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PubMed1999

Quantifying elasticity analysis: how external effectors cause changes to metabolic systems.

The sites of action of external effectors, such as inhibitors or hormones, on metabolic systems can be described qualitatively by elasticity analysis, or quantitatively by regulation analysis. The use of the latter approach has been limited, due to its practical complexity. In this study, we report mathematical relationships that relate the finite changes in system variables (fluxes and metabolite concentrations) to changes in activity of metabolic processes brought about by a single step addition of an effector. The activation or inhibition of a process by an effector is measured from changes in flux and intermediate levels. The changes in activity of each process can be used to describe, semi-quantitatively, which activations or inhibitions of the system processes are important in bringing about the observed levels of system variables.

Elasticity↗
PubMed1986

The influence of hepatic plasma flow on alfentanil plasma concentration plateaus achieved with an infusion model in humans: measurement of alfentanil hepatic extraction coefficient.

In a group of seven patients undergoing intracranial surgery under neurolept anesthesia, an alfentanil infusion was initiated with a loading dose of 235 micrograms/kg over 5 min, followed by a maintenance infusion rate of 1.8 microgram X kg-1 X min-1 in order to obtain a steady state plasma concentration (Css) of 400 ng/ml-1 according to an infusion model. The mean values of Css (446 +/- 209 ng/ml) were close to the predicted ones. Nevertheless, an important intersubject variability in Css values was observed. A positive linear correlation existed between alfentanil steady state clearance and indocyanine green clearance (r = 0.88) and between alfentanil steady state clearance and cardiac index (r = 0.93). In three patients, a catheter was inserted into an hepatic vein to determine the alfentanil hepatic extraction coefficient. Alfentanil plasma clearance did not differ from alfentanil hepatic clearance and alfentanil hepatic extraction coefficient values ranged from 0.32-0.53. We conclude that alfentanil is a drug with an intermediate hepatic extraction coefficient and that alfentanil plasma clearance depends on hepatic plasma flow, which is thus one of the factors accounting for individual variability in plasma concentration plateaus achieved with an infusion model.

Adult↗
PubMed2004

Molecular epidemiology of white spot syndrome virus within Vietnam.

White spot syndrome virus (WSSV), the sole member of the virus family Nimaviridae, is a large double-stranded DNA virus that infects shrimp and other crustaceans. By alignment of three completely sequenced isolates originating from Taiwan (WSSV-TW), China (WSSV-CN) and Thailand (WSSV-TH), the variable loci in the genome were mapped. The variation suggests the spread of WSSV from a common ancestor originating from either side of the Taiwan Strait to Thailand, but support for this hypothesis through analysis of geographical intermediates is sought. RFLP analysis of eight Vietnamese WSSV isolates, of which six were collected along the central coast (VN-central) and two along the south coast (VN-south), showed apparent sequence variation in the variable loci identified previously. These loci were characterized in detail by PCR amplification, cloning and sequencing. Relative to WSSV-TW, all VN-central isolates showed a approximately 8.5 kb deletion in the major variable region ORF23/24, whereas the VN-south isolates contain a deletion of approximately 11.5 or approximately 12.2 kb, compared to a approximately 1.2 or approximately 13.2 kb deletion in WSSV-CN and WSSV-TH, respectively. The minor variable region ORF14/15 showed deletions of various sizes compared with WSSV-TH for all eight VN isolates. The data suggest that the VN isolates and WSSV-TH have a common lineage, which branched off from WSSV-TW and WSSV-CN early on, and that WSSV entered Vietnam by multiple introductions. A model is presented for the spread of WSSV from either side of the Taiwan Strait into Vietnam based on the gradually increasing deletions of both 'variable regions'. The number and order of repeat units within ORF75 and ORF125 appeared to be suitable markers to study regional spread of WSSV.

Animals↗
PubMed2002

Systemic lupus erythematosus in three ethnic groups. X. Measuring cognitive impairment with the cognitive symptoms inventory.

OBJECTIVE: To determine the factor structure of the Cognitive Symptoms Inventory (CSI) in patients with systemic lupus erythematosus (SLE) participating in a multiethnic longitudinal study of outcome, the Lupus in Minority populations, Nature versus nurture (LUMINA) study. METHODS: LUMINA patients of Hispanic (n = 48), African American (n = 64), and Caucasian (n = 44) ethnicity who had a study visit (enrollment or followup) between January 1 and September 30, 2000 were included. Patients completed the CSI, a 21-item self-report measure of cognitive function. Sociodemographic, clinical, immunologic, psychosocial, and behavioral variables were ascertained per protocol and as previously described. Data were analyzed with SPSS. The factor structure of the CSI was determined using the principal axis method with oblique rotation as decided by Gorsuch. All factors having an Eigenvalue greater than 1 were considered. A 4-factor solution was derived that accounted for 42.6% of the common variance. The correlations between patient factor scale scores and variables from the demographic, clinical, psychosocial, and behavioral domains were then examined. RESULTS: The four factors and their respective variance are, Attention/Concentration (28.8%), Pattern Recognition/Activity Management (5.7%), Intermediate Memory (4.7%), and Initiation of Executive Functions (3.4%); each factor correlated with the total CSI score. Overall, patients' factor scale scores were positively and significantly correlated with other measures of cognitive dysfunction such as the Systemic Lupus Activity Measure (neuromotor domain) or the Systemic Lupus International Collaborating Clinics Damage Index (neurocognitive impairment), as well as with measures of fatigue, maladaptive coping skills, poor mental functioning, poor social support, and helplessness. They were, however, not correlated with sociodemographic or clinical variables. CONCLUSIONS: In addition to demonstrating that the CSI can be used to measure cognitive impairment in patients with SLE in the research setting, we have determined a 4-factor solution for the CSI that appears to have adequate metric properties. At present, the CSI may best be used as a screen for difficulties in daily activities involving intermediate memory, concentration, attention, and executive function. Nevertheless, further work with the CSI items and factor scales is necessary to establish internal and test-retest reliability of the factor scales; and provide additional evidence of the convergent and predictive validity of these scales in larger samples of patients from each ethnic subgroup.

Adult↗
PubMed1996

Variability in gene expression and tumor formation within genetically homogeneous animal populations in bioassays.

Considerable variation in susceptibility to tissue-specific tumor formation in response to chronic treatment with low or intermediate dose levels of putative carcinogens is observed within populations of genetically homogeneous test animals under controlled environmental conditions. Experimental evidence from National Toxicology Program studies is reviewed, as are studies of differing degrees of carcinogenic response and tumor promotion among iso-and congenic mice carrying the Avy (viable yellow) mutation. The data suggest that individual variations in carcinogenic response among genetically homogeneous animals may derive primarily from differences in regulation of gene transcription. Differences in posttranscriptional and posttranslational processing of gene products are probably also contributing factors. The viable yellow Avy/a mouse model system is uniquely suited for investigating the developmental and molecular bases of this phenotypic variability in genetically homogeneous populations since various degrees of carcinogenic response and promotion of tumor formation can be predicted, a priori, at least as early as 7 days of age by correlation with coat color patterns. Ectopic expression of the agouti protein results in enhanced susceptibility to tumor formation in tissues which are already sensitized to neoplastic transformation by their strain genome. The differences in tumorigenic response and coat color pattern among Avy/- mice appear to be associated with different DNA methylation states of the promoter of an intracisternal A particle inserted into exon 1A of the agouti gene.

Animals↗
PubMed2001

Noise-induced transition in excitable neuron models.

We studied the influence of noisy stimulation on the Hodgkin-Huxley neuron model. Rather than examining the noise-related variability of the discharge times of the model--as has been done previously--our study focused on the effect of noise on the stationary distributions of the membrane potential and gating variables of the model. We observed that a gradual increase in the noise intensity did not result in a gradual change of the distributions. Instead, we could identify a critical intermediate noise range in which the shapes of the distributions underwent a drastic qualitative change. Namely, they moved from narrow unimodal Gaussian-like shapes associated with low noise intensities to ones that spread widely at large noise intensities. In particular, for the membrane potential and the sodium activation variable, the distributions changed from unimodal to bimodal. Thus, our investigation revealed a noise-induced transition in the Hodgkin-Huxley model. In order to further characterize this phenomenon, we considered a reduced one-dimensional model of an excitable system, namely the active rotator. For this model, our analysis indicated that the noise-induced transition is associated with a deterministic bifurcation of approximate equations governing the dynamics of the mean and variance of the state variable. Finally, we shed light on the possible functional importance of this noise-induced transition in neuronal coding by determining its effect on the spike timing precision in models of neuronal ensembles.

Action Potentials↗
PubMed2003

Hepatitis C virus E2 and NS5A region variability during sequential treatment with two interferon-alpha preparations.

To determine the pattern and significance of the HCV genetic heterogeneity before and during treatment with recombinant-2b or lymphoblastoid alpha-interferon, hypervariable region 1 (HVR-1) and NS5A quasispecies were characterised by cloning and sequencing in 12 HCV-1b-infected subjects. Patients were either responder-relapsers or non-responders to treatment. Extensive amino acid sequence analysis was applied to reveal the significance of HCV variation at key sites within HVR-1 and NS5A regions. Genetic complexity, genetic diversity, and the non-synonymous to synonymous substitution ratios of HVR-1 quasispecies decreased during treatment in responder-relapser patients only, and more markedly so following lymphoblastoid alpha-interferon. In non-responders, the HVR-1 quasispecies broadened. Amino acids G406 and Q409, which represent a major viral epitope, were highly conserved throughout treatment. Responder-relapser patients had a higher mutation frequency in NS5A than non-responders. Lymphoblastoid alpha-interferon promoted the selection of intermediate Interferon Sensitivity Determining Region (ISDR) sequences, whereas recombinant-2b alpha-interferon favoured maintenance or selection of conserved ISDR sequences. Variability upstream of the ISDR was associated with treatment response, but the amino acid substitutions conferring higher replicative ability to in vitro HCV replicons were absent in in vivo isolates. In conclusion, the pattern of HVR-1 quasispecies evolution correlates with the clinical response, and the conservation of specific amino acids may be useful for immune targeting in vivo. In responder-relapser patients, the initial HVR-1 evolution resembles that found in sustained responders. Variability within the entire NS5A, as opposed to a single region (ISDR), may have a role in influencing alpha-interferon treatment outcome. A differential effect of different alpha-interferon preparations on HCV quasispecies kinetics may exist.

Amino Acid Sequence↗
PubMed2006

Comparison of exercise echocardiography and the Duke treadmill score for risk stratification in patients with known or suspected coronary artery disease and normal resting electrocardiogram.

BACKGROUND: Although exercise echocardiography (EE) is not clearly indicated in patients with normal electrocardiogram (ECG) as the first evaluation, there is a lack of data regarding its superiority over the Duke score for prognosis. We investigate whether EE has incremental value over the Duke score for predicting outcome in patients with normal ECG. METHODS: One thousand six hundred forty-seven patients with interpretable ECG referred for EE were followed up for 2.5 +/- 1.4 years. There were 58 hard events (myocardial infarction or cardiovascular death). RESULTS: There were 38 events in 735 patients with abnormal EE versus 20 events in 912 with normal EE (P < .0001). The Duke score, resting wall motion score index, and ischemia were independently associated to events (incremental P value of EE = .03). The Duke score allowed stratification of patients with abnormal EE (P = .001) or ischemia (P = .01) into different risk categories but did not stratify patients without these characteristics. Exercise echocardiography variables stratified patients with the low Duke score (left anterior descending artery territory P = .04, left anterior descending artery ischemia P = .03) and with the intermediate Duke score (abnormal EE P = .005, necrosis P = .0009, ischemia P = .004, resting ejection fraction P < .00001, resting wall motion score index P < .00001, peak ejection fraction P < .00001, peak wall motion score index P < .0001, number of territories P = .002, left anterior descending artery territory P = .001, and left anterior descending artery ischemia P = .002) but did not with the high Duke score. CONCLUSIONS: Exercise echocardiography has incremental value over clinical variables, the Duke score, and resting echocardiography for the prediction of hard cardiovascular events in patients with normal resting ECG.

Coronary Artery Disease↗
PubMed2003

Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients.

Three genes commonly causing Charcot-Marie-Tooth disease (CMT) encode myelin-related proteins: peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32). Demyelinating versus axonal phenotypes are major issues in CMT associated with mutations of these genes. We electrophysiologically, pathologically and genetically evaluated demyelinating and axonal features of 205 Japanese patients with PMP22 duplication, MPZ mutations or Cx32 mutations. PMP22 duplication caused mainly demyelinating phenotypes with slowed motor nerve conduction velocity (MCV) and demyelinating histopathology, while axonal features were variably present. Two distinctive phenotypic subgroups were present in patients with MPZ mutations: one showed preserved MCV and exclusively axonal pathological features, while the other was exclusively demyelinating. These axonal and demyelinating phenotypes were well concordant among siblings in individual families, and MPZ mutations did not overlap among these two subgroups, suggesting that the nature and position of the MPZ mutations mainly determine the axonal and demyelinating phenotypes. Patients with Cx32 mutations showed intermediate slowing of MCV, predominantly axonal features and relatively mild demyelinating pathology. These axonal and demyelinating features were present concomitantly in individual patients to a variable extent. The relative severity of axonal and demyelinating features was not associated with particular Cx32 mutations. Median nerve MCV and overall histopathological phenotype changed little with disease advancement. Axonal features of diminished amplitudes of compound muscle action potentials (CMAPs), axonal loss, axonal sprouting and neuropathic muscle wasting all changed as disease advanced, especially in PMP22 duplication and Cx32 mutations. Median nerve MCVs were well maintained independently of age, disease duration and the severity of clinical and pathological abnormalities, confirming that median nerve MCV is an excellent marker for the genetically determined neuropathic phenotypes. Amplitude of CMAPs was correlated significantly with distal muscle strength in PMP22 duplication, MPZ mutations and Cx32 mutations, while MCV slowing was not, indicating that clinical weakness results from reduced numbers of functional large axons, not from demyelination. Thus, the three major myelin-related protein mutations induced varied degrees of axonal and demyelinating phenotypic features according to the specific gene mutation as well as the stage of disease advancement, while clinically evident muscle wasting was attributable to loss of functioning large axons.

Action Potentials↗
PubMed2004

Effect of supplemental tryptophan, vitamin E, and a herbal product on responses by pigs to vibration.

Economic losses related to increased stress during the transport of pigs are well documented. The effects of supplementing of tryptophan (Trp), vitamin E, or a herbal product via feed or drinking water were investigated in terms of effects on stress response in pigs during transport simulation. The study consisted of three analogous experiments. For the testing in each experiment, the pigs (23.5+/-3.2 kg) were allocated to one of two treatments, with and without supplementation of a product. The applied doses were Trp (5 g/L drinking water for 3 d), vitamin E (additional amount of 300 mg/kg feed for 21 d, as-fed basis), and Sedafit (2.5 g/L drinking water for 2 d). Sedafit is a commercial herbal product containing Valeriana officinalis L. and Passiflora incarnata L. as active components. In each experiment of the study, at least 47 pigs were involved, which were treated in groups of 3. The day before transport simulation, a Holter device was attached to the pigs to produce an electrocardiogram during the night (rest values), as well as during vibration in the transport simulator (1.2 Hz, 1 m/s2), where the behavior of the pigs (standing-sitting-lying) was also observed. Samples of saliva (taken before, during, and after [3x] vibration) and blood (taken before and after vibration) were analyzed for cortisol and intermediate metabolites (glucose, lactate, creatine kinase, and nonesterified fatty acids), respectively. Pigs supplemented with Trp tended to spend more time lying down during the second hour of vibration (P < 0.05). Vitamin E decreased the peak heart rate (P < 0.05), ventricular ectopic beats (P < 0.01), and ST elevation (P < 0.10). The supplementation of Sedafit resulted in smaller increases of the investigated heart variables (minimum heart rate, P < 0.05; ventricular ectopic beats, P < 0.05; ST elevation, P < 0.01) during and after stress evocation compared with the control group. None of the tested products influenced the intermediate metabolites; one possible explanation for this finding may be that peak values were reached before the time of bleeding. In conclusion, Trp had a positive behavioral effect in this experiment, and vitamin E and Sedafit mediated an increase in some heart variables, suggesting sedative and antianxiety effects.

Animals↗
PubMed1992

Reactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro.

We hypothesized that muscle fiber bundles produce reactive oxygen intermediates and that reactive oxidant species contribute to muscular fatigue in vitro. Fiber bundles from rat diaphragm were mounted in chambers containing Krebs-Ringer solution. In studies of intracellular oxidant kinetics, bundles were loaded with 2',7'-dichlorofluorescin, a fluorochrome that emits at 520 nm when oxidized; emissions were quantified using a fluorescence microscope. Emissions from unstimulated muscles increased over time (P < 0.001). Accumulation of fluorescence was slowed by addition of catalase (P < 0.001) or superoxide dismutase (P < 0.001) and was accelerated by repetitive muscular contraction (P < 0.05). To determine effects of reactive oxygen intermediates on fatigue, curarized bundles were stimulated to contract isometrically; force was measured. Catalase, superoxide dismutase, and dimethyl sulfoxide were screened for effects on low- and high-frequency fatigue. Antioxidants inhibited low-frequency fatigue [after 5 min of repetitive contractions, force at 30 Hz was 20% greater than control (P < 0.015)] and increased the variability of fatigue at 30 Hz (P < 0.03). Antioxidants did not alter high-frequency (200-Hz) fatigue. We conclude that 1) diaphragm fiber bundles produce reactive oxygen intermediates, including O2-. and H2O2; 2) muscular contraction increases intracellular oxidant levels; and 3) reactive oxygen intermediates promote low-frequency fatigue in this preparation.

Animals↗
PubMed2005

Variable incidence of cyclosporine and FK-506 neurotoxicity in hematopoeitic malignancies and marrow conditions after allogeneic bone marrow transplantation.

INTRODUCTION: This study examines whether malignant disease under treatment influences the incidence of cyclosporine or FK-506 neurotoxicity after myeloablative conditioning and allogeneic bone marrow transplantation (allo-BMT). METHODS: Review of 290 patients who received myeloablative conditioning prior to allo-BMT and cyclosporine/FK-506 identified 21 (7.2%) patients with neurotoxicity confirmed by computed tomography or magnetic resonance. Underlying malignancy necessitating allo-BMT included leukemias (67%), lymphoma (10%), myelodysplastic syndrome (10%), and multiple myeloma (MM). Frequency of neurotoxicity by disease was compared. RESULTS: The highest incidence of neurotoxicity was present with MM (25%), whereas the lowest incidence was present with lymphoma (2.7%). Other diseases demonstrated intermediate incidence, including acute leukemias (10%), myelodysplastic syndrome (6.4%), and chronic myelogenous leukemia (4.9%). CONCLUSION: Cyclosporine/FK-506 neurotoxicity varied according to the underlying malignancy. The variable susceptibility to the development of neurotoxicity in this population may depend on the interaction of host vasculature with disease specific factors. Understanding the cause of neurotoxicity could improve survival after allo-BMT.

Bone Marrow Transplantation↗
PubMed1982

The cytoskeleton in tumor cells.

During the past few years several laboratories investigated the occurrence of cytoskeletal components in epithelial and mesenchymal cells by electron microscopy and/or immunocytochemical methods in a number of tumor types growing in vitro or in the body. Since it is well established that antibodies to different intermediate-sized filament proteins can distinguish cells and tissues of epithelial, mesenchymal, muscle, astrocytic and neural origin special attention has been paid to the behaviour of these filaments in neoplastic cells recently. While the organisation of the cytoskeleton in tumor cells growing in vitro is very variable, regularities relevant for the diagnosis and the determination of the histogenetic origin of tumors have been observed in tumor cells growing in the body. In general, ultrastructural and immunological features of intermediate filaments are maintained during neoplastic transformation in the body. Thus immunofluorescence microscopy with antibodies to cytoskeletal proteins is a powerful tool for the classification and differential diagnosis of tumors, especially for the distinction between epithelial and mesenchymal tumors, including metastases. The concept that presence of an excess of contractile proteins such as actin is an important prerequisite for the metastatic spread of malignant cells has not been unequivocally supported by more recent results. However, an accumulation of various types of intermediate filaments (e.g. prekeratin, vimentin, acidic glial fibrillar protein) has been shown in different tumor types. The further elucidation of this alteration could contribute to a better understanding of the molecular mechanisms of neoplastic cell transformation.

Adenoma, Bile Duct↗
PubMed2000

Combined analyses of RAPDs, cpDNA and morphology demonstrate spontaneous hybridization in the plant genus Chaenomeles.

Evidence of spontaneous hybridization between two partially sympatric species of Chaenomeles, C. cathayensis and C. speciosa, has been obtained through analysis of offspring families from these two species, as well as from two presumed interspecific hybrid populations. A combination of different methods was applied. Analysis of diagnostic RAPD markers and of chloroplast DNA haplotypes supported the notion of spontaneous hybridization, and suggested that there has been symmetrical, rather than unidirectional, introgression between C. cathayensis and C. speciosa. RAPDs and morphological characters revealed concordant patterns of genetic relatedness among the studied offspring families. Some putative hybrid families had mainly intermediate characters, whereas others appeared to be later generation hybrids as they were genetically and phenotypically rather similar to families that appeared to represent pure species. The RAPD-based proportion of between-family variability was considerably higher in the putatively hybridogenous populations than in populations of the pure species. Within-family gene diversity estimates ranged from C. speciosa (max. Hj = 0.235) to C. cathayensis (min. Hj = 0.094) with the presumed hybrid families taking intermediate values.

Chloroplasts↗
PubMed2004

Effect of partial and complete variable loop deletions of the human immunodeficiency virus type 1 envelope glycoprotein on the breadth of gp160-specific immune responses.

Induction of cross-reactive cellular and humoral responses to the HIV-1 envelope (env) glycoprotein was examined after DNA immunization of BALB/c mice with gp140(89.6)-derived constructs exhibiting partial or complete deletions of the V1, V2, and V3 domains. It was demonstrated that specific modification of the V3 loop (mV3) in combination with the V2-modified (mV2) or V1/V2-deleted (DeltaV1/V2) region elicited increased levels of cross-reactive CD8(+) T cell responses. Mice immunized with the mV2/mV3 or DeltaV1/V2/mV3 gp140(89.6) plasmid DNA were greater than 50-fold more resistant to challenge with recombinant vaccinia virus (rVV) expressing heterologous env gene products than animals immunized with the wild-type (WT) counterpart. Sera from mV2/mV3- and DeltaV1/V2/mV3-immunized mice exhibited the highest cross-neutralizing activity and displayed intermediate antibody avidity values which were further enhanced by challenge with rVV expressing the homologous gp160 glycoprotein. In contrast, complete deletion of the variable regions had little or no effect on the cross-reactive antibody responses. The results of these experiments indicate that the breadth of antibody responses to the HIV-1 env glycoprotein may not be increased by removal of the variable domains. Instead, partial deletions within these regions may redirect specific responses toward conserved epitopes and facilitate approaches for boosting cross-reactive cellular and antibody responses to the env glycoprotein.

Amino Acid Sequence↗
PubMed1991

Persistence of an embryonic intermediate filament-associated protein in the smooth muscle cells of elastic arteries and in Purkinje fibres.

During differentiation of most myogenic tissues, vimentin is transiently expressed as the intermediate filament (IF) protein subunit and is progressively replaced by desmin. However, smooth muscle cells of mature vascular tissue contain variable amounts of vimentin whose cellular content decreases as function of the distance from the heart. IFAPa-400 is a developmentally regulated IF crosslinker protein whose expression appears to parallel that of vimentin during chick myogenesis. Immunohistological and immunoblot techniques were employed to study the expression of this protein in cardiac and vascular smooth muscle cells of the adult chicken. As observed for vimentin, the expression of IFAPa-400 persists in the mature smooth muscle cells of the large arteries as they leave the heart. However, both of these proteins are down-regulated according to a proximo-distal gradient with respect to the distance from the heart. Conversely, desmin is much more abundant in the distal segments of the aorta. Thus, the co-ordinate expression of vimentin with IFAPa-400 may be a characteristic feature of elastic vascular tissue in which it could meet mechanical requirements close to those of the embryonic cells expressing them. This hypothesis is supported by the observation that the single cell type which continues to express the vimentin-IFAPa-400 combination in the mature heart is the Purkinje fibres, which are also subjected to high mechanical tensions but in which myofibrils are generally sparse compared to working myocytes.

Aging↗
PubMed1999

Reactive oxygen intermediate production by oyster hemocytes exposed to hypoxia

Oysters are frequently exposed to severely hypoxic conditions, especially during summer months. During the summer, there are also large numbers of disease-related oyster mortalities. This research was conducted to determine whether exposure to environmental hypoxia reduces the ability of oyster hemocytes to produce reactive oxygen intermediates (ROIs), an important part of their defense system. Oysters of the species Crassostrea virginica were held in normoxic (P(O)(2)=20.0-20.7 kPa, pH 7.8-8.0) and hypoxic conditions (P(O)(2)=4.0-6.7 kPa, pH 7.1-7.4). In vivo hemolymph variables (P(O)(2), P(CO)(2) and pH) were measured after both 1 hour and 2 days in each treatment to determine the appropriate environment for subsequent hemocyte experiments. Production of reactive oxygen intermediates by hemocytes was measured using luminol-enhanced chemiluminescence (CL). During CL tests, hemocytes were held under the following conditions: air (P(O)(2)=20.7, P(CO)(2)<0.07, pH 7.6), in vivo hemolymph conditions of normoxic oysters (P(O)(2)=5.2, P(CO)(2)=0.27, pH 7.6), and in vivo hemolymph conditions of hypoxic oysters (P(O)(2)=1.47, P(CO)(2)=0.53, pH 7.1). Production of ROIs under hypoxic conditions was 33 % of that under normoxia. This decrease was the result of specific and independent effects of lower oxygen levels and decreased pH. It was not due to any direct effect of CO(2).

Journal Article↗
PubMed1990

Intermediate filament proteins and actin isoforms as markers for soft-tissue tumor differentiation and origin. III. Hemangiopericytomas and glomus tumors.

Intermediate filament proteins and actin isoforms of a series of 12 malignant hemangiopericytomas and five glomus tumors were examined by light microscopy, transmission electron microscopy, two-dimensional gel electrophoresis (2D-GE), and by immunohistochemistry, the latter using monoclonal or affinity-purified polyclonal antibodies to desmin, vimentin, cytokeratins, alpha-smooth muscle, and alpha-sarcomeric actins. By light microscopy, all hemangiopericytomas disclosed a predominant vascular pattern with scant storiform, myxoid and spindle cell areas, and with variable degrees of perivascular fibrosis. By ultrastructure, smooth muscle differentiation was observed in each hemangiopericytoma. Immunohistochemically, neoplastic cells of hemangiopericytomas expressed vimentin as the sole intermediate filament protein and lacked alpha-smooth muscle or alpha-sarcomeric actins. 2D-GE revealed only beta and gamma actins, in proportions typical for fibroblastic tissues. Glomus tumors revealed vimentin and alpha-smooth muscle actin within glomus cells by immunohistochemical techniques and disclosed ultrastructurally distinct smooth muscle differentiation. Therefore hemangiopericytomas represent a distinct soft-tissue neoplasm with uniform morphologic, immunohistochemical, and biochemical features most likely related to glomus tumors, the former representing an aggressive and potentially malignant neoplasm of vascular smooth muscle cells and the latter a well-differentiated neoplasm of vascular smooth muscle cells. Because malignant hemangiopericytomas disclose smooth muscle differentiation by ultrastructure, but do not express alpha-smooth muscle actin, as normal pericytes and glomus cells, it is suggested that these neoplasms represent highly vascularized smooth muscle neoplasms, ie, poorly differentiated leiomyosarcomas derived from vascular smooth muscle cells or their equivalent, the pericytes, which have lost alpha-smooth muscle actin as a differentiation marker that is similar to many conventional poorly differentiated leiomyosarcomas.

Actins↗