Search PubMed⌕ Search

Biomedical subjects

M Land

Publications and source records attributed to M Land.

At least 19 recordsLinked to original sources

The genome of the obligately intracellular bacterium Ehrlichia canis reveals themes of complex membrane structure and immune evasion strategies.

Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, alpha-proteobacterium, is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, 17 putative pseudogenes, and a substantial proportion of noncoding sequence (27%). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences and a unique serine-threonine bias associated with the potential for O glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly(G-C) tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Genes associated with pathogen-host interactions were identified, including a small group encoding proteins (n = 12) with tandem repeats and another group encoding proteins with eukaryote-like ankyrin domains (n = 7).

Animals↗

CD10 and Bcl-2 expression combined with the International Prognostic Index can identify subgroups of patients with diffuse large-cell lymphoma with very good or very poor prognoses.

AIMS: Diffuse large B-cell lymphoma (DLBCL) is characterized by marked biological heterogeneity. The identification of reproducible parameters that can be combined with the International Prognostic Index (IPI) to better predict outcome could lead to the development of effective risk-adaptive strategies. METHODS AND RESULTS: Bcl-2 and CD10 expression was determined by immunohistochemistry. The impact of the positivity on survival was evaluated in combination with the IPI in 86 patients with a confirmed diagnosis of DLBCL. Patients were divided according to the IPI into low-risk (no to two factors) or high-risk (three to five factors) groups. Positivity rates were 25% for CD10 and 42% for Bcl-2. In a Cox analysis, the high-risk IPI group [hazard ratio (HR) 5.98, P < 0.0001) and Bcl-2 expression (HR 2.43, P = 0.02) were independent poor prognostic factors, and expression of CD10 (HR 0.41, P = 0.052) predicted a favourable outcome. Among patients in the low-risk IPI group, CD10 positivity was associated with an excellent 8-year overall survival (92% versus 45%, P = 0.06). In the high-risk IPI group, Bcl-2 positivity identified a subgroup with invariably fatal disease. CONCLUSIONS: The expression of CD10 in the low-risk IPI group, and the expression of Bcl-2 in the high-risk IPI group can identify two subgroups of patients who might benefit from new risk-adaptive treatment approaches.

Adult↗

Rate of perioperative complications in thermal ablation of bone: an animal trial.

INTRODUCTION: While only few data are available yet for radioablation of bone tissue, the occurrence of bone marrow embolisms during cryoablation has been documented. It was the aim of this study to assess perioperative complication rates of thermoablation in animals using state-of-the-art ablation probes. MATERIALS AND METHODS: Eight adult sheep were placed under general anaesthesia, and using a radioprobe, thermoablation was performed on the medial side of the head of the right tibia. In addition, freezing was performed with miniature cryoprobes on both femurs and the head of the left tibia. Haemodynamic monitoring and determination of blood gases and electrolytes were done intraoperatively. The animals were killed 1 week after surgery, and the ablation sites and lung tissue examined macroscopically and microscopically. RESULTS: None of the animals showed pathological changes in any of these parameters. Blood gases remained unremarkable throughout the operation. All eight animals showed an average drop in haemoglobin of 0.97 g/100 ml. Two animals showed fresh embolisms in the pulmonary vessels. CONCLUSION: Experimental thermoablation of bone tissue in large animals failed to show any significant perioperative complications following surgery. The lung embolisms which did occur were not clinically relevant. The use of mini-cryoprobes or radioprobes as alternative or complementary measures for treating pathologically altered bone tissue seems viable and does not involve any undue risks.

Animals↗

The genome of a motile marine Synechococcus.

Marine unicellular cyanobacteria are responsible for an estimated 20-40% of chlorophyll biomass and carbon fixation in the oceans. Here we have sequenced and analysed the 2.4-megabase genome of Synechococcus sp. strain WH8102, revealing some of the ways that these organisms have adapted to their largely oligotrophic environment. WH8102 uses organic nitrogen and phosphorus sources and more sodium-dependent transporters than a model freshwater cyanobacterium. Furthermore, it seems to have adopted strategies for conserving limited iron stores by using nickel and cobalt in some enzymes, has reduced its regulatory machinery (consistent with the fact that the open ocean constitutes a far more constant and buffered environment than fresh water), and has evolved a unique type of swimming motility. The genome of WH8102 seems to have been greatly influenced by horizontal gene transfer, partially through phages. The genetic material contributed by horizontal gene transfer includes genes involved in the modification of the cell surface and in swimming motility. On the basis of its genome, WH8102 is more of a generalist than two related marine cyanobacteria.

Bacterial Proteins↗

Cryosurgery in long bones with new miniature cryoprobe: an experimental in vivo study of the cryosurgical temperature field in sheep.

AIM: The aim of this in vivo study was to determine whether new miniature cryoprobes provide adequate tissue cooling in long bones by measuring the field of temperature under various conditions. METHODS: Freezings were performed in femoral and tibial bones of 10 sheep under general anaesthesia. Applying one cryoprobe, temperatures of -75 degrees C resp. -51 degrees C could be reached within 0.75 cm resp. 1.00 cm of the probe. RESULTS: Histological examinations revealed compact bone and marrow necroses along the isotherm in all 10 sheep. Using two cryoprobes simultaneously, a mean temperature decrease to -71 degrees C between the two cryoprobes was achieved thanks to the synergistic freezing effect. Looking at consecutive freezes, it was apparent that with similar cryoprobe end temperatures, the temperature dropped faster if the number of freezing cycles was increased. CONCLUSION: In conclusion, it was seen that despite its small diameter, the new miniature cryoprobe delivers adequate in vivo tissue cooling in long tubular bones. Employing the synergistic freezing effect by using two or more cryoprobes simultaneously, efficient in vivo freezing of larger bone segments is also possible. Thus, cryosurgery with the new miniature probes can provide a valuable complement to conventional resection of long tubular bones, and offers a viable alternative to surgical treatment of neoplastic diseases of the skeletal system.

Animals↗

The cryosurgical ablation of bone tissue by means of a new miniature cryoprobe -- evaluation of the probe and adaption of the method to in vitro human bone.

Until now, modern miniature cryoprobes have been used successfully for the local destruction of soft-tissue tumors without damaging adjacent healthy tissue. In this study, the methodology of cryoablation was applied to bone, and the freezing effect as well as the cooling capacity of the probe were examined. Freezing was performed by cooling one or two probes, with a diameter of 3.2 mm, to -180 degrees C with liquid nitrogen. The cooling capacity of the probes was determined under optic and thermic control in a homogenous reference gel (gelatin), followed by an in vitro measurement on human bone. The simultaneous use of 2 probes resulted in a synergistic effect which produced an almost spherical expansion of frozen area in the homogenous gelatin. In vitro freezing of human tibiae produced equivalent freezing temperatures, with one or two probes, in comparison to the homogenous gelatin. An adequate tissue cooling of bone matrix can be achieved through the use of one or more miniature cryoprobes so that after in vivo testing, the use of this probe could possibly become an alternative or supplement to the surgical resection of pathologic bone processes.

Bone Matrix↗

Human chromosome 19 and related regions in mouse: conservative and lineage-specific evolution.

To illuminate the function and evolutionary history of both genomes, we sequenced mouse DNA related to human chromosome 19. Comparative sequence alignments yielded confirmatory evidence for hypothetical genes and identified exons, regulatory elements, and candidate genes that were missed by other predictive methods. Chromosome-wide comparisons revealed a difference between single-copy HSA19 genes, which are overwhelmingly conserved in mouse, and genes residing in tandem familial clusters, which differ extensively in number, coding capacity, and organization between the two species. Finally, we sequenced breakpoints of all 15 evolutionary rearrangements, providing a view of the forces that drive chromosome evolution in mammals.

Animals↗

Another look at seasonal variation in patch test results. A multifactorial analysis of surveillance data of the IVDK. Information Network of Departments of Dermatology.

There is conflicting evidence concerning seasonal variability of patch test results and no evidence concerning the influence of season on weak-positive, possibly false-positive, irritant reactions, which was analysed in the present study. Data collected in the German Information Network of Departments of Dermatology (IVDK) 1992 to 1997 were combined with external environmental data on temperature and absolute humidity in Germany, and bivariate as well as logistic regression analyses performed concerning the association between reactivity to selected allergens and air temperature and absolute humidity on the respective days of patch testing. Between 39,239 and 41,629 patients had been tested with the 4 allergens considered here. Only formaldehyde exhibited a distinct increase in questionable or irritant as well as weak-positive reactions associated with dry, cold weather. Methylchloroisothiazolinone/methylisothiazolinone and lanolin alcohol showed only a weak, and epoxy resin no, association with climatic conditions. The results indicate that weak-positive reactions, at least to formaldehyde as a prototype of an allergen which is at the same time a marginal irritant, may sometimes be irritant rather than allergic. Patients showing these should be re-tested to improve the poor reproducibilty observed with this allergen.

Climate↗

Native tissue second harmonic imaging improves endocardial and epicardial border definition in dobutamine stress echocardiography.

AIMS: Native tissue second harmonic imaging (SHI) implemented in two-dimensional (2D) echocardiography was found to improve left ventricular (LV) endocardial border delineation. Dobutamine stress echocardiography (DSE) depends on the ability to adequately visualize these borders. We analysed whether SHI, compared to fundamental imaging (FI), can improve echogenicity qualitatively and quantitatively, as well as looking at the diagnostic accuracy of the stress test. METHODS AND RESULTS: Fifty consecutive patients with suspected or known coronary artery disease (history of myocardial infarction and/or coronary artery bypass grafting) underwent DSE sequentially by SHI as well as FI 3 days before or after quantitative coronary angiography. Regional mean echogenicity scores (0=uninterpretable; 4=excellent imaging) for SHI and FI at peak dobutamine titration were 1.8 +/- 0.8 and 1.0 +/- 0.6 (P=0.0020) for the anterior region, 2.3 +/- 0.8 and 1.5 +/- 0.7 (P=0.0002) laterally, 2.7 +/- 1.0 and 1.9 +/- 0.8 (P=0.0001) posteriorly, 2.9 +/- 0.8 and 2.2 +/- 0.7 (P<0.0006) inferiorly, 3.0 +/-0.7 and 2.2 +/- 0.7 (P=0.0001) septally, and 3.1 +/- 1.0 and 2.1 +/-0.8 (P=0.0001) anteroseptally, respectively. Medians [upper; lower quartiles] of a global endocardial visualization index (calculated analogously with the wall motion score index based on a 16-segment model recommended by the American Society of Echocardiography) for the harmonic and the fundamental techniques were 2.59 [2.91; 2.22] and 1.87 [2.19; 1.53] (P=0.0001) at rest, 2.62 [2.94; 2.13] and 1.84 [2.19; 1.50] (P=0.0001) at low dose dobutamine, 2.51 [3.00; 2.13] and 1.74 [2.00; 1.44] (P=0.0001) at peak dose dobutamine, and 2.52 [2.94; 2.19] and 1.76 [2.19; 1.38] (P=0.0001) at recovery, respectively. For repeated quantitative LV volumetry in the harmonic and fundamental modality by the same observer, coefficients of variation were 4.4 +/- 0.4 vs. 6.0 +/- 0.5 (P<0.0001) for end-diastolic volume, 7.4 +/- 0.8 vs. 9.2 +/- 1.1 (P<0.0001) for end-systolic volume, and 5.2 +/- 1.1 vs. 8.2 +/- 1.3 (P<0.0001) for ejection fraction, respectively. Sensitivity and specificity related to coronary angiography for both methods were 80% and 60% as well as 90% and 93%, respectively. CONCLUSION: Native tissue SHI enhances LV image quality in all stress stages of DSE in unselected patients. This translates into beneficial effects on not only qualitative but also quantitative testing and diagnostic accuracy. SHI should be recommended as a standard tool in DSE and extends its applicability to difficult-to-image patients previously deemed unsuitable.

Adult↗

Partitioning methods for multifactorial risk attribution.

The epidemiological problem of risk attribution in the framework of multiple exposures has been the subject of intensive research activities in the last decade. In particular, partitioning methods have been developed to define new multidimensional measures of attributable risk putting the task of quantifying a proportion of disease events in a population that can be ascribed to the adverse health effects of certain risk factors into a multifactorial perspective. The parameters generalize the concept of attributable risk to different multifactorial frameworks in which multiple exposures might be arranged in hierarchically ordered classes or in equally ranking groups. Partitioning methods are reviewed and differences between the multifactorial variants of attributable risk are illustrated by a component causes model.

Algorithms↗

Functional impairment and cognition in bipolar disorder.

Bipolar disorder is a common, chronic and severe mental disorder, affecting approximately 2% of the adult population. Bipolar disorder causes substantial psychosocial morbidity that frequently affects the patient's marriage, children, occupation, and other aspects of the patient's life. Few studies have examined the functional impairment in patients with affective illness. Earlier outcome studies of mania reported favorable long-term outcomes. However, modern outcome studies have found that a majority of bipolar patients evidence high rates of functional impairment. These low reports of functional recovery rates are particularly surprising. The basis for such limited functional recovery is not entirely clear. Factors associated with functional dysfunction include presence of inter-episode symptoms, neuroleptic treatment, lower social economic class, and lower premorbid function. Cognitive dysfunction, a symptom domain of schizophrenia, has been identified as an important measure of outcome in the treatment of schizophrenia. Recently, there has been some suggestion that there may be impaired neuropsychological performance in euthymic patients with recurring mood disorders. Whether impaired neuropsychological performance in associated with the functional impairment in bipolar patients who have achieved syndromal recovery is an intriguing question. The literature on functional impairment and cognition in bipolar disorder is reviewed.

Adult↗

Pertussis antibody levels in infants immunized with an acellular pertussis component vaccine, measured using whole-cell pertussis ELISA.

A commercially available whole-cell pertussis IgG ELISA was used to test the response of 137 2-month-old infants to immunization with a trivalent acellular pertussis vaccine. The pre-immunization geometric mean (GM) IgG index was 6.96 (95% confidence interval (CI) 5.88-8.04) and the postimmunization GM index was 13.16 (95% CI 12. 20-14.11), P < 0.001. Eighty percent of subjects (110/137) had a significant 1.5-fold increase of pertussis IgG index (97/137, 71%) or a postimmunization IgG index > 10 (93/137, 68%). In single antigen ELISA, 83% showed at least a fourfold increase in pertussis toxin-specific IgG (PT-IgG) and 91% showed an increase in IgG specific for filamentous haemagglutinin (FHA-IgG). Four percent had high pre- immunization antibody levels (index > 20), likely to reflect recent maternal exposure to pertussis. This correlated with a smaller increase in pertussis IgG index. A decline in pertussis IgG index postimmunization occurred in 17/24 infants (71%) whose pre-immunization IgG index was > 10. This postimmunization pertussis IgG index was not significantly different to that of infants with a low pre-immunization index. A similar trend was noted with PT-IgG and FHA-IgG results. The whole-cell ELISA can detect a response to acellular pertussis vaccination in most infants if both antibody index and degree of seroconversion are calculated and at least one criterion is satisfied.

Antibodies, Bacterial↗

Surfactant treatment of neonates with respiratory failure and group B streptococcal infection. Members of the Collaborative European Multicenter Study Group.

OBJECTIVE: Connatal pneumonia caused by group B streptococcal (GBS) infection may be associated with surfactant dysfunction. We investigated the effects of surfactant treatment in term and preterm neonates with GBS infection and respiratory failure, in comparison with corresponding data from a control population of noninfected infants treated with surfactant for respiratory distress syndrome (RDS). DESIGN/METHODS: The study comprised 118 infants with respiratory failure, clinical and/or laboratory signs of acute inflammatory disease, and GBS infection proven by culture results. They were recruited retrospectively from a database of patients treated with surfactant at 28 neonatology units participating in European multicenter trials (1987-1993) and prospectively from the same units in the following years. A nonrandomized control group of 236 noninfected infants was selected from the same database. The primary parameters evaluated were oxygen requirement, ventilator settings, and incidence of complications. RESULTS: Median birth weight in the GBS study group was 1468 g (25th-75th percentiles: 1015-2170), and median gestational age was 30 (27-33) weeks. Thirty-one percent of the infants weighed >2000 g. Median age at surfactant treatment was 6 hours. The mean initial surfactant dose was 142 mg/kg (standard deviation: 53). Ninety of the infants were treated with Curosurf (Chiesi Farmaceutici, Parma, Italy), 13 with Survanta (Abboth GmbH, Wiesbaden, Germany), 12 with Alveofact (Dr Karl Thomae GmbH, Biberach, Germany), and 3 with Exosurf (Wellcome GmbH, Burgwedel, Germany). Within 1 hour of surfactant treatment, median fraction of inspiratory oxygen was reduced from .84 (25th-75th percentiles:.63-1.0) to.50 (.35-.80). The incidence of complications in the study group (mortality: 30%; pneumothorax: 16%; intracranial hemorrhage: 42%) was high, compared with infants with RDS. CONCLUSIONS: Surfactant therapy improves gas exchange in the majority of patients with GBS pneumonia. The response to surfactant is slower than in infants with RDS, and repeated surfactant doses are often needed. The mortality and morbidity are substantial, considering the relatively high mean birth weight of the treated infants.

Drug Administration Schedule↗

Behavioural evidence for polarisation vision in stomatopods reveals a potential channel for communication.

Polarisation sensitivity (PS) - the ability to detect the orientation of polarised light - occurs in a wide variety of invertebrates [1] [2] and vertebrates [3] [4] [5], many of which are marine species [1]. Of these, the crustacea are particularly well documented in terms of their structural [6] and neural [7] [8] adaptations for PS. The few behavioural studies conducted on crustaceans demonstrate orientation to, or local navigation with, polarised sky patterns [9]. Aside from this, the function of PS in crustaceans, and indeed in most animals, remains obscure. Where PS can be shown to allow perception of polarised light as a 'special sensory quality' [1], separate from intensity or colour, it has been termed polarisation vision (PV). Here, within the remarkable visual system of the stomatopod crustaceans (mantis shrimps) [10], we provide the first demonstration of PV in the crustacea and the first convincing evidence for learning the orientation of polarised light in any animal. Using new polarimetric [11] and photographic methods to examine stomatopods, we found striking patterns of polarisation on their antennae and telson, suggesting that one function of PV in stomatopods may be communication [12]. PV may also be used for tasks such as navigation [5] [9] [13], location of reflective water surfaces [14] and contrast enhancement [1] [15] [16] [17] [18]. It is possible that the stomatopod PV system also contributes to some of these functions.

Animals↗

The roles of vision and eye movements in the control of activities of daily living.

The aim of this study was to determine the pattern of fixations during the performance of a well-learned task in a natural setting (making tea), and to classify the types of monitoring action that the eyes perform. We used a head-mounted eye-movement video camera, which provided a continuous view of the scene ahead, with a dot indicating foveal direction with an accuracy of about 1 deg. A second video camera recorded the subject's activities from across the room. The videos were linked and analysed frame by frame. Foveal direction was always close to the object being manipulated, and very few fixations were irrelevant to the task. The first object-related fixation typically led the first indication of manipulation by 0.56 s, and vision moved to the next object about 0.61 s before manipulation of the previous object was complete. Each object-related act that did not involve a waiting period lasted an average of 3.3 s and involved about 7 fixations. Roughly a third of all fixations on objects could be definitely identified with one of four monitoring functions: locating objects used later in the process, directing the hand or object in the hand to a new location, guiding the approach of one object to another (e.g. kettle and lid), and checking the state of some variable (e.g. water level). We conclude that although the actions of tea-making are 'automated' and proceed with little conscious involvement, the eyes closely monitor every step of the process. This type of unconscious attention must be a common phenomenon in everyday life.

Activities of Daily Living↗

Averaging attributable fractions in the multifactorial situation: assumptions and interpretation.

In multifactorial situations, the concept of attributable fraction quantifying the population impact of exposure factors on the disease load needs special methodologic care to take the interrelationship between exposures into account. Recently, new epidemiologic parameters have been introduced to address this issue. These approaches are reconsidered here from a game-theoretical perspective. The derivation of game-theoretical properties of these parameters provides additional motivation for their use in epidemiologic practice and offers new insights into their interpretation in epidemiologic studies. The nontechnical description of the results is illustrated by examples from the Hordaland study on obstructive lung disease.

Causality↗