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PubMed2004

Genetic and plasma markers of venous thromboembolism in patients with high grade glioma.

PURPOSE: Deep venous thrombosis/pulmonary embolism (DVT/PE) is a frequent complication in the course of cancer, particularly in brain tumors. We investigated genetic and plasma factors possibly associated with risk of DVT/PE in patients with high-grade glioma. EXPERIMENTAL DESIGN: In a case-control study, we studied polymorphisms of the genes coding for factor II (G20210A), factor V (G1691A), methylenetetrahydrofolate-reductase (C677T), tissue-type plasminogen activator (tPA; insertion/deletion), plasminogen activator inhibitor-1 (PAI-1; 4G/5G), and vascular endothelial growth factor (VEGF; C936T). We also measured plasma levels of D-dimer, lipoprotein (lp) (a), homocysteine, VEGF, tPA, and PAI-1, comparing healthy control patients with patients with glioma or with patients with neurological nonneoplastic disease (multiple sclerosis). RESULTS: Genotype frequencies of polymorphisms analyzed were similar in patients with glioma and in healthy matched population. D-dimer, lp (a), homocysteine, VEGF, tPA, and PAI-1 plasma levels were significantly higher in patients with glioma than in healthy controls, whereas patients having neurological nonneoplastic disease had plasma values of these molecules not significantly different from healthy controls. VEGF, tPA, and PAI-1 were also found at high-plasma levels in patients carrying genotypes that, in healthy controls, were associated with "low-producing" phenotypes. CONCLUSIONS: Genetic risk factors alone did not explain the high incidence of DVT/PE observed in patients with glioma. Higher plasma levels of molecules influencing the coagulation pathways indicate that the tumor itself might confer an increased risk of DVT/PE; thus, D-dimer, homocysteine, lp (a), VEGF, tPA, and PAI-1 look like good candidates to be evaluated as DVT/PE prognostic factors.

Brain Neoplasms↗
PubMed2003

Evolution of the bacterial species Lactobacillus delbrueckii: a partial genomic study with reflections on prokaryotic species concept.

The species Lactobacillus delbrueckii consists at present of three subspecies, delbrueckii, lactis and bulgaricus, showing a high level of DNA-DNA hybridization similarity but presenting markedly different traits related to distinct ecological adaptation. The internal genetic heterogeneity of the bacterial species L. delbrueckii was analyzed. Phenotypic and several genetic traits were investigated for 61 strains belonging to this species. These included 16S rDNA sequence mutations, expression of beta-galactosidase and of the cell wall-anchored protease, the characterization of the lactose operon locus and of the sequence of lacR gene, galactose metabolism, and the distribution of insertion sequences. The high genetic heterogeneity of taxa was confirmed by every trait investigated: the lac operon was completely deleted in the subsp. delbrueckii, different mutation events in the repressor gene of the operon led to a constitutive expression of lacZ in the subsp. bulgaricus. Structural differences in the same genetic locus were probably due to the presence of different IS elements in the flanking regions. The different expression of the cell wall-anchored protease, constitutive in the subsp. bulgaricus, inducible in the subsp. lactis, and absent in the subsp. delbrueckii was also a consequence of mutations at the gene level. The galT gene for galactose metabolism was found only in the subsp. lactis, while no specific amplification product was detected in the other two subspecies. All these data, together with the absence of a specific IS element, ISL6, from the major number of strains belonging to the subsp. bulgaricus, confirmed a deep internal heterogeneity among the three subspecies. Moreover, this evidence and the directional mutations found in the 16S rDNA sequences suggested that, of the three subspecies, L. delbrueckii subsp. lactis is the taxon closer to the ancestor. Limitations of the current prokaryotic species definition were also discussed, based on presented evidences. Our results indicate the need for an accurate investigation of internal heterogeneity of bacterial species. This study has consequences on the prokaryotic species concept, since genomic flexibility of prokaryotes collides with a stable classification, necessary from a scientific and applied point of view.

Amino Acid Sequence↗
PubMed2025

Q RadFusion: Hybrid Quantum Classical Radiogenomic Framework for Breast Cancer Diagnosis.

BACKGROUND AND PURPOSE: Breast cancer remains the most common cancer in women worldwide, with early and accurate diagnosis critical for patient survival. Radiogenomics integrates imaging phenotypes with genomic profiles, offering a pathway to precision diagnostics. However, existing classical machine learning models often struggle with the high dimensionality and heterogeneity of multimodal data, leading to issues in calibration and reproducibility. This study presents Q RadFusion, a hybrid quantum-classical framework designed to enhance breast cancer diagnosis by fusing mammography and genomics data. METHODS: Q RadFusion was implemented on two publicly available datasets: CBIS-DDSM (2,600 curated mammography cases, TCIA) and TCGA-BRCA (1,000 genomic profiles, GDC). Imaging preprocessing included bias-field correction, segmentation, and harmonization, while genomic data underwent normalization and imputation. Feature selection was performed using the Quantum Approximate Optimization Algorithm (QAOA), and features were mapped into a quantum Hilbert space using Variational Quantum Circuits (VQC). For multimodal fusion, ResNet encoded mammography features, and a Transformer encoded genomic features. Patient-level and site-held-out splits were used for evaluation. RESULTS: Q RadFusion achieved an AUC of 0.96 and accuracy of 94%, outperforming baselines including CNN-LSTM, ResNet + XGBoost, and multimodal Transformers. Ablation studies confirmed the contribution of quantum components, with optimal performance observed at circuit depth, qubits, and QAOA layers. The model also demonstrated improved calibration and ~ 80% fewer parameters compared to deep fusion networks. CONCLUSION: Q RadFusion demonstrates that hybrid quantum-classical radiogenomic integration can deliver accurate, reproducible, and clinically meaningful diagnostic support for breast cancer, with strong potential for future clinical translation.

Breast Cancer↗
PubMed1998

Class II Division 2 malocclusion: a heritable pattern of small teeth in well-developed jaws.

Angle's designation of the Class II Division 2 (II/2) malocclusion recognizes a unique combination of overbite, incisor retroclination, and sagittal discrepancy. A very severe II/2 phenotype, characterized by concealment of the mandibular incisors in occlusion, has been called Deckbiss in German, or cover-bite. In this report, the cover-bite malocclusion is studied to identify morphological factors associated with Angle's II/2 occlusal discrepancy. Selected X-ray cephalometric and odontometric measurements were recorded for 23 subjects (M14; F9) with II/2 cover-bite malocclusion. Data were compared with those from a control-reference sample of 537 individuals. Cephalometrically, the II/2 cover-bite sample showed a pattern of strong vertical posterior development of the mandible with forward-rotation and skeletofacial hypodivergence (p < 0.0001). Anteroposteriorly, the maxillomandibular dentoalveolar relationship was relatively normal, and the basal bone region of the mandibular corpus appeared significantly well developed anteriorly, accounting for excessive bony chin projection (p < 0.0001). Dentally, mesiodistal tooth diameters for the maxillary and mandibular incisors of the II/2 cover-bite sample were significantly smaller than those of the reference sample (p < 0.002), pointing to systematically reduced tooth-size as a trait associated with II/2 malocclusion. These findings of a characteristic pattern of heritable skeletal and tooth-size features in II/2 cover-bite malocclusion indicate the presence of strong genetic influences in the formation of Angle's II/2 deep-bite discrepancy.

Adolescent↗
PubMed1993

A case of protein C deficiency associated with cerebral infarction and obstruction of deep leg and inferior mesenteric veins.

Protein C, a vitamin K-dependent protein, is a blood coagulation inhibitor. Its deficiency causes systemic thrombosis. A 31-year-old woman developed cerebral infarction followed by late psychomotor seizures, and thrombosis in the inferior mesenteric vein and bilateral crural veins. Her parents were first cousins. Her mother died of cerebral thrombosis in her 30's. Her elder brother died of suspected purpura fulminans immediately after birth. Her protein C activity and protein C antigen level decreased markedly and were less than 5% of those of normal controls and 0.3 microgram/ml, respectively. Her father, a paternal aunt and a maternal uncle also showed a low protein C activity and protein C antigen level. This patient seems to have congenital protein C deficiency which produced thrombosis in the leg veins and the mesenteric vein, probably cerebral infarction.

Adult↗
PubMed2002

Desulfobulbus mediterraneus sp. nov., a sulfate-reducing bacterium growing on mono- and disaccharides.

A new sulfate-reducing bacterium, strain 86FS1, was isolated from a deep-sea sediment in the western Mediterranean Sea with sodium lactate as electron and carbon source. Cells were ovoid, gram-negative and motile. Strain 86FS1 contained b- and c-type cytochromes. The organism was able to utilize propionate, pyruvate, lactate, succinate, fumarate, malate, alanine, primary alcohols (C(2)-C(5)), and mono- and disaccharides (glucose, fructose, galactose, ribose, sucrose, cellobiose, lactose) as electron donors for the reduction of sulfate, sulfite or thiosulfate. The major products of carbon metabolism were acetate and CO(2), with exception of n-butanol and n-pentanol, which were oxidized only to the corresponding fatty acids. The growth yield with sulfate and glucose or lactate was 8.3 and 15 g dry mass, respectively, per mol sulfate. The temperature limits for growth were 10 degrees C and 30 degrees C with an optimum at 25 degrees C. Growth was observed at salinities ranging from 10 to 70 g NaCl l(-1). Sulfide concentrations above 4 mmol l(-1) inhibited growth. The fatty acid pattern of strain 86FS1 resembled that of Desulfobulbus propionicus with n-14:0, n-16:1omega7, n-16:1 omega5, n-17:1 omega6 and n-18:1 omega7 as dominant fatty acids. On the basis of its phylogenetic position and its phenotypic properties, strain 86FS1 affiliates with the genus Desulfobulbus and is described as a new species, Desulfobulbus mediterraneus sp. nov.

Deltaproteobacteria↗
PubMed2003

Isolation of neural stem cells from the forebrain of deceased early postnatal and adult rats with protracted post-mortem intervals.

Neural stem cells were isolated from deceased early postnatal and adult rats with varying post-mortem intervals. Animals were killed by deep anesthesia and stored in a refrigerator at 4 degrees C for 1-6 days before use. Neurospheres were obtained from the forebrain tissue, including the lateral ventricle in the early postnatal rats, and from the striatal wall of lateral ventricle, including the subventricular zone (SVZ) in adult rats. The number of neurospheres obtained in the primary culture from early postnatal animals was much larger than that from the adult rats. There was no significant difference in the population of neurospheres between the living and the deceased animals at least within 2 days after death. A few neurospheres were still obtainable at 6 days after death in early postnatal animals, but almost no neurospheres were obtained at 5 days after death in the adult rats. The differentiation capacity of neural stem cells in neurospheres was similar between the deceased and the living animals. The rich vascular bed in the SVZ of the lateral ventricle suggests that the vascular architecture might be in part responsible for the survival of the neural stem cells in the deceased animals. Neurosphere cells derived from deceased adult rats survived and differentiated mainly into glial cells in the host spinal cord tissue after transplantation into the injured spinal cord. Therefore, the neural stem cells from deceased animals express the same phenotypes as those from living animals in terms of neurosphere formation, proliferation, and differentiation at least 2 days after death. The neural stem cells from cadavers have great significance in terms of their clinical use as homografts for CNS regeneration.

Animals↗
PubMed1993

In situ detection of PCR-amplified HIV-1 nucleic acids and tumor necrosis factor cDNA in cervical tissues.

This study determined the histological distribution of polymerase chain reaction-amplified human immunodeficiency virus 1 (HIV-1) DNA and RNA in cervical tissues. Amplified HIV-1 DNA and complementary DNA were detected in each of 21 cervical biopsies from women with acquired immunodeficiency syndrome. The viral nucleic acids were most abundant in the endocervical aspect of the transformation zone at the interface of the glandular epithelium and the submucosa and in the deep submucosa around microvessels. Many virally infected cells colabeled with leukocyte common antigen, Mac387, and polymerase chain reaction-amplified tumor necrosis factor complementary DNA, demonstrating that they were activated macrophages. Virally amplified nucleic acids were not detected in 10 controls and in only one of eight cervical tissues from children less than 3 years of age who died due to immunodeficiency syndrome acquired in utero. Determining whether the HIV-1-infected macrophages consistently present in the cervix of adult seropositive women may represent primary infection and, if so, whether they can transport the virus to regional lymph nodes and thus initiate systemic infection requires further study.

Adult↗
PubMed1995

Analysis and clinical implications of K-ras gene mutations and infection with human papillomavirus types 16 and 18 in primary adenocarcinoma of the uterine cervix.

Experimental models indicate that activated ras genes and HPV oncogenic sequences may cooperate in inducing a completely transformed phenotype in epithelial cells. We searched for K-ras gene mutations and HPV type-16 and -18 sequences in 67 primary adenocarcinomas of the uterine cervix by analyzing DNAs from formalin-fixed, paraffin-embedded tissue samples. Target sequences were amplified by PCR and analyzed by denaturing gradient gel electrophoresis (DGGE) and sequencing for the detection of K-ras gene mutations and by Southern blotting for the detection of HPV infection. We found 16 mutations in 15 cases; 14 were at codon 12 and 2 at codon 13; 11 were base transitions and 5 were transversions. Mutations were more frequent in mucin-secreting than in non-mucinous tumors. HPV oncogenic sequences were detected in 58 cases with no significant difference between K-ras-mutated and wild-type tumors. HPV oncogenic sequences were also more frequent in mucin-secreting than in non-mucinous tumors. Both molecular events were present simultaneously in 13 out of 58 cases, all of which had histologically grade-2 and grade-3 tumors. Clinico-pathological parameters of the disease and the overall survival, however, were independent of K-ras mutations and of HPV-16 and -18 infection, as shown by univariate and multivariate analysis. In contrast, stage of disease, lymph-node metastases, deep infiltration, clear-cell histology and low grade of differentiation were risk factors for tumor-related death.

Adenocarcinoma↗
PubMed2005

Bacillus alveayuensis sp. nov., a thermophilic bacterium isolated from deep-sea sediments of the Ayu Trough.

Two thermophilic, spore-forming strains, TM1(T) and TM5, were isolated from deep-sea sediment (4000 m below sea level) of the Ayu Trough in the western Pacific Ocean. Cells of the two strains were Gram-positive, motile and rod-shaped. Their spores were ellipsoidal, subterminal to terminal and occurred in swollen sporangia. The two strains grew at temperatures up to 65 degrees C and in the pH range 6.5-9.0. The NaCl concentration for optimal growth was 3.0 % (w/v) and growth was inhibited by 5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains TM1(T) and TM5 belonged to the genus Bacillus, and that strain TM1(T) was most closely related to Bacillus aeolius DSM 15084(T) (96.7 %), Bacillus smithii DSM 4216(T) (96.1 %), Bacillus methanolicus NCIMB 13113(T) (95.8 %) and Bacillus pallidus DSM 3670(T) (95.7 %). Between the 16S rRNA gene sequences of strains TM1(T) and TM5 there were only three nucleotide differences, implying that the two strains were of the same species. The cellular fatty acid profiles of the two strains were also very similar, with iso-C(15 : 0), iso-C(16 : 0), C(16 : 0), iso-C(17 : 0) and anteiso-C(17 : 0) as the major components. The G + C content of strain TM1(T) was 38.7 %. On the basis of phenotypic and molecular data, strains TM1(T) and TM5 represent a novel species of the genus Bacillus, for which the name Bacillus alveayuensis sp. nov. is proposed. The type strain is TM1(T) (= KCTC 10634(T) = JCM 12523(T)).

Bacillus↗
PubMed1999

Clinical features and revised diagnostic criteria in Joubert syndrome.

The clinical presentation of children with Joubert syndrome can include nonspecific features such as hypotonia, ataxia, and developmental delay. Careful examination of the face shows a characteristic appearance, and a neuro-ophthalmologic examination shows the presence of oculomotor apraxia. In the neonatal period, most children have hyperpnea intermixed with central apnea. Neuroimaging of the head in the axial plane demonstrates the "molar tooth sign"--deep posterior interpeduncular fossa, thick and elongated superior cerebellar peduncles, and hypoplastic or aplastic superior cerebellar vermis. The central nervous system malformation spectrum observed in radiologic and neuropathologic studies accounts for many clinical features of Joubert syndrome. The developmental delay and cognitive impairment cannot be fully explained by the hindbrain malformation and probably result from dysfunction of the cerebral hemispheres. Although related conditions with vermian hypoplasia or aplasia (including Arima; Senior-Loken; and cerebellar vermian hypoplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis syndromes) can mimic Joubert syndrome, detailed imaging data are lacking in such cases. We propose a revision in diagnostic criteria for Joubert syndrome.

Abnormalities, Multiple↗
PubMed2004

Thermococcus marinus sp. nov. and Thermococcus radiotolerans sp. nov., two hyperthermophilic archaea from deep-sea hydrothermal vents that resist ionizing radiation.

Enrichments for anaerobic, organotrophic hyperthermophiles were performed with hydrothermal chimney samples collected from the Mid-Atlantic Ridge at a depth of 3,550 m (23 degrees 22'N, 44 degrees 57'W) and the Guaymas Basin (27 degrees 01'N, 111 degrees 24'W) at a depth of 2,616 m. Positive enrichments were submitted to gamma-irradiation at doses of 20 and 30 kGy. Two hyperthermophilic, anaerobic, sulfur-metabolizing archaea were isolated. Strain EJ1T was isolated from chimney samples collected from the Mid-Atlantic Ridge after gamma-irradiation at 20 kGy, and strain EJ2T was isolated from the Guaymas Basin after gamma-irradiation at 30 kGy. Only strain EJ2T was motile, and both formed regular cocci. These new strains grew between 55 and 95 degrees C with the optimal temperature being 88 degrees C. The optimal pH for growth was 6.0, and the optimal NaCl concentration for growth was around 20 g l(-1). These strains were obligate anaerobic heterotrophs that utilized yeast extract, tryptone, and peptone as a carbon source for growth. Ten amino acids were essential for the growth of strain EJ1), such as arginine, aspartic acid, isoleucine, leucine, methionine, phenylalanine, proline, threonine, tyrosine, and valine, while strain EJ2T was unable to grow on a mixture of amino acids. Elemental sulfur or cystine was required for EJ2T growth and was reduced to hydrogen sulfide. Rifampicin inhibited growth for both strains EJ1T and EJ2T. The G + C contents of the genomic DNA were 52.3 and 54.5 mol% for EJ1T and EJ2T, respectively. As determined by 16S rRNA gene sequence analysis, these strains were more closely related to Thermococcus gorgonarius, T. celer, T. guaymasensis, T. profundus, and T. hydrothermalis. However, no significant homology was observed between them with DNA-DNA hybridization. These novel organisms also possess phenotypic traits that differ from those of its closest phylogenetic relatives. Therefore, it is proposed that these isolates, which are amongst the most radioresistant hyperthermophilic archaea known to date with T. gammatolerans (Jolivet et al. 2003a), should be described as novel species T. marinus sp. nov. and T. radiotolerans sp. nov. The type strain of T. marinus is strain EJ1T (= DSM 15227T = JCM 11825T) and the type strain of T. radiotolerans is strain EJ2T (= DSM 15228T = JCM 11826T).

Base Composition↗
PubMed2002

The physiology and collective recalcitrance of microbial biofilm communities.

Microbial biofilms impinge upon all aspects of our lives. Whilst much of this impact is positive, there are many areas in which the presence and activities of biofilms are regarded as problematic and in need of control. It is in this respect that biofilms reveal their recalcitrance towards many of the long-established antibiotics, and industrial and medical treatment strategies. The nature of the resistance of biofilms, in spite of much research, remains an enigma. Whilst it is recognized that reaction--diffusion limitation properties of the biofilm matrix towards the majority of treatment agents will impede access, this cannot be the sole explanation of the observed resistance. Rather, it will delay the death of cells within the community to various extents. Similarly, it is recognized that biofilm communities are phenotypically heterogeneous and that their eradication will reflect the susceptibility of the most resistant phenotype. The nutrient and gaseous gradients that generate this heterogeneity will, however, be destroyed as a result of antimicrobial treatments and cause the phenotype of the survivors to alter from slow-growing resistant cells to fast-growing susceptible ones. Accordingly both explanations can only delay death of the community. In order to explain more fully the long-term recalcitrance of biofilms towards such a wide variety of biocidal agents, more radical hypotheses must be considered. Amongst these are that multidrug efflux pumps could be up-regulated on expression of a biofilm phenotype. Whilst this is an appealing and simple explanation, because of its ability to explain the breadth of agents to which biofilms are resistant, recent work has suggested that this is not the case. Alternative hypotheses attempt to explain the diversity of agents by invoking a common cause of death for which singular resistance mechanisms could be applied. It is therefore suggested that an altruistic majority of sublethally damaged cells in a population commit suicide (apoptosis), thereby providing some protection to the survivors. A proportion of cells (persisters) is suggested to be defective, or repressed, in their suicide response, and survive. The persisters thereby benefit from the self-sacrifice of their compatriots and maintain the gene pool. A second explanation of the presence of persisters is that the general stress response, well known to include the adoption of a viable, nonculturable state of quiescence, is up-regulated in small pockets of the biofilm community, where nutrients are particularly scarce. Such quiescent cells noted for their resistance towards the metabolically acting biocides would potentially have their dormancy broken after treatment by the replenished supply of nutrients caused by the death of the majority. A more recent hypothesis suggests that extracellular signals, 'alarmones', released from killed cells might prime recipients into a state of resistance. Thus, in biofilm communities deep lying cells might be alerted into a resistant state by the premature death of peripheral cells. It is equally possible that 'alarmones', in this context, are merely the post-treatment 'wake-up' call to a previously quiescent subset of cells. In this review, we attempt to provide a holistic view of the potential mechanisms by which biofilms express resistance. Since these mechanisms are multifaceted then their impact upon resistance will be considered against the context of biofilm formation, growth and maturation.

Bacteria↗
PubMed1989

Characterization of HTLV-I isolates and T lymphoid cell lines derived from French West Indian patients with tropical spastic paraparesis.

Lymphoid cell lines derived from the peripheral blood of French West Indian patients with HTLV-I sero-positive Tropical Spastic Paraparesis and HTLV-I isolates were characterized. While patients' peripheral blood lymphocytes did not express detectable HTLV-I antigens when uncultured, they did so after short-term culture. Established cell lines were of T-cell lineage: CD2+, CD3+, CD4+, CD7+, WT31+ with activated T-cell markers CD25+, DR+ and a clonal rearrangement of the beta and gamma genes of the T-cell receptor. HTLV-I antigens were detected in cell lines by indirect immunofluorescence, Western blot and radio-immunoprecipitation assays. After 4 months in culture, low levels of Mg2+ dependent reverse transcriptase activity were detected and electron microscopy revealed numerous type-C retroviral particles similar to HTLV-I virions. Western blot and radio-immunoprecipitation analysis of purified viruses revealed gp46, p24, p19 and Pr53gag proteins similar to those detected in HUT 102 and MT2 cell lines. Deep analysis of env-coded precursor of one TSP versus ATL isolates revealed minor differences in their molecular weights. Southern blot analysis using 32P HTLV-I env gene as a probe showed the presence of HTLV-I proviral fragments clonally integrated into the genome of the cell lines. Our data suggest that HTLV-I isolated from Tropical Spastic Paraparesis does not differ significantly from the leukemogenic prototypes. Does HTLV-I induce either acute lymphoproliferative diseases or chronic neuromyelopathies depending upon as yet unknown co-factors? This question remains to be determined.

Blotting, Southern↗
PubMed2007

Protein C -1641 AA is associated with decreased survival and more organ dysfunction in severe sepsis.

OBJECTIVE: Protein C contains an A/G polymorphism at position -1641 and a C/T polymorphism at -1654 associated with risk of deep venous thrombosis. We tested the hypothesis that these polymorphisms are associated with altered outcome in patients having severe sepsis, in which protein C is a central molecule. DESIGN: Prospective cohorts, gene-association study. SETTING: Tertiary care medical/surgical intensive care unit. PATIENTS: We first recruited a derivation cohort of patients having severe sepsis (n = 62). A second replication cohort was similarly defined but larger (n = 402). We tested for biological plausibility in a third cohort of post-cardiopulmonary bypass patients (n = 61). INTERVENTIONS: Patients were genotyped at protein C -1641 and -1654. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was survival in cohorts 1 and 2 and postoperative serum interleukin-6 concentration in cohort 3. Severity of individual organ dysfunctions and systemic inflammation were secondary outcome variables. In the first derivation cohort, the protein C -1641 AA genotype was associated with decreased 28-day survival (p < .05). This finding was confirmed in the much larger replication cohort of patients having severe sepsis (p = .028). In addition, the protein C -1641 AA genotype was associated with significantly more organ dysfunction and more clinical evidence of systemic inflammation (p < .05). Furthermore, the -1641 AA genotype was associated with increased serum interleukin-6 at 4 and 24 hrs after cardiopulmonary bypass (p = .024). There was no association of -1654 A/G with phenotype in any cohort. CONCLUSIONS: Protein C -1641 AA genotype is associated with decreased survival, more organ dysfunction, and more systemic inflammation in patients having severe sepsis and with increased interleukin-6 levels after cardiopulmonary bypass surgery.

APACHE↗
PubMed1994

Inverted pyramidal neurons and interneurons in cat cortical subplate zone are labelled by monoclonal antibody SP1.

During development, the subplate zone of the cat neocortex contains neuronal populations with distinct morphological and neurochemical phenotypes. A subset of those are specifically recognized by a mouse monoclonal antibody termed SUBPLATE-1 (SP1), which was generated against tissue homogenates of kitten cortical white matter. SP1 stains cell bodies and proximal dendrites, but rarely distal dendrites, axonal arbors or spines. In order to characterize morphologically the SP1 immunoreactive subplate cell types, we combined SP1 immunohistochemistry with intracellular iontophoretic injections of Lucifer yellow. The majority of double-labelled neurons were inverted pyramids with a single thicker spine-covered dendrite that descended into the white matter and a tuft of thinner spinous dendrites that ascended from the upper somatic pole, but generally remained confined to the white matter. Other double-labelled neurons were multipolar to bitufted, although often equipped with one thicker descending dendrite. In inverted pyramidal cells, the axons originated from the descending dendrite or, more rarely, from the lower portion of the soma, and descended into the white matter. They formed collaterals recurring toward the grey matter. The presence of dendritic spines on double-labelled pyramidal cells and the axonal arborization patterns were two novel features not revealed previously by SP1 immunohistochemistry alone. The inverted pyramidal morphology was typical for double-labelled neurons located in the subplate zone below the apices of the gyri, whereas those located below the flanks or sulci or deep in the white matter often displayed a bitufted or multipolar spinous morphology. A minority of the double-labelled neurons were multipolar with smooth dendrites and locally branching axons. These results suggest that in the cat subplate zone, a majority of the cells expressing the SP1 antigen are spinous, and we termed the spinous subplate cells 'subplate pyramidal neurons'.

Animals↗
PubMed1993

Use of a reporter gene to follow high-pressure signal transduction in the deep-sea bacterium Photobacterium sp. strain SS9.

Photobacterium sp. strain SS9 is a deep-sea bacterium which modulates the abundances of several outer membrane proteins as a function of hydrostatic pressure. These proteins include the product of the previously cloned ompH gene (D. H. Bartlett, M. Wright, A. A. Yayanos, and M. Silverman. Nature (London) 342:572-574, 1989). Subsequent to conjugal plasmid delivery it was possible to cross an ompH::lacZ transcriptional fusion into the genome of SS9, replacing the wild-type ompH gene, generating strain EC10. EC10 is not impaired in growth at high pressure, indicating that under the growth conditions employed, OmpH is not required for baroadaptation. beta-Galactosidase production in EC10 is induced by high pressure to approximately the same extent that OmpH production is in the parental strain, SS9. Therefore, OmpH abundance appears to be primarily regulated at the transcriptional level. EC10 was used for the isolation of ompH regulatory mutants. Derivatives of EC10 which produce reduced levels of beta-galactosidase at both low and high pressure and which appeared to possess mutations outside the ompH::lacZ locus were obtained. All of these regulatory mutants displayed alterations in the high-pressure repression of a second outer membrane protein, designated OmpL, and two of the mutants were also deficient in the high-pressure induction of a third outer membrane protein, designated OmpI. The most dramatic phenotype was present in mutant EC1002, whose growth was extremely barosensitive. EC1002 is the first pressure-sensitive mutant ever isolated. Prolonged incubation of EC1002 at high pressure led to the accumulation of cells with wild-type growth characteristics at high pressure. These cells are suggested to possess suppressor mutations, as they remain deficient in beta-galactosidase production and maintain their high-pressure-adapted phenotype for many generations in the absence of high-pressure selection.

Adaptation, Physiological↗
PubMed2005

Dissection of the sets of genes that control the behavior of biglycan-deficient pre-osteoblasts using oligonucleotide microarrays.

Biglycan (bgn) is a small leucine-rich proteoglycan (SLPR) that is enriched in the extracellular matrix of skeletal tissues. Bgn-deficient mice develop age-related osteopenia with a phenotype that resembles osteoporosis. In order to identify sets of genes that play a key role in the skeletal abnormality, we determined the global gene expression patterns in bgn-deficient (bgn-KO) pre-osteoblasts using oligonucleotide microarray technology. Calvarial cells were harvested from newborn mice and cultured in the presence or absence of BMP-4 for 7 days. The total RNA was purified, labeled and hybridized to Affymetrix chips (U74A), and analyzed with a software program called GeneSpring. Our data suggested that biglycan regulates the activity of osteoblastic progenitors through sets of genes associated with cell cycle, cell growth, and differentiation. The biological outcome from the altered expression of these genes could cause a defect in the quantity and quality of osteoblastic progenitors, which could contribute to the development of age-related osteopenia in bgn-KO mice. Moreover, the data from this approach also revealed that biglycan deficiency affected the genes that control inflammation, immune response, and growth of tumor cells. These are new and unexpected findings that lead to the formation of new paradigms for biglycan function. Based on these findings, we propose that the reduction of this small proteoglycan with aging may increase the risk of infection and autoimmune diseases, impair wound healing, and cause higher incidences of malignancy. This study provides a broad and deep foundation for understanding SLRP function at a more complex level.

Animals↗