuable adjunct to upgrade graft quality. The contralateral saphenous should be saved for subsequent contralateral revascularization or coronary artery bypass grafting.

Adult↗
PubMed1996

Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2.

The first crystal structure of human cyclooxygenase-2, in the presence of a selective inhibitor, is similar to that of cyclooxygenase-1. The structure of the NSAID binding site is also well conserved, although there are differences in its overall size and shape which may be exploited for the further development of selective COX-2 inhibitors. A second COX-2 structure with a different bound inhibitor displays a new, open conformation at the bottom of the NSAID binding site, without significant changes in other regions of the COX-2 structure. These two COX-2 structures provide evidence for the flexible nature of cyclooxygenase, revealing details about how substrate and inhibitor may gain access to the cyclooxygenase active site from within the membrane.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Collagen alteration in an animal model of colonic diverticulosis.

BACKGROUND: Changes in the structure and integrity of the colon dependent on collagen content and crosslinkage occur with age. AIMS: This study using an animal model examines colonic collagen content and crosslinkage over the lifetime of rats on fibre deficient and higher fibre diets. METHODS: Two groups of 20 rats were fed either a fibre deficient diet (1.7 g NSP (non-starch polysaccharide)/100 g) or a higher fibre diet (13.3 g NSP/100 g) for 18 months. Diverticula were identified by postmortem examination. Caecal and colonic contents were weighed and assayed for short chain fatty acids. Collagen solubility in weak acid was measured to give an indication of the nature and amount of crosslinks in the collagen of the bowel wall. RESULTS: The incidence of colonic diverticula was greater (42.1% fibre deficient rats; 0% higher fibre rats). Colonic collagen solubility index in fibre deficient rats was significantly lower than higher fibre diet fed rats (p < 0.001 in all four sections of the large bowel). Rats with diverticula had the lowest solubility index (p < 0.001 in all four sections of the large bowel). Higher fibre diet rats had increased caecal and colonic contents, caecal and colonic tissue wet weights, and greater caecal short chain fatty acids. Fibre deficient diet fed rats had more pathological abnormalities. CONCLUSIONS: This animal model permits a study of the relation between collagen crosslinkage and the development of colonic diverticulosis. A higher fibre diet protects against collagen crosslinking and this is related to a decreased incidence of diverticula.

Aging↗
PubMed1996

An association between maternal diet and colonic diverticulosis in an animal model.

BACKGROUND/AIMS: Maternal diet may have an effect on the health of the offspring in middle and later life. This study used the laboratory rat as an animal model to examine whether the fibre content of the maternal diet during pregnancy affected subsequent development of colonic diverticula in the offspring fed lifelong fibre deficient or higher fibre diets. METHODS: The parents of experimental animals were fed either a diet that was known to predispose to colonic diverticulosis or a control diet for one month prior to mating. The offspring were fed one of these diets for 18 months. The incidence of colonic diverticulosis, submucosal collagen content, collagen solubility in weak acid, and the composition of intestinal contents were then measured. RESULTS: Offspring of rats fed a higher fibre diet from higher fibre diet fed parents had 0% incidence of colonic diverticulosis. When offspring (regardless of parental diet) were fed a low fibre diet for life the acid solubility was lowered compared with rats fed lifelong higher fibre diet mean (SD) (0.044 (0.0007) v 0.073 (0.0015) sigmoid colon (ratio of soluble:insoluble collagen)); 21.1% had diverticulosis and there was reduced fibre fermentation. However, when the diet of the parents of the fibre deficient diet fed rats was considered, the animals whose mothers had a fibre deficient diet had lower acid solubility (0.032 (0.0007)) and an increased incidence of colonic diverticulosis (42.1%) than the animals fed a fibre deficient diet from higher fibre diet fed parents (p < 0.01 in all instances). CONCLUSION: Maternal diet and the subsequent nutrition of the progeny seem to be of importance in the development of colonic diverticulosis in the rat.

Animals↗
PubMed1996

Relation of spirometric function to radiographic interstitial fibrosis in two large workforces exposed to asbestos: an evaluation of the ILO profusion score.

OBJECTIVES: To analyse quantitatively the relations of spirometric lung function (forced vital capacity (FVC)) to radiographic interstitial pulmonary fibrosis (assessed by the International Labour Organisation (ILO) profusion score of small irregular opacities) in two large workforces exposed to different intensities of asbestos. These analyses consider the question whether a similar profusion score n differently exposed workers is associated with a similar effect on lung function. METHODS: Surveys of two workforces, insulators (n = 2611) and sheet metal workers (n = 1245), by the same investigators allowed comparison of the effects of the two levels of exposure to asbestos. The two groups were of similar age and had similar percentages of non-smokers and smokers. All radiographs were read by the same expert reader. RESULTS: Consistent with their less continuous and less intense exposure to asbestos, metal workers had: (a) far less frequent radiographic asbestosis (profusion score > or = 1/0, 17.5% v 59.6% for insulators): (b) less severe radiographic asbestosis (only 1.1% had scores > or = 2/1 v 13.3% of insulators); (c) a similar slope to that seen in insulators for the relation between FVC and profusion score when pleural thickening was absent; (d) less frequent pleural fibrosis (36% v 75%); and (e) less frequent restrictive impairment (23% v 33%). In both insulators and metal workers, lung function was below normal even when lung fields were normal, FVG fell with increasing profusion, it was lower in smokers and in those with pleural thickening at comparable profusion scores, and these was no difference in FVC between scores 0/1 and 1/0. CONCLUSION: The decrease in FVC with increasing profusion score in both workforces as well as the similar slopes for the relation between FVG and profusion score and the similar FVG at similar scores in the absence of pleural thickening confirm the ILO profusion score as an acceptable assessment of pulmonary fibrosis.

Adult↗
PubMed1996

Relationship among cellular diacylglycerol, sphingosine formation, protein kinase C activity, and parathyroid hormone secretion from dispersed bovine parathyroid cells.

To separate the role of changes in parathyroid diacylglycerol (DG) from other effects of extracellular calcium, we studied the effect of inhibition of DG metabolism on PTH secretion and cellular DG content in acutely dispersed bovine parathyroid cells. R 59 022, an inhibitor of DG kinase, increased cellular DG, but significantly decreased PTH secretion. Particulate protein kinase C (PKC) activity decreased in bovine parathyroid cells incubated at high extracellular calcium or in the presence of R 59 022, which is the opposite of what was observed in the presence of the phorbol ester, phorbol myristate acetate. Sphinganine, a normal cellular product that is a known inhibitor of PKC, significantly inhibited PTH secretion at low extracellular calcium, but had no significant effect at normal or high extracellular calcium. We then measured sphingosine in bovine parathyroid cells incubated with high extracellular calcium or R 59 022. Both conditions were associated with significant elevations of cellular sphingosine. These studies suggest that inhibition of PTH secretion and PKC activity by enhanced cellular DG may result from the activation of an inhibitory second messenger pathway involving the sphingoid lipids.

Animals↗
PubMed1996

Peroneal tenosynovitis following acute gonococcal infection.

A 17-year-old adolescent girl presented with tenosynovitis of the peroneal tendons following diagnosis and treatment of an endocervical gonococcal infection. The need for careful history in any sexually active adolescent is emphasized. Acute peroneal tenosynovitis, although not previously cited in the literature, can occur and should be suspected.

Acute Disease↗
PubMed1996

Double-blind comparison of 2.5 and 5.0 mg of prostaglandin E2 gel for preinduction cervical ripening.

OBJECTIVE: To compare the effectiveness and safety of 2.5 vs. 5.0 mg of prostaglandin E2 (PGE2) gel for preinduction cervical ripening. STUDY DESIGN: Patients presenting for induction of labor with an unfavorable Bishop score (< or 4) were assigned randomly, in a double-blind manner, to receive either 2.5 or 5.0 mg of PGE2 gel intravaginally. A repeat Bishop score was determined in four to six hours, and if the score was still unfavorable, the same dose of gel was administered a second time. All patients returned within 12 hours for induction of labor. RESULTS: A total of 119 patients received PGE2 gel, 55 in the 2.5-mg group and 64 in the 5.0-mg group. Both groups were similar with respect to age, parity, race, indication for induction and preinduction Bishop score. Both doses of PGE2 gel were safe and effective. The need for additional doses of gel, the need for and duration of oxytocin use, and the duration of labor were similar in both groups. More infants whose mothers received the 5.0-mg dose had one-minute Apgar scores < 7 (P = .027). No significant difference in five-minute Apgar scores was noted. Cesarean delivery for failed induction was uncommon, occurring in 3.6% of patients who received 2.5 mg and in 4.7% of patients who received 5.0 mg of PGE2 gel (P = NS). Finally, the incidence of hyperstimulation was 3.6% in the 2.5-mg group and 1.6% in the 5.0-mg group (P = NS). CONCLUSION: A 5-mg dose of PGE2 gel was neither more effective nor associated with more side effects than the more commonly used 2.5-mg dose.

Administration, Intravaginal↗
PubMed1996

Risk analysis in the valuation of medical practices.

Risk analysis techniques used in valuing medical practices are discussed. Employing these techniques provides superior information to the analyst than using a single estimate for uncertain variables. Examples of scenario analysis, sensitivity analysis, and simulation are presented. These tools can be easily implemented with spreadsheet software.

Computer Simulation↗
PubMed1996

The enemy within: diarrheal rates among British and Australian troops in Iraq.

British and Australian medical teams working in Northern Iraq in 1991 providing primary care to refugees and the war wounded were subjected to a descriptive retrospective survey, 5 weeks after arriving in Iraq. The aim was to document different rates of diarrhea in British and Australian troops. The British, who were not taking daily doxycycline and did not enforce a plate- and hand-washing routine, experienced higher rates of diarrhea (69% of British troops compared with 36% of Australian troops), which was more severe and of a longer duration (p < 0.001) and resulted in twice as many days being lost (p < 0.001) in spite of the British team being half the size of the Australian contingent, and the region having enteropathogens with a high rate of antibiotic resistance. Vigorous hand- and plate-washing routines along with doxycycline prophylaxis appear to significantly reduce incapacitation from diarrhea in this military setting and have an important implication for operational effectiveness.

Anti-Bacterial Agents↗
PubMed1996

Vulnerability of multidrug-resistant tumor cells to the aromatic fatty acids phenylacetate and phenylbutyrate.

Cytotoxic chemotherapies often give rise to multidrug resistance, which remains a major problem in cancer management. In pursuit of alternative treatments for chemoresistant tumor cells, we tested the response of multidrug-resistant (MDR) tumor cell lines to the aromatic fatty acids phenylacetate (PA) and phenylbutyrate (PB), two differentiation inducers currently in clinical trials. Both compounds induced cytostasis and maturation of multidrug-resistant breast, ovarian, and colon carcinoma cells with no significant effect on cell viability. In contrast to their poor response to doxorubicin, the MDR cells were generally more sensitive to growth arrest by PA and PB than their parental counterparts. The aromatic fatty acids, like the differentiation-inducing aliphatic fatty acid butyrate, up-regulated mdr-1 gene expression. However, while butyrate increased multidrug resistance, PA and PB potentiated the cytotoxic activity of doxorubicin against MDR cells. The latter was associated with time-dependent declines in glutathione levels and in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, the antioxidant enzymes implicated in cell resistance to free radical-based therapies. Taken together, our in vitro data indicate that PA and PB, differentiation inducers of the aromatic fatty acid class, may provide an alternative approach to the treatment of MDR tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Identification, cloning, and characterization of the bacteriophage N4 gene encoding the single-stranded DNA-binding protein. A protein required for phage replication, recombination, and late transcription.

The coliphage N4-coded single-stranded DNA-binding protein (N4SSB) is essential for phage replication and for expression of the phage late genes, which are transcribed by the Escherichia coli sigma 70 RNA polymerase. As a first step in investigating the role of N4SSB in replication and transcriptional activation, we have identified and sequenced the N4SSB gene. The gene encodes a 265-amino acid protein with no apparent sequence homology to other single-stranded DNA-binding proteins. We present data indicating that N4SSB is also essential for phage recombination. Mutational analysis of the carboxyl terminus of the protein indicates that this region is required for protein-protein interactions with the N4 replication, N4 recombination, and E. coli transcriptional machineries, while the rest of the protein contains the determinants for single-stranded DNA binding.

Amino Acid Sequence↗