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Seven years' experience with Integra as a reconstructive tool.

The bilayered dermal substitute Integra (Integra Life Sciences Corp., Plainsboro, NJ) was developed and has been widely used as primary coverage for excised acute burns. Our take has been slightly different, finding it most useful in the management of complex soft-tissue loss and threatened extremities as the result of tendon, joint, or bone exposure. Often tasked to fill significant volume loss, we have become adept at stacked multiple-layer applications. Creative use of this material has resulted in unexpected successes with distal limb salvage; the technique takes its place beside adjacent tissue transfer, composite flaps, and vascular pedicle flaps in our burn reconstructive practice. A prospective registry (44 patients) has been kept during the past 7 years that catalogs wounds with complex soft-tissue loss treated with Integra grafts. Many of these patients were at risk of extremity loss because of exposed tendons, joints, or bone. Integra was applied after 1:1 meshing. With profound soft-tissue defects, multiple layers of Integra were serially applied 1 to 2 weeks apart for reconstitution of soft-tissue contours. Local Integra graft infections were managed by silicone unroofing followed by topical sulfamylon liquid dressings. Wounds addressed included fourth-degree burns, necrotizing fasciitis, pit-viper envenomations, and total abdominal wall avulsion in one patient after being run over by a bus. Patients generally were free of pain from their wounds during the maturation phase of the Integra neodermis. Restoration of tissue contour was significantly better when using multiple layers for deep defects. Second and third layers of Integra were successfully applied after an abbreviated first graft maturation period of 7 days. Epithelial autografts on multilayer Integra applications frequently "ghosted"; they would auto-digest to dispersed cells followed subsequently by the reappearance of a confluent epithelial layer. Final grafted skin morphology over palmar and plantar surfaces assumed the type and fingerprint pattern of the original tissues. Infections were readily visible. Early recognition kept them to easily treated circumscribed areas, which did not jeopardize the entire wound. Lengths of stay were long (range, 2-246 days) but not significantly greater than with traditional techniques. The specific reconstructive use of Integra permitted unexpected salvage of several threatened extremities by protecting exposed tendons, bones and joints. Long-term histologic examination revealed unexpected persistence of Integra collagen. Large volume loss wounds benefited from the ability to fill voids with multilayered applications.

Abdominal Injuries↗

Modelling the thermal evolution of enzyme-created bubbles in DNA.

The formation of bubbles in nucleic acids (NAs) is fundamental in many biological processes such as DNA replication, recombination, telomere formation and nucleotide excision repair, as well as RNA transcription and splicing. These processes are carried out by assembled complexes with enzymes that separate selected regions of NAs. Within the frame of a nonlinear dynamics approach, we model the structure of the DNA duplex by a nonlinear network of coupled oscillators. We show that, in fact, from certain local structural distortions, there originate oscillating localized patterns, that is, radial and torsional breathers, which are associated with localized H-bond deformations, reminiscent of the replication bubble. We further study the temperature dependence of these oscillating bubbles. To this aim, the underlying nonlinear oscillator network of the DNA duplex is brought into contact with a heat bath using the Nosé-Hoover method. Special attention is paid to the stability of the oscillating bubbles under the imposed thermal perturbations. It is demonstrated that the radial and torsional breathers sustain the impact of thermal perturbations even at temperatures as high as room temperature. Generally, for non-zero temperature, the H-bond breathers move coherently along the double chain, whereas at T=0 standing radial and torsional breathers result.

DNA↗

Cryptic species of planktonic foraminifera: their effect on palaeoceanographic reconstructions.

Shells of planktonic foraminifera recovered from marine sediments provide a multitude of important palaeoproxies. Most of these proxies are based on the assumption that each morphospecies of planktonic foraminifera represents a genetically continuous species with a unique habitat. Recent discovery of hitherto hidden genetic diversity among modern planktonic foraminifera has significant repercussions on palaeoproxies derived from their fossil shells. We have compiled all available data on this genetic diversity. To date, 33 cryptic genetic types were found in 9 out of the 22 sequenced morphospecies of modern planktonic foraminifera. An examination of this database suggests that cryptic genetic diversity may be a prevalent pattern among modern planktonic foraminifera, but that the total number of cryptic genetic types per morphospecies is not large and that most genetic types show a non-random pattern of distribution in the oceans. Using modern distribution data from the Atlantic Ocean as constraints, the relationship between abundances of three genetic types of Globigerina bulloides and sea-surface temperature has been modelled and this model has been applied to a database of species counts in Atlantic coretops (761 samples). Trials with artificial neural networks (ANNs), the modern analogue technique and Imbrie-Kipp transfer functions showed that the splitting of G. bulloides into three genetic types resulted in substantial reduction in the prediction error rate (by 5 to 34%) and that this improvement was by far greatest in ANN trials (on average more than 20%). We conclude that such a large reduction in error rate occurred because the models resonated with a real pattern in the original data. This study indicates that genetic diversity among planktonic foraminifera may become more of a gift than malaise to palaeoproxies. If it becomes possible to distinguish these genetic types in the fossil record, the accuracy of proxies based on planktonic foraminifera will indeed substantially increase.

Animals↗

Dynamical ordering of driven stripe phases in quenched disorder.

We examine the dynamics and stripe formation in a system with competing short and long-range interactions in the presence of both an applied dc drive and quenched disorder. Without disorder, the system forms stripes organized in a labyrinth state. We find that, when the disorder strength exceeds a critical value, an applied dc drive can induce a dynamical stripe ordering transition to a state that is more ordered than the originating undriven, unpinned pattern. We show that signatures in the structure factor and transport properties correspond to this dynamical reordering transition, and we present the dynamic phase diagram as a function of strengths of disorder and dc drive.

Journal Article↗

Multivariate analysis of single-molecule spectra: surpassing spectral diffusion.

The full exploitation of single-molecule spectroscopy in disordered systems is often hampered by spectral diffusion processes of the optical transitions due to structural fluctuations in the local environment of the probe molecule which leads to temporal averaging of the signal. Multivariate statistical pattern recognition techniques, originally developed for single-molecule cryoelectron microscopy, allow us to retrieve detailed information from optical single-molecule spectra. As an example, we present the phonon side band of the B800 excitations of the light-harvesting 2 (LH2) complex from Rhodospirillum molischianum, revealing the electron-phonon coupling strength for these transitions. The measured Debye-Waller factors, ranging from 0.4 to 0.9, fall in the regime of weak electron-phonon coupling.

Journal Article↗

Superspace description of the structure of the composite crystal urea/n-octane at room temperature.

A structural model for the composite crystal urea/n-octane is proposed. Despite the lack of information from the largely disordered guest substructure, the final model is consistent with the collected diffraction pattern. The use of the superspace approach stresses the composite character of the inclusion compounds and makes easier a unified view of the whole urea/n-alkane family. In particular, a comparison between the octane and heptadecane derivatives shows a common pattern for the origin of the modulation of the guest chains based on the distribution of the NH(2) groups within each tunnel wall.

Journal Article↗

Malignant lymphoma in coeliac disease: various manifestations with distinct symptomatology and prognosis?

OBJECTIVES: To study the different forms of malignant lymphoma complicating coeliac disease in a low-prevalence area, according to extranodal-nodal and extraintestinal-intestinal manifestations. SUBJECTS AND SETTING: Patients recruited from two University Hospitals (Amsterdam, Leiden) and from PALGA (National Dutch data-bank) over a 16-year period. DESIGN: Review of hospital charts with respect to clinical presentation and treatment of both coeliac disease and malignant lymphoma. Re-evaluation of morphology and staging by immunoperoxidase, enzyme- and immunohistochemical stainings on unstained and frozen materials. MAIN OUTCOME MEASURES: Clinical behaviour and T- or B-cell morphology of extranodal intestinal, extranodal extraintestinal and nodal intestinal disease. RESULTS: Fourteen cases of enteropathy-associated lymphoma could be traced, 10 with a history of coeliac disease, four primarily presenting with malignant lymphoma. The usual extranodal intestinal lymphoma (eight cases) presented with abdominal pain, weight loss, and malabsorption. Six had atypical disease: four presented with extranodal extraintestinal disease, located in the skin or the respiratory tract; two patients had intractable malabsorption and oedema caused by a nodal intestinal lymphoma. Re-evaluation with additional immunohistochemical stainings in 11 patients showed a pleomorphic malignant infiltrate of histiocyte-like cells of T-cell origin, with a pattern of CD3+; CD4-; CD5 +/-; CD7+ and CD8-. It also established a more appropriate diagnosis in four, an 0.6-year earlier diagnosis in six, and an upgraded stage of disease in two patients. A more extensive spread and poorer outcome appeared to become more probable in the ranking order of extranodal intestinal, extranodal extraintestinal and nodal intestinal lymphoma. CONCLUSIONS: A proper and timely diagnosis of enteropathy-associated lymphoma requires clinical vigilance and unrelentless perseverance to obtain adequate fresh and frozen tissue for histochemical staining. Further research in a larger number of patients is warranted to investigate the relation between the primary site of the lymphoma, i.e. extranodal intestinal, extranodal extraintestinal, or nodal intestinal, and (its impact on) clinical presentation and prognosis.

Adult↗

Elementary identification of a gnathosonic classification using an autoregressive model.

This was an investigation to determine the feasibility of an autoregressive (AR) model for establishing characteristic parameters from recorded occlusal sounds and develop their classification. Thirty four normal subjects with intact natural dentitions were selected for the study. The subjects' occlusal sounds from both sides of their faces respectively were sampled, and the gnathosonic classification (Class A, B and C) was established by observing the original recorded wave pattern and measuring the duration. Then, a 20 order AR model was calculated with the collected data, and the AR model coefficients were found to be similar to the indices of Bayes' discriminatory analysis. The total conformation rates of the modelled left and right occlusal sounds to the classification, estimated by Bayes' discriminant functions were 97.06% and 88.24% respectively. AR coefficients representing the characteristics of human occlusal sounds can be helpful in their classification and allow computer diagnosis of occlusal disorders.

Acoustics↗

Molecular phylogenetics of the Macaronesian-endemic genus Bystropogon (Lamiaceae): palaeo-islands, ecological shifts and interisland colonizations.

Abstract A molecular phylogenetic study of Bystropogon L'Her. (Lamiaceae) is presented. We performed a cladistic analysis of nucleotide sequences of the internal transcribed spacers (ITS), of the nuclear ribosomal DNA, and of the trnL gene and trnL-trnF intergenic spacer of the chloroplast DNA. Bystropogon odoratissimus is the only species endemic to the Canary Islands that occurs in the three palaeo-islands of Tenerife. This species is not part of an early diverging lineage of Bystropogon and we suggest that it has a recent origin. This phylogenetic pattern is followed by most of the species endemic to the palaeo-islands of Tenerife. The two sections currently recognized in Bystropogon form two monophyletic groups. Taxa belonging to the section Bystropogon clade show interisland colonization limited to the Canary Islands with ecological shifts among three ecological zones. Taxa from the section Canariense clade show interisland colonization both within the Canary Islands and between the Canary Islands and Madeira. Speciation events within this clade are mostly limited to the laurel forest. The genus has followed a colonization route from the Canaries towards Madeira. This route has also been followed by at least five other plant genera with species endemic to Macaronesia. Major incongruences were found between the current infrasectional classification and the molecular phylogeny, because the varieties of Bystropogon origanifolius and Bystropogon canariensis do not form two monophyletic groups. The widespread B. origanifolius appears as progenitor of the other species in section Bystropogon with a more restricted distribution.

DNA, Chloroplast↗

Immunohistochemical studies on myoepithelial changes in breast tumors.

Specific rabbit antisera directed against human uterine myosin were prepared and used for immunohistochemical studies on myoepithelial cells (MECs) in some breast tumors. In fibroadenomas, MECs were observed confined to the periductal portions but not in the stroma. In infiltrating duct carcinomas, MECs were also present as a distinctive periductal layer. Moreover, they were also seen in the infiltrating area, either associated with a small nest of carcinoma cells or freely in the stroma. Larger nests of medullary carcinomas usually were not accompanied by any layer of MECs. No MECs were detected in lobular carcinomas as far as the infiltrating area was concerned. It is suggested from these results that the behavior of MECs is significantly different, depending upon the types of breast tumors. It also appears that the present method may be useful for further analysis of the origin and growth pattern in various breast tumors.

Adenofibroma↗

Comparative aspects of cerebral cortical development.

This review aims to provide examples of how both comparative and genetic analyses contribute to our understanding of the rules for cortical development and evolution. Genetic studies have helped us to realize the evolutionary rules of telencephalic organization in vertebrates. The control of the establishment of conserved telencephalic subdivisions and the formation of boundaries between these subdivisions has been examined and the very specific alterations at the striatocortical junction have been revealed. Comparative studies and genetic analyses both demonstrate the differential origin and migratory pattern of the two basic neuron types of the cerebral cortex. GABAergic interneurons are mostly generated in the subpallium and a common mechanism governs their migration to the dorsal cortex in both mammals and sauropsids. The pyramidal neurons are generated within the cortical germinal zone and migrate radially, the earliest generated cell layers comprising preplate cells. Reelin-positive Cajal-Retzius cells are a general feature of all vertebrates studied so far; however, there is a considerable amplification of the Reelin signalling with cortical complexity, which might have contributed to the establishment of the basic mammalian pattern of cortical development. Based on numerous recent observations we shall present the argument that specialization of the mitotic compartments may constitute a major drive behind the evolution of the mammalian cortex. Comparative developmental studies have revealed distinct features in the early compartments of the developing macaque brain, drawing our attention to the limitations of some of the current model systems for understanding human developmental abnormalities of the cortex. Comparative and genetic aspects of cortical development both reveal the workings of evolution.

Animals↗

Pulsatile secretion of pregnancy-associated plasma protein-A (PAPP-A) in non-pregnant women.

No changes in PAPP-A levels could be detected when plasma samples were obtained every second day throughout the entire menstrual cycle in three healthy women. But when measured every 30 min throughout 12 consecutive hours, in four healthy women, PAPP-A followed a pulsatile pattern which may originate in the endometrium since no PAPP-A pulses were detected in a long-term hysterectomized woman, or in two men. The pulses were not related to levels of oestradiol, progesterone, FSH or LH.

Adult↗

Exploring scale-dependent correlations between cancer mortality rates using factorial kriging and population-weighted semivariograms.

This paper presents a geostatistical methodology which accounts for spatially varying population size in the processing of cancer mortality data. The approach proceeds in two steps: (1) spatial patterns are first described and modeled using population-weighted semivariogram estimators, (2) spatial components corresponding to nested structures identified on semivariograms are then estimated and mapped using a variant of factorial kriging. The main benefit over traditional spatial smoothers is that the pattern of spatial variability (i.e. direction-dependent variability, range of correlation, presence of nested scales of variability) is directly incorporated into the computation of weights assigned to surrounding observations. Moreover, besides filtering the noise in the data the procedure allows the decomposition of the structured component into several spatial components (i.e. local versus regional variability) on the basis of semivariogram models. A simulation study demonstrates that maps of spatial components are closer to the underlying risk maps in terms of prediction errors and provide a better visualization of regional patterns than the original maps of mortality rates or the maps smoothed using weighted linear averages. The proposed approach also attenuates the underestimation of the magnitude of the correlation between various cancer rates resulting from noise attached to the data. This methodology has great potential to explore scale-dependent correlation between risks of developing cancers and to detect clusters at various spatial scales, which should lead to a more accurate representation of geographic variation in cancer risk, and ultimately to a better understanding of causative relationships.

Journal Article↗

Stable isotope analyses of heroin seized from the merchant vessel Pong Su.

A new type of heroin HCl seized in Australia was examined by stable isotope analysis. The final origin/process classification of these samples by chromatographic signature profiles of the impurity/manufacturing by-products was previously determined to be "unknown" by two independent national laboratories. Various drug enforcement authorities speculated that the heroin might be from a new region or new illicit process due to the unusual chromatographic impurity profiles that were present. Samples from 20 different kilogram packages were examined for isotopic content to determine if the samples fit isotopic patterns of known origins or if they were unique to any known origins. Authentic specimens from Southeast Asian (N=59), Southwest Asia (N=37), South America (N=104), and Mexico (N=21) we concomitantly examined for comparison purposes. Both continuous flow elemental analysis-isotope ratio mass spectrometry and gas chromatography-isotope ratio mass spectrometry techniques were utilized. Heroin samples were also converted to morphine, without apparent isotopic fractionation, utilizing methanolic HCl for gas chromatography-isotope ratio mass spectrometry. The Pong Su samples were found to be isotopically and isotopically/alkaloidally distinct from the known origin/process classifications of Southwest Asian, Southeast Asian, South American, and Mexican.

Journal Article↗

S phase of the cell cycle.

In each cell cycle the complex structure of the chromosome must be replicated accurately. In the last few years there have been major advances in understanding eukaryotic chromosome replication. Patterns of replication origins have been mapped accurately in yeast chromosomes. Cellular replication proteins have been identified by fractionating cell extracts that replicate viral DNA templates in vitro. Cell-free systems that initiate eukaryotic DNA replication in vitro have demonstrated the importance of complex nuclear architecture in the control of DNA replication. Although the events of S phase were relatively neglected for many years, knowledge of DNA replication is now advancing rapidly in step with other phases of the cell cycle.

Animals↗

Bacterial degradation of ring-chlorinated acetophenones.

Two strains, Alcaligenes sp. strain ACA and Pseudomonas fluorescens ACB, isolated from acetophenone and 4'-hydroxyacetophenone enrichments, respectively, cometabolize a range of chlorinated acetophenones (CAs). A biological Baeyer-Villiger reaction converts the CA to chlorophenyl acetate. This is evident only in the presence of an esterase inhibitor, since the CA is normally rapidly hydrolyzed to a chlorophenol which has the same substitution pattern as the original ketone. The oxygenase that attacks the ketone uses NADPH in the incorporation of one atom of O(2) and is strongly inhibited by phenols that bear an ortho or meta chlorine or bromine, but much less by cresols or phenol itself. A feedback phenomenon may thus account for the inability of strain ACA to grow on CAs, which also fail to induce the cells for their own metabolism.

Journal Article↗

Degradation of 2-methylbenzoic acid by Pseudomonas cepacia MB2.

We report the isolation of Pseudomonas cepacia MB2, believed to be the first microorganism to utilize 2-methylbenzoic acid as the sole carbon source. Its growth range included all mono- and dimethylbenzoates (with the exception of 2,5- and 2,6-dimethylbenzoates) and 3-chloro-2-methylbenzoate (but not 4- or 5-chloro-2-methylbenzoate) but not chlorobenzoates lacking a methyl group. 2-Chlorobenzoate, 3-chlorobenzoate, and 2,3-, 2,4-, and 3,4-dichlorobenzoates inhibited growth of MB2 on 2-methylbenzoate as a result of cometabolism to the corresponding chlorinated catechols which blocked the key enzyme catechol 2,3-dioxygenase. A metapyrocatechase-negative mutant, MB2-G5, showed accumulation of dimethylcatechols from 2,3- and 3,4-dimethylbenzoates, and phenols were detected in resting-cell transformation extracts bearing the same substitution pattern as the original substrate, presumably following thermal degradation of the intermediate dihydrodiol. 2-Methylphenol was also found in extracts of the mutant cells with 2-methylbenzoate. These observations suggested a major route of methylbenzoate metabolism to be dioxygenation to a carboxy-hydrodiol which then forms a catechol derivative. In addition, the methyl group of 2-methylbenzoate was oxidized to isobenzofuranone (by cells of MB2-G5) and to phthalate (by cells of a separate mutant that could not utilize phthalate, MB2-D2). This pathway also generated a chlorinated isobenzofuranone from 3-chloro-2-methylbenzoate.

Benzoates↗