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Biomedical subjects

S Mann

Publications and source records attributed to S Mann.

At least 37 records · Page 2Linked to original sources

Identification of differentially expressed genes in organ-confined prostate cancer by gene expression array.

BACKGROUND: To understand the molecular mechanisms underlying prostate cancer, we have utilized the gene expression array to search for genes whose expression is altered in this disease. METHODS: RNA quality from manual microdissected tissue was compared with that from microselected tissue by electrophoresis. For array analysis, malignant and normal prostate epithelium was enriched using microselection technique from prostate cancer and the peripheral zone of a normal prostate. Identical array membrane was hybridized to labeled cancer and normal cDNA, respectively. The differentially expressed gene was further evaluated by RT-PCR. RESULTS: Microdissection, but not microselection, causes visible degradation to RNA. Of the 588 genes on the membrane, 87 genes yielded significant signals. Based on a three fold difference relative to normal prostate tissue, 1 gene was overexpressed and 12 genes underexpressed in prostate cancer. Of them, five showed statistically significant reduction in mRNA levels in six prostate cancer specimens compared with seven normal prostate specimens. These five genes are glutathione S-transferase M1 (GSTM1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha receptor-1 (TNFR-1), transforming growth factor beta3 (TGF-beta3), and inhibitor of DNA binding-1 (ID-1). CONCLUSIONS: GST-based metabolism, cytokine MCP-1 and TNFR-1, and TGF-beta3 signaling pathways, and some helix-loop-helix nuclear proteins could be potentially important in organ-confined prostate cancer and deserve further investigation.

Adult↗

Chromosomal positioning of human T-lymphotropic type 1 proviruses by fluorescence in situ hybridisation.

Fluorescence in situ hybridisation (FISH) was employed to identify the chromosomal integration site of the human T-cell lymphotropic virus, type 1 (HTLV-1) present in T-cell clones derived from HTLV-1-infected individuals and a virally transformed cell line, C8166-45. Proviral sequences were detected in C8166-45 but not uninfected Jurkat cells. Integration sites were reliably detected in T-cell clones determined previously to be infected with HTLV-1. The results indicated that the transformed cell line and some of the T-cell clones possessed more than one proviral integration site. This hybridisation system is useful for determining the number of integration events and for localising proviruses to specific chromosomal regions.

Cell Line, Transformed↗

Circulating factors may be responsible for murine strain-specific responses to mobilizing cytokines.

OBJECTIVE: To determine if circulating factors influence strain-specific responses to administration of hematopoietic stem-cell mobilizing cytokines, a murine model was employed. METHODS: Plasma aliquots from intact DBA2, Balb/c, and C57Bl/6 mice were injected into intact Balb/c mice prior to delivery of mobilizing cytokines. Control Balb/c mice were injected with mobilizing cytokines alone. Plasma from hemi-body irradiated Balb/c mice, known to inhibit mobilization, was also injected into Balb/c mice. Twenty-four hours later, spleen cells were harvested and assayed for granulocyte-macrophage colony-forming cells (GM-CFC) and high-proliferative-potential colony-forming cells (HPP-CFC). Simultaneously harvested blood aliquots were assayed for CD45(+)/CD34(+) cells using flow cytometric techniques. RESULTS: Mice receiving plasma from any source demonstrated significant inhibition of mobilization of HPP-CFC and GM-CFC to the spleen as compared to mobilized controls; for HPP-CFC, plasma from C57Bl/6 mice was more inhibitory than plasma from Balb/c (p = 0.001) or from DBA2 mice (p = 0.01), while for GM-CFC, plasma from C57Bl/6 mice was more inhibitory than Balb/c plasma but not more inhibitory than DBA2 plasma. Mice injected with plasma from previously irradiated Balb/c mice exhibited the expected HPP-CFC and GM-CFC mobilization inhibition, which was not statistically different from the inhibition seen in animals that received C57Bl/6 plasma. Mobilization of CD34(+)/CD45(+) cells to the blood also appeared to be inhibited by pretreatment with C57Bl/6 plasma, but not DBA2 plasma. CONCLUSION: These data suggest that strain-specific patterns of mobilization may be influenced by a circulating mobilization inhibitor(s).

Animals↗

The medical interview: differences between adult and geriatric outpatients.

BACKGROUND: There is a perception that primary care physicians spend less time with older patients and little is known about physician and older patient satisfaction during clinical encounters. OBJECTIVE: To determine how primary care interviews of geriatric patients differ from those of other adults. DESIGN: Descriptive, analytic study. SETTING: Ten primary care sites in the United States and one in Canada, including public, voluntary, and private clinics and practices. PARTICIPANTS: Of the 544 patients, 45.6% were 65 and older and 17.8% were 75 or older. There were 127 participating physicians. MEASUREMENTS: Encounters were audiotaped and analyzed. Patients and physicians also completed exit questionnaires. RESULTS: Interview length increased significantly with age for men but not for women. Physician satisfaction did not change as patient age increased. Patient satisfaction, on the other hand decreased with age among women but not for men. Although physicians' and younger patients' perceptions of health were moderately associated, there was no association for men ages 75 and over. CONCLUSIONS: There is no evidence that physicians spend less time or are more uncomfortable with older patients. Both physician and male patient satisfaction remain stable with increasing patient age, despite greater disparity in patient and physician perceptions of health. Older female patients are less satisfied with physician visits than their younger counterparts, in the absence of changes in interview length or disparities between older female patients and their physicians in health perception.

Adult↗

Estrogen receptor beta expression in invasive breast cancer.

The aim of this work was to determine the extent of estrogen receptor beta (ER-beta) expression in invasive breast cancer (BrCA) and whether ER-beta expression is correlated with response to adjuvant hormonal therapy with tamoxifen (AHTT). Immunohistochemical staining (IHC) for estrogen receptor alpha (ER-alpha) and ER-beta was performed on sections of formalin-fixed and paraffin-embedded tissue from 47 unselected invasive breast carcinomas (BrCA). IHC for ER-beta was also performed on sections of BrCA from 118 women who were treated with mastectomy and AHTT. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. Of the 47 unselected BrCA, 17 (36%) were negative for ER-alpha and of these, 8 (47% of ER-alpha negative cases and 17% of all 47 patients) were ER-beta positive. Five of the 8 ER-alpha negative and ER-beta positive cases were positive for ER biochemically. There was no correlation between ER-beta positivity and overall survival in the unselected group. By contrast, in the group of women treated with AHTT, expression of ER-beta in more than 10% of cancer cells was associated with better survival (P = .0077), even in women with node-negative BrCA (P = .0069). In conclusion, our results show that a significant number of women with BrCA are positive for ER-beta only, and may be determined to be ER-negative when currently available IHC is used. ER-beta status is a significant predictor of response to AHTT in women with BrCA. Larger studies with multivariate analysis are needed to confirm these findings.

Blotting, Western↗

[Possibilities and limits of interventional therapy in necrotizing pancreatitis].

We present a new technique for minimal invasive radiological assisted necrosectomy (MIRAN) for infected necrosis in acute pancreatitis. We describe how to place volumic catheters for fragmentation and extraction of necrotic material. In addition a new technique is described for minimal invasive occlusion of selected pancreas tail to avoid fistulas. In 26 patients with infected necrosis of the pancreatic region, 12 patients (46.2%) could be healed by MIRAN alone. 5 patients (19.2%) could be satisfactory treated with a combination of MIRAN and operative necrosectomy. 9 patients (34.6%) died, 5 of them postoperatively. In 7 cases death followed multiple organ failure/dysfunction syndrome. 12 (71%) of 17 patients with the aim of curative treatment could be satisfactory treated with MIRAN. 2 other patients (12%) received additional surgery, 3 patients died (17%), 2 of them without any other treatment. The advantages of MIRAN are reduced trauma, general anaesthesia is not necessary, no difficult surgical preparation is necessary, no limits for additional therapy, reduced damage of neighbouring organs and vital pancreatic tissue as well as avoiding splenectomy.

Cause of Death↗

New-onset palpitations in general practice: assessing the discriminant value of items within the clinical history.

BACKGROUND: Palpitations are non-specific, with less than half of patients experiencing palpitations having a cardiac arrhythmia. Currently it seems that there is little evidence available to assist GPs in discriminating between patients complaining of palpitations who have significant cardiac arrhythmias and those who do not. OBJECTIVES: Our aim was to estimate discriminant functions for specific items of clinical information in relation to the categorization of a patient (aged over 18 years) with a symptom of new-onset palpitations presenting to primary care. METHODS: A network of 62 GPs spread amongst 36 practices agreed to recruit patients with new-onset palpitations over the course of a 9-month study period. Patients consenting to be involved in the study were asked a number of questions, focusing particularly on the medical history, and were requested to complete a Hospital Anxiety and Depression Scale. Each patient was also provided with a RhythmCard cardiac event recorder for up to 2 weeks and was asked to record their heart rhythm if they experienced palpitations. Odds ratios (adjusted for age and sex) were used to compare the clinical information obtained from patients with the final diagnosis. RESULTS: Of the 139 patients with palpitations presenting to GPs, it would appear that males [odds ratio = 2.1 (1.0-4.5)], those with regular palpitations [odds ratio = 2.5 (1.0-5.8)], those experiencing palpitations at work [odds ratio = 3.0 (1.3-7.2)] and those experiencing palpitations affected by sleeping (odds ratio = 3.3 (1.4-7.7)] were more likely to have a cardiac cause for their palpitations. Similar findings were made in an analysis focusing solely on the 81 patients with a RhythmCard result. Furthermore, amongst this group, it is interesting to note that patients with regular palpitations were more than twice as likely to have a 'significant' cardiac arrhythmia as a cause for their palpitations. There were suggestions of dose-response effects between the rate of the palpitation, the duration of the palpitation and the likelihood of it being a 'significant' arrhythmia. CONCLUSIONS: This study provides some information on the characteristics of patients reporting palpitations to GPs who may have 'significant' cardiac arrhythmias. Based on this work, we believe that a larger community-based study would be worthwhile and would provide useful and useable clinical discriminant information for GPs in the settings where they work and amongst the types of patients they encounter.

Adult↗

Effects of antecedent prolonged exercise on subsequent counterregulatory responses to hypoglycemia.

In the present study the hypothesis tested was that prior exercise may blunt counterregulatory responses to subsequent hypoglycemia. Healthy subjects [15 females (f)/15 males (m), age 27 +/- 1 yr, body mass index 22 +/- 1 kg/m(2), hemoglobin A(Ic) 5.6 +/- 0.5%] were studied during 2-day experiments. Day 1 involved either 90-min morning and afternoon cycle exercise at 50% maximal O2 uptake (VO2(max)) (priorEXE, n = 16, 8 m/8 f) or equivalent rest periods (priorREST, n = 14, 7 m/7 f). Day 2 consisted of a 2-h hypoglycemic clamp in all subjects. Endogenous glucose production (EGP) was measured using [3-3H]glucose. Muscle sympathetic nerve activity (MSNA) was measured using microneurography. Day 2 insulin (87 +/- 6 microU/ml) and plasma glucose levels (54 +/- 2 mg/dl) were equivalent after priorEXE and priorREST. Significant blunting (P < 0.01) of day 2 norepinephrine (-30 +/- 4%), epinephrine (-37 +/- 6%), glucagon (-60 +/- 4%), growth hormone (-61 +/- 5%), pancreatic polypeptide (-47 +/- 4%), and MSNA (-90 +/- 8%) responses to hypoglycemia occurred after priorEXE vs. priorREST. EGP during day 2 hypoglycemia was also suppressed significantly (P < 0.01) after priorEXE compared with priorREST. In summary, two bouts of exercise (90 min at 50% VO2(max)) significantly reduced glucagon, catecholamines, growth hormone, pancreatic polypeptide, and EGP responses to subsequent hypoglycemia. We conclude that, in normal humans, antecedent prolonged moderate exercise blunts neuroendocrine and metabolic counterregulatory responses to subsequent hypoglycemia.

3-Hydroxybutyric Acid↗

Effect of morning exercise on counterregulatory responses to subsequent, afternoon exercise.

The aim of this study was to determine whether a bout of morning exercise (EXE(1)) can alter neuroendocrine and metabolic responses to subsequent afternoon exercise (EXE(2)) and whether these changes follow a gender-specific pattern. Sixteen healthy volunteers (8 men and 8 women, age 27 +/- 1 yr, body mass index 23 +/- 1 kg/m(2), maximal O(2) uptake 31 +/- 2 ml x kg(-1) x min(-1)) were studied after an overnight fast. EXE(1) and EXE(2) each consisted of 90 min of cycling on a stationary bike at 48 +/- 2% of maximal O(2) uptake separated by 3 h. To avoid the confounding effects of hypoglycemia and glycogen depletion, carbohydrate (1.5 g/kg body wt po) was given after EXE(1), and plasma glucose was maintained at euglycemia during both episodes of exercise by a modification of the glucose-clamp technique. Basal insulin levels (7 +/- 1 microU/ml) and exercise-induced insulin decreases (-3 microU/ml) were similar during EXE(1) and EXE(2). Plasma glucose was 5.2 +/- 0.1 and 5.2 +/- 0.1 mmol/l during EXE(1) and EXE(2), respectively. The glucose infusion rate needed to maintain euglycemia during the last 30 min of exercise was increased during EXE(2) compared with EXE(1) (32 +/- 4 vs. 7 +/- 2 micromol x kg(-1) x min(-1)). Although this increased need for exogenous glucose was similar in men and women, gender differences in counterregulatory responses were significant. Compared with EXE(1), epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and cortisol responses were blunted during EXE(2) in men, but neuroendocrine responses were preserved or increased in women. In summary, morning exercise significantly impaired the body's ability to maintain euglycemia during later exercise of similar intensity and duration. We conclude that antecedent exercise can significantly modify, in a gender-specific fashion, metabolic and neuroendocrine responses to subsequent exercise.

Adult↗

Synthesis of mesoporous silica monoliths with embedded nanoparticles.

Mesostructured silica-nanoparticle monolithic composites have been synthesized by dispersing prefabricated nanoparticles of gold or zeolite (silicalite) in ethanolic reaction mixtures containing SiCl4 and a Pluronic triblock copolymer template. Whereas silicalite nanoparticles were used directly, surface functionalization of the gold nanoparticles with either primed silicate ions or a discrete 3-5-nm-thick silica shell was required to increase the interfacial compatibility with the hydrophilic poly(ethylene oxide) blocks. Under these conditions, the resulting monoliths consisted of distributed nanoparticles within an ordered mesostructured silica matrix. Removal of the polymer template by calcination produced corresponding mesoporous silica-nanoparticle replicas. The combination of the structure and the porosity of the silica framework with the crystal chemical properties of the embedded nanoparticles suggests that such composites should be useful as multifunctional materials.

Chlorides↗

Pretransplant tumor antigen-specific immunization of allogeneic bone marrow transplant donors enhances graft-versus-tumor activity without exacerbation of graft-versus-host disease.

Allogeneic bone marrow transplantation (BMT) causes a beneficial graft-versus-tumor (GVT) immune response that is often associated with graft-versus-host disease (GVHD). There is substantial interest in developing therapeutic strategies that augment GVT without GVHD. We have demonstrated recently that immunization of BMT donors with cellular tumor vaccines leads to curative GVT but induces unacceptable GVHD because of the presence of recipient minor histocompatibility antigens (mHAgs) in whole-cell tumor vaccines. This study tested the hypothesis that immunization of BMT donors against a defined tumor-specific antigen with a vaccine not containing recipient mHAgs would help to separate the two responses by enhancing GVT activity without exacerbating GVHD, even when cellular vaccines were used after BMT. Recipient strain C57BL/6 fibrosarcoma cells engineered to express the well-characterized model tumor antigen, influenza nucleoprotein (NP), were used in these studies. C3H.SW donors were immunized against NP prior to BMT, and cytolytic T cells were transferred along with bone marrow into irradiated H-2-matched, mHAg-mismatched C57BL/6 recipients with established micrometastatic 205-NP tumors. Donor immunization led to a significant increase in GVT activity, as measured by reduction in tumor growth and enhanced survival. However, deaths in recipients of tumor antigen-specific immune BMT ultimately occurred because of the growth of antigen-loss variants; such tumor growth did not occur in animals receiving BMT from donors treated with whole-cell vaccines. Donor immunization did not lead to an exacerbation of GVHD, even when BMT recipients received additional immunization after BMT with a 205-NP "whole" tumor cell vaccine (which was shown to induce fatal GVHD when used for donor immunization). In conclusion, immunization of allogeneic BMT donors against a tumor-specific antigen significantly enhances GVT activity without an associated exacerbation of GVHD.

Animals↗

The Chemistry of Form.

The emergence of complex form in living and nonliving systems remains a deep question for scientists attempting to understand the origins and development of shape and structure. In recent years, biologists and physicists have made significant advances in explaining fundamental problems in fields such as morphogenesis and pattern formation. Chemists, on the other hand, are only just beginning to contemplate the possibility of preparing manmade materials with lifelike form. This review traces a route to the direct synthesis of inorganic structures with biomimetic form, beginning from an understanding of crystal morphology and biomineralization. The equilibrium form of crystals can be modified by surface-active additives but only within limits dictated by the symmetry of the unit cell. In contrast, biological minerals, such as shells, bones, and teeth, are distinguished by a complexity of form that bears little resemblance to the underlying order of their inorganic crystals. By understanding the constructional processes that give rise to the inorganic structures of life it should be possible to develop a chemistry of form in the laboratory. For example, complex small-scale inorganic architectures are produced at room temperature by undertaking precipitation reactions in self-assembled organic media, such as surfactant micelles, block copolymer aggregates and microemulsion droplets. Unusual inorganic forms emerge when these reaction fields are subjected to instability thresholds and synthesis and self-assembly can be coupled to produce materials with higher-order organization. Like their biological counterparts, these hard inorganic structures represent new forms of organized matter which originate from soft chemistry.

Journal Article↗

Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels.

The structure of the cytoplasmic assembly of voltage-dependent K+ channels was solved by x-ray crystallography at 2.1 angstrom resolution. The assembly includes the cytoplasmic (T1) domain of the integral membrane alpha subunit together with the oxidoreductase beta subunit in a fourfold symmetric T1(4)beta4 complex. An electrophysiological assay showed that this complex is oriented with four T1 domains facing the transmembrane pore and four beta subunits facing the cytoplasm. The transmembrane pore communicates with the cytoplasm through lateral, negatively charged openings above the T1(4)beta4 complex. The inactivation peptides of voltage-dependent K(+) channels reach their site of action by entering these openings.

Animals↗

[Carotid endarterectomy and carotid stenting. A pilot study of a prospective, randomized and controlled comparison].

INTRODUCTION: A prospective, randomized and controlled trial is conducted to compare carotid endarterectomy and carotid stenting in high grade symptomatic carotid artery stenoses. METHODS: According to the study design symptomatic patients with a angiographically high-grade (> or = 70%) internal carotid artery stenosis are included. Pre- and postinterventional diagnostics during the hospitalization period includes neurological assessment, duplex sonography of the cervical and cerebral arteries and magnetic resonance imaging of the brain. Follow-up examinations are scheduled after 1, 6 and 12 months and consist of a neurological assessment and duplex sonography. After 12 months selective angiography and magnetic resonance imaging of the brain will be performed additionally. During a period of 9 months up to now 23/137 patients treated for a carotid artery stenosis were included in the study, 11 patients underwent surgery and 12 patients carotid stenting. RESULTS: Carotid stenting and endarterectomy was primarily successful without residual stenosis > 30% in each patient without the occurrence of stroke or death. In 18 follow-up examinations (neurological assessment including duplex sonography) of 13 patients (13 follow-up examinations after 30 days, 5 after 6 months) no relevant restenosis and no stroke occurred. CONCLUSION: As of yet, carotid stenting was a safe procedure. Due to the small number of patients a definitive conclusion can not be drawn.

Angiography, Digital Subtraction↗

Plasmapheresis combined with continuous venovenous hemofiltration in surgical patients with sepsis.

OBJECTIVE: To examine the effect of continuous venovenous hemofiltration (CVVHF) combined with plasmapheresis (TPE) in critically ill surgical patients after treatment of the septic focus. DESIGN: Observational pilot study. SETTING: University teaching hospital intensive care unit. INTERVENTIONS: TPE and CVVHF were administered 24 h after surgical and/or interventional treatment of septic focus. Arterial blood pressure, cardiac output, and systemic vascular resistance values were monitored. We examined the effect of the combined extracorporeal detoxification on outcome related to age, morbidity, organic failure rate, and initial APACHE II score. MEASUREMENTS AND RESULTS: Forty-three patients with sepsis were treated; 19 received TPE in combination with CVVHF, and 24 did not receive extracorporeal therapy. Overall mortality was 44.2%. In the therapy group mortality was lower (42.1 vs. 45.8%), but the primary organic failure rate was higher. The relationship between mortality and age was similar in the two groups. There was also no difference between the groups in the course of scores on APACHE II, multiple-organ failure, and sepsis severity. Only patients with an initial APACHE II score of 21-25 had a significant reduction in mortality after combined extracorporeal detoxification. Mortality of 17% in TPE/CVVHF patients with single- (pulmonary) and double-organ failure (renal/pulmonary) was significantly lower (P < 0.0001) than in untreated patients. CONCLUSIONS: Reduction in mortality in single- and double-organ failure was as high as 28% in septic patients with combined extracorporeal detoxification. A prospective randomized trial in sepsis and double-organ failure should be projected.

APACHE↗

Motion determination in actin filament fluorescence images with a spatio-temporal orientation analysis method.

We present a novel approach of automatically measuring motion in series of microscopic fluorescence images. As a differential method, the three-dimensional structure tensor technique is used to calculate the displacement vector field for every image of the sequence, from which the velocities are subsequently derived. We have used this method for the analysis of the movement of single actin filaments in the in vitro motility assay, where fluorescently labeled actin filaments move over a myosin decorated surface. With its fast implementation and subpixel accuracy, this approach is, in general, very valuable for analyzing dynamic processes by image sequence analysis.

Actins↗

Bridging the gap. Community partnerships in nursing education: advancing primary health care in practice.

An innovative approach to nursing education was piloted by the School of Nursing at Flinders University and Noarlunga Health Services, a generic community health service, in Adelaide, South Australia. The approach, encapsulated in the four-year Community Enrichment Project (CEP), focused on Primary Health Care (PHC) and nursing practice. The CEP developed curriculum and organised student placements, which promoted understanding of PHC in a way that integrated acute and community sectors. This paper considers the impact of splitting the students' third year final practicum, of seven weeks, between acute and community placements. Integral to the overall outcome of the project was the community agencies' cooperation in accepting students for longer clinical placements than had previously been the norm. This resulted in students being engaged in activities and projects in diverse areas. The students were aided in linking PHC theory to practice by the CEP team members who mentored them throughout these placements. Outcomes demonstrated the ability of students to integrate PHC theory to practice, across a variety of health settings. Students moved from a position of little knowledge or understanding of PHC, to an integrated knowledge of PHC principles and the relationship to enhanced nursing practice.

Attitude of Health Personnel↗