Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers syndrome gene in left-sided colon cancer

We analyzed somatic mutation and loss of heterozygosity (LOH) in the serine/threonine kinase 11 (STK11)/Peutz-Jeghers syndrome gene in 49 colorectal tumors in three different stages of a dysplasia-carcinoma sequence. We detected LOH in 10 of 19 (52.6%) informative colorectal cancers at loci D19S886 and/or D19S883, but no LOH was observed in 25 informative adenomas. We detected a total of 9 somatic mutations [7 of 13 (53.8%) left-sided colon cancers and 2 of 7 (28.6%) left-sided adenomas with high-grade dysplasia], but no mutations were detected in right-sided colon tumors. Of the nine mutations, one was a frameshift mutation (the same mutation detected in Peutz-Jeghers syndrome family previously), and the other eight were missense mutations. This results indicate that STK11 is a tumor suppressor gene and that genetic changes of STK11 play an important role in left-sided colon cancer carcinogenesis.     

Gene-pool variation in caledonian and European Scots pine (Pinus sylvestris L.) revealed by chloroplast simple-sequence repeats

We have used polymorphic chloroplast simple-sequence repeats to analyse levels of genetic variation within and between seven native Scottish and eight mainland European populations of Scots pine (Pinus sylvestris L.). Diversity levels for the Scottish populations based on haplotype frequency were far in excess of those previously obtained using monoterpenes and isozymes and confirmed lower levels of genetic variation within the derelict population at Glen Falloch. The diversity levels were higher than those reported in similar studies in other Pinus species. An analysis of molecular variance (AMOVA) showed that small (3.24-8.81%) but significant (p < or = 0.001) portions of the variation existed between the populations and that there was no significant difference between the Scottish and the mainland European populations. Evidence of population substructure was found in the Rannoch population, which exhibited two subgroups. Finally, one of the loci studied exhibited an allele distribution uncharacteristic of the stepwise mutation model of evolution of simple-sequence repeats, and sequencing of the PCR products revealed that this was due to a duplication rather than slippage in the repeat region. An examination of the distribution of this mutation suggests that it may have occurred fairly recently in the Wester Ross region or that it may be evidence of a refugial population.     

A structural basis for memory storage in mammals

It is proposed that altered dendrite length and de novo formation of new dendrite branches in cholinoceptive cells are responsible for long-term memory storage, a process enabled by the degradation of microtubule-associated protein-2. These memories are encoded as modality-specific associable representations. Accordingly, associable representations are confined to cytoarchitectonic modules of the cerebral cortex, hippocampus, and amygdala. The proposed sequence of events leading to long-term storage in cholinoceptive dendrites begins with changes in neuronal activity, then in neurotrophin release, followed by enhanced acetylcholine release, muscarinic response, calcium influx, degradation of microtubule-associated protein-2, and finally new dendrite structure. Hypothetically, each associable representation consists of altered dendrite segments from approximately 5000-15,000 cholinoceptive cells contained within one or a few module(s). Simultaneous restructuring during consolidation of long-term memory is hypothesized to result in a similar infrastructure among dendrite sets, facilitating co-activation of those dendrite sets by neurotransmitters such as acetylcholine, and conceivably enabling high energy interactions between those dendrites by phenomena such as quantum optical coherence. Based on the specific architecture proposed, it is estimated that the human telecephalon contains enough dendrites to encode 50 million associable representations in a lifetime, or put another way, to encode one new associable representation each minute. The implications that this proposal has regarding treatments for Alzheimer's disease are also discussed.     

Post transfusion non-cardiogenic pulmonary edema in a patient with chemotherapy-related hemolytic uremic syndrome

Recent experimental studies performed at the Dept of Orthopaedics at Gothenburg University have systematically assessed the basic pathophysiological mechanisms behind sciatica due to disc herniation. It has hereby been seen that the epidural presence of nucleus pulposus may induce structural and functional injury of the adjacent nerve roots similar in magnitude to those induced by mechanical deformation. By increasing the knowledge of the substances and mechanisms leading to this nucleus pulposus-induced nerve injury it may be assumed that sciatica to a certain extent may be treated by specific pharmacologic agents in the future, in combination with existing treatment modalities.     

Reopening of macular holes after initially successful repair

OBJECTIVE: To evaluate the frequency and prognosis of reopening of a macular hole after initially successful repair in a defined patient cohort. DESIGN: Retrospective consecutive noncomparative case series. PARTICIPANTS: Seventeen cases of reopened macular holes among 390 cases of idiopathic macular holes that previously had undergone macular hole surgery were studied. MAIN OUTCOME MEASURES: Assessment of demographics, visual acuity, preoperatively, postoperatively, after reopening of macular hole and after reoperation, if applicable, and precipitating factors. RESULTS: There were 17 (4.8%) of 353 cases in which the macular hole reopened after initial successful surgical closure. The mean visual acuity before reopening was 20/48 and was 20/133 after reopening. Twelve eyes underwent reoperation with improvement to a mean visual acuity of 20/54. The five eyes that were not reoperated on maintained a mean visual acuity of 20/200. Ten of the eyes had undergone cataract surgery between macular hole surgeries, but in only one did the reopening appear to occur in association with this procedure. CONCLUSIONS: Reopening of a previously successfully operated macular hole is uncommon and seems to be a spontaneous event. Reoperation generally yields results similar to those present before the reopening. Reopening of a macular hole associated with cataract surgery is rare.     

Reprioritization of liver protein synthesis resulting from recombinant human growth hormone supplementation in parenterally fed trauma patients: the effect of growth hormone on the acute-phase response

BACKGROUND: One of the major components of the metabolic response to severe trauma is the alteration in concentrations of a large number of plasma proteins referred to as acute-phase proteins (APP). The principle mediators of these liver-synthesized APP are mainly the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). METHODS: We have measured the plasma levels of IL-6, TNF alpha, and 20 APP in 24 adult, severely injured, hypermetabolic and highly catabolic patients with multiple injuries within 48-60 hours after injury, when they were receiving maintenance fluids without calories or nitrogen, and subsequently during 7 days of total parenteral nutrition with (n = 12) or without (n = 12) recombinant human growth hormone supplementation (rhGH, 0.15 mg/kg/d). RESULTS: Baseline positive APP due to severe trauma include C-reactive protein (CRP), alpha-1 antichymotrypsin, alpha-1 acid glycoprotein, alpha-1 antitrypsin, fibronectin, and factor B. Negative APP include IgG, IgM, complement-3, prealbumin, transferrin, ceruloplasmin, and albumin. Except for CRP, alpha-1 antichymotrypsin, and albumin, all the APP levels increase during 7 days of nutritional support. Plasma levels of cytokines IL-6 and TNF-alpha, although initially markedly increased after injury, decrease with parenteral refeeding. There is a linear correlation between CRP and IL-6 levels and also between the transport proteins prealbumin and transferrin. Trauma-induced increases in CRP and IL-6 levels decreased with nutrition alone, but did not change with rhGH supplementation. An immunosuppressed state of injury is evident from the decreased immunoglobulin levels (IgG, IgM, IgA) in the trauma patients. Total parenteral nutrition alone increases the immunoglobulin levels to normal. However, with adjuvant rhGH, only IgA levels are normalized. CONCLUSIONS: Adjuvant rhGH therapy does not attenuate the reprioritization of acute liver protein synthesis and results in only limited restoration of host defenses. The clinical implications of these findings await further study.     

Method for segmenting chest CT image data using an anatomical model: preliminary results

We present an automated, knowledge-based method for segmenting chest computed tomography (CT) datasets. Anatomical knowledge including expected volume, shape, relative position, and X-ray attenuation of organs provides feature constraints that guide the segmentation process. Knowledge is represented at a high level using an explicit anatomical model. The model is stored in a frame-based semantic network and anatomical variability is incorporated using fuzzy sets. A blackboard architecture permits the data representation and processing algorithms in the model domain to be independent of those in the image domain. Knowledge-constrained segmentation routines extract contiguous three-dimensional (3-D) sets of voxels, and their feature-space representations are posted on the blackboard. An inference engine uses fuzzy logic to match image to model objects based on the feature constraints. Strict separation of model and image domains allows for systematic extension of the knowledge base. In preliminary experiments, the method has been applied to a small number of thoracic CT datasets. Based on subjective visual assessment by experienced thoracic radiologists, basic anatomic structures such as the lungs, central tracheobronchial tree, chest wall, and mediastinum were successfully segmented. To demonstrate the extensibility of the system, knowledge was added to represent the more complex anatomy of lung lesions in contact with vessels or the chest wall. Visual inspection of these segmented lesions was also favorable. These preliminary results suggest that use of expert knowledge provides an increased level of automation compared with low-level segmentation techniques. Moreover, the knowledge-based approach may better discriminate between structures of similar attenuation and anatomic contiguity. Further validation is required.