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Biomedical subjects

N Miller

Publications and source records attributed to N Miller.

At least 91 records · Page 5Linked to original sources
PubMed1996

Selectin ligands on human melanoma cells.

Twelve established human melanoma lines were screened for surface expression of the carbohydrate antigens Lewisa (Lea), sialyl Lewisa (SLea), dimeric sialyl Lewisa (diSLea), sialyl LewisX (SLex) and dimeric sialyl LewisX (diSLeX). None of the lines expressed SLex, but 11/12 were positive for diSLeX and 7/12 were positive for SLea. Although both diSLeX and SLea have been reported to bind to E-selectin, none of the melanoma lines exhibited E-selectin-dependent adhesion to activated human umbilical vein endothelial cells (HUVECs). Three melanoma lines infected with a retroviral vector carrying the cDNA for the human Lewis fucosyltransferase (FucT-III) subsequently expressed SLeX at their cell surface and exhibited E-selectin-dependent adhesion to activated HUVECs. Treatment of these transduced cells with inhibitors of O-linked or N-linked protein glycosylation significantly inhibited E-selectin-mediated adhesion, though fluorescence-activated cell sorter analysis indicated no decrease in cell surface expression of SLeX, Slea or diSLeX. This suggests that the majority of SLeX/SLea-type glycans endogenously produced by human melanoma cells are not protein-associated and do not mediate E-selectin-dependent adhesion. These results support the hypothesis that E-selectin-dependent adhesion requires presentation of SLeX-type moieties on appropriate glycoproteins.

Carbohydrate Sequence↗
PubMed1996

Male breast cancer: an 11 year review of 66 patients.

A review was conducted of 66 men with carcinoma of the breast seen at this institution between 1981 and 1992. The results of the study suggest that there are many similarities between breast cancer in men and women. The most common clinical presentation was a lump in the breast. The majority of tumors were T1 or T2, and infiltrating ductal carcinoma was the predominant histological type. Axillary nodal status and histological grade were predictive of survival. The pattern of recurrence and survival rates were similar to those seen in women. Some differences, however, were evident. Tumors were centrally located in the majority of patients and there was a high frequency of nipple involvement. The hormone receptor positivity rate was high and the median age at presentation was older. In comparison to a previous report of the same disease from this institution 10 years ago, fewer patients underwent radical surgical procedures and more patients received adjuvant systemic therapy. These approaches are justified since there are many biological similarities between breast cancer in men and women.

Adult↗
PubMed1996

Generation of estrogen receptor mutants with altered ligand specificity for use in establishing a regulatable gene expression system.

Considerable interest exists in developing an artificial system for the control of gene expression, based on the hormone binding domain (HBD) of steroid receptors. In this study we describe a yeast based approach which allows the identification of mutations within the HBD of steroid receptors, in this case the estrogen receptor, which result in altered specificity of the HBD with respect to its activation by ligands. Using this approach in yeast, we identified an estrogen receptor (HBD) mutant (His524 to Gln) whose activation by 17 beta-estradiol (E2) is significantly reduced while activation by a diphenol indene-ol compound (GR132706X) is increased, compared to the wild type estrogen receptor. When the activity of the mutant receptor was tested in mammalian cells the altered specificity was maintained. A chimeric transcription factor was constructed, in which the mutated estrogen receptor HBD was linked to the DNA binding domain of GAL4 and an 11 amino acid transcriptional activation domain of RelA. Reporter gene activation by this chimera was decreased in response to E2 and increased in response to GR132706X, as compared to the corresponding chimeric transcription factor containing the wild type estrogen receptor HBD. This approach should allow the development of a steroid receptor HBD based regulator of gene expression, whose activity is controlled specifically by a synthetic ligand, that would not affect the activity of endogenous steroid receptors.

Amino Acid Sequence↗
PubMed1996

A prospective study comparing duplex scan and venography for diagnosis of lower-extremity deep vein thrombosis.

This study was designed to compare duplex scanning with contrast venography for the diagnosis of acute deep vein thrombosis of the lower extremity, both at the femoropopliteal (above-knee) and tibioperoneal (below-knee) levels. A total of 216 patients with 220 limbs suspected of acute deep vein thrombosis underwent duplex scanning followed within 24 h by ascending venography. The two studies were interpreted independently by two physicians who were blinded to the results of the corresponding alternative study. Venography was positive for deep vein thrombosis in 44.5% of cases (98/220). Duplex scanning was inadequate at the above-knee level in two cases (0.9%) and at the below-knee level in 17 cases (7.7%). Sensitivity and specificity of duplex scanning at above-knee level were 98.7% and 100% respectively while corresponding values were 85.2% and 99.2% at below-knee level. By excluding technically inadequate duplex studies, the sensitivity at below-knee level was clearly improved (93.8%). It is concluded that with meticulous technique, duplex scanning is highly accurate in diagnosing acute deep vein thrombosis of symptomatic lower extremities, avoiding contrast venography in over 90% of the cases, even at the tibioperoneal level.

Adult↗
PubMed1996

Learning from patients: a discharge planning improvement project.

BACKGROUND: In 1991 Beth Israel Hospital (Boston) joined nine other hospitals in using the Picker/Commonwealth survey instrument to tap patients perceptions of their hospitalization experience. Beth Israel focused on one of the nine dimensions of the instrument-continuity and transition (discharge planning). FOUR WORK TEAMS: In 1992 four multidisciplinary work teams were formed-for cardiac surgical patients, stroke patients, patients on a medical unit, and patients on a medical and surgical unit. Each team conducted a patient/family discussion group, during which recently discharged patients and their families were asked about their preparation for discharge and asked for input on how to improve the process. INTERVENTIONS: Each work team developed interventions on the basis of information specific to their patients. The cardiac work team, for example, developed interdisciplinary practice guidelines for patient care management for the entire postoperative period; the guidelines include a patient education component on what patients and families can expect during hospitalization. OUTCOMES: Clinicians practice differently, inviting more patient feedback and other involvement in care, as a results of their involvement in the project. On the first annual patient survey, administered in 1994, only 6% of 1,179 randomly selected patients (versus 20% of the 100 patients first surveyed in 1993) indicated that they did not receive the information they needed to help themselves recover. CURRENT PROGRESS AND FUTURE DIRECTIONS: A standardized teaching packet containing material developed during the discharge planning improvement project is now distributed. In May 1995 the nursing department launched a patient and family learning center to better meet the health education needs of patients.

Aftercare↗
PubMed1996

Gender differences in aggression as a function of provocation: a meta-analysis.

In this article, we meta-analytically examine experimental studies to assess the moderating effect of provocation on gender differences in aggression. Convergent evidence shows that, whereas unprovoked men are more aggressive than women, provocation markedly attenuates this gender difference. Gender differences in appraisals of provocation intensity and fear of danger from retaliation (but not negative affect) partially mediate the attenuating effect of provocation. However, they do not entirely account for its manipulated effect. Type of provocation and other contextual variables also affect the magnitude of gender differences in aggression. The results support a social role analysis of gender differences in aggression and counter A. H. Eagly and V. Steffen's (1986) meta-analytic inability to confirm an attenuating effect of provocation on gender differences in aggression.

Adult↗
PubMed1996

Alcohol and aggression: a meta-analysis on the moderating effects of inhibitory cues, triggering events, and self-focused attention.

The authors conducted a meta-analysis of 49 studies to investigate 2 explanations of how alcohol increases aggression by decreasing sensitivity to cues that inhibit it. Both the level of anxiety and inhibition conflict moderated the difference between the aggressive behavior of sober and intoxicated participants, but neither level adequately accounted for variation in effect sizes. Additional analyses of 3 social psychological moderating variables-provocation, frustration, and self-focused attention-showed that the aggressiveness of intoxicated participants relative to sober ones increased as a function of frustration but decreased as a function of provocation and self-focused attention. The authors also examined the moderating effects of dose.

Aggression↗
PubMed1996

Biallelic expression of the IGF2 gene in human breast disease.

We examined the imprinting status of the insulin-like growth factor II gene (IGF2) in a series of 20 human breast disease samples to determine if disrupted imprinting (as evidenced by biallelic expression), was a demonstrable mechanism of altered gene expression. These samples included benign (n = 7) and malignant breast lesions (n = 13). Biallelic expression of IGF2 was detectable in 67% of benign and 60% of malignant informative breast lesions. Three informative reduction mastectomies displayed normal IGF2 imprinting. The presence of this alteration in human breast tissue is a novel finding, and may contribute to tumorigenesis, possibly by favouring an enhanced proliferative milieu, during which additional mutations could occur.

Adult↗
PubMed1996

Resorption rates of 2 commercially available bioresorbable membranes. A histomorphometric study in a rabbit model.

The respective resorption rates of recently commercialized collagen versus polylactic acid-citric acid ester membranes were compared. 16 rabbits were implanted with 2 mm x 4 mm pieces of membrane of both types in the alveolar mucosa just apically to the incisors on either side of the mouth. 1 animal was sacrificed on day 0, just after the operation. The others were sacrificed at 1, 2, 3, 5, 7, 9 and 12 weeks. The specimens were prepared for histologic examination. Observations showed that the cross-linked collagen membranes induced severe inflammation and were resorbed within 2 weeks. The polylactic acid-citric acid ester polymer barriers produced a much more moderate infiltrate and were still not totally resorbed at 12 weeks. Although resorption rates in the rabbit may not be similar to those observed in humans, it seems that the durability of the polymer barrier is more adequate for guided tissue regeneration than the cross-linked collagen.

Animals↗
PubMed1996

Linkage of rheumatoid arthritis to the candidate gene NRAMP1 on 2q35.

The macrophage resistance gene NRAMP1 regulates priming/activation of macrophages for enhanced TNF alpha, IL 1 beta, and MHC class II expression. Since all of these functions are of potential importance in the induction or maintenance or both of autoimmune disease, samples from the Arthritis and Rheumatism Council's repository of multicase rheumatoid arthritis families were typed for a dinucleotide repeat in the NRAMP1 promoter region and four other 2q34 (TNP1) or 2q35 (IL8R, VIL1, DES) marker genes. Identity by descent (IBD) sib pair analysis using a three locus haplotype NRAMP1-IL8RB-VIL1, or NRAMP1 alone, provided preliminary evidence (maximum lod score = 1.01, p = 0.024) for a gene in this region contributing to suceptibility to rheumatoid arthritis. Candidacy for NRAMP1 as the disease susceptibility gene was supported by a significant bias (p = 0.048) towards transmission of the NRAMP1 promoter region allele 3 in affected offspring.

Arthritis, Rheumatoid↗
PubMed1995

Tissue-specific gene expression from Mo-MLV retroviral vectors with hybrid LTRs containing the murine tyrosinase enhancer/promoter.

Transcriptional tissue specificity was engineered directly into Moloney Murine Leukaemia Virus (Mo-MLV)-derived retroviral vectors by replacing the viral enhancer in the 3' long terminal repeat (LTR) with two different lengths (2.5 kbp or 769 bp) of the murine tyrosinase promoter/enhancer. The hybrid tyrosinase-LTR was transferred to the proviral 5' LTR following viral packaging and infection of target cell lines. Hybrid tyrosinase-LTR-driven IL-2 production was barely above background levels in infected nonmelanoma cell lines containing intact provirus, whereas infected melanoma cell lines expressed high levels of IL-2 and the larger tyrosinase promoter/enhancer fragment directed higher levels of transgene expression. By replacing the viral enhancer with the tyrosine promoter/enhancer sequences, promoter interference effects which we have previously observed when the tyrosinase promoter was included as an internal promoter within a similar retroviral vector were effectively abolished. Our data show that the hybrid tyrosinase-LTR behaves as a tightly regulated melanocytic-specific regulatory element when embedded in an enhancer-deleted Mo-MLV LTR. The use of other heterologous cellular promoter/enhancer elements in similar vectors should allow the development of simpler, targeted retroviral vectors for the expression of genes in selected cell types and may eventually provide for the development of safer, more efficient vectors for use in human gene therapy.

3T3 Cells↗
PubMed1995

A new three-dimensional treatment algorithm for complex surfaces: applications in surgery.

PURPOSE: Recent advances in computer technology enable automatic reconstruction of surface models using digitized contour lines and three-dimensional (3D) representation on a graphic terminal. This work was aimed at obtaining 3D reconstructions of facial bones to help guide oral surgery and complex dental implantology procedures. MATERIAL AND METHODS: The starting point was a computed tomographic examination. The limits of the cortical bone were automatically outlined and then digitized using a special computer program. The resulting data were then compiled for computer-aided design (CAD) purposes, and a virtual 3D model of the bone was mathematically computed. This model was next transferred to a computer program that piloted a CAD/computer-aided manufacture (CAM) machine that guided a laser stereolithography process. RESULTS: The early results of the use of 3D images, as well as solid models, for clinical and surgical purposes, indicate a high degree of reliability in morphologic diagnosis, determining the surgical procedure, and establishing the subsequent prognosis.

Algorithms↗
PubMed1995

Targeted vectors for gene therapy.

Successful gene therapy requires not only the identification of an appropriate therapeutic gene for treatment of the disease, but also a delivery system by which that gene can be delivered to the desired cell type both efficiently and accurately. Reductions in accuracy will inevitably also reduce efficiency since fewer particles will be available for delivery to the correct cells if many are sequestered into nontarget cells. In addition, the therapy will have net benefit to the patient only if gene delivery is sufficiently restricted such that normal cells are left unaffected by any detrimental affects of bystander cell transduction. Here we review how currently available delivery systems, both plasmid and viral, can be manipulated to improve their targeting to specific cell types. Currently, targeting is achieved by engineering of the surface components of viruses and liposomes to achieve discrimination at the level of target cell recognition and/or by incorporating transcriptional elements into plasmid or viral genomes such that the therapeutic gene is expressed only in certain target cell types. In addition, we discuss emerging vectors and suggest how gene therapy delivery systems of the future will be composites of the best features of diverse vectors already in use.

Adenoviridae↗