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[Cervical lymph node surgery in differentiated thyroid cancer: selective or elective lymphadenectomy?].

The value and prognostic significance of regional lymph node dissection in patients with thyroid cancer remains a matter of controversy. The classification of the cervical lymph nodes and the extent of their resection in patients with different thyroid cancers is also discussed. The aim of the paper was to present the space classification of regional lymph nodes, the incidence of their involvement and the extent of their resection in patients with differentiated thyroid cancer. The results of multicenter studies have indicated that regional lymph node metastases in patients with differentiated thyroid cancer, especially of a papillary type, have been frequent. Ipsilateral central, ipsilateral lateral, contralateral lateral, and mediastinal lymph nodes have been affected in 42-86%, 32-68%, 12-24%, and 3-20% of patients respectively. In 20% of patients only central lymph nodes have been affected, whereas in others metastases have been determined at least in 2 or more lymph node groups. Regional lymph nodes have been classified into Groups I-IV. Moreover, lymph node recurrences have been more frequent in patients who either have not got the regional lymph nodes removed or have only enlarged ones determined as involved excised. Therefore, primary regional lymph nodes dissection is indicated. Elective resection of the lymph nodes of Group I (central lymph nodes) as a part of primary total thyroidectomy in patients with thyroid cancer and more selective excision of the lymph nodes of Groups II-IV are recommended. The author has presented his own experience in lymph node dissection in patients with differentiated thyroid cancer and compared it with other results.

Humans↗

Ethanol-induced grooming in mice selectively bred for differential sensitivity to ethanol.

In rats, excessive grooming follows the application of several forms of stress. The injection of alcohol may be considered as a stressor, since it increases plasma corticosterone levels. The present study examines the effects of ethanol injections on grooming in two lines of mice selected for differences in their hypnotic response to ethanol, i.e., the long sleep (LS) and short sleep (SS) lines developed at the Institute for Behavior Genetics at the University of Colorado at Boulder. Various subhypnotic doses of ethanol produced excessive grooming in the SS line, but this did not occur in the LS line. The SS mice also displayed more "novelty-induced" grooming compared to the LS mice after repeated exposure to the testing situation. The increase in excessive grooming in both the ethanol-induced and the novelty-induced excessive grooming situations was most apparent in the second half of the observation period.

Animals↗

[Indications for the use of differential ventilation and selective positive end-expiratory pressure].

In some cases of unilateral or bilateral severe lung disease, there is serious hypoxia despite a high level of oxygen in the inspiratory gas mixture. Disturbances in the ventilation/perfusion ratio (V/Q) is a major contributing factor to the hypoxia seen in acute lung disease. The use of positive end expiratory pressure (PEEP) has in some cases been shown to make this V/Q mismatch even worse, and the use of high levels of PEEP is known to increase the risk of barotrauma and to reduce cardiac output. In this article, a method is described which makes it possible to ventilate each lung separately in proportion to its expected perfusion (differential lung ventilation), with or without the use of PEEP to one or both lungs (selective PEEP). Because of a more uniform V/Q the oxygenation in unilateral as well as in bilateral lung disease is improved. The risk of barotrauma as well as the impact on cardiac output is reduced. The patient has to be intubated with a double lumen endotracheal catheter. The gas is delivered by two ventilators synchronized by a master-slave cable. This method can also be used in the operating room, when surgical procedures have to take place in the lateral position, in order to counteract V/Q mismatch and hypoxia.

Humans↗

Selective serotonin1A/1B agonists differentially affect spinal nociceptive reflexes.

The purpose of the present experiments was to determine whether serotonin-1A (5-HT1A) and serotonin-1B (5-HT1B) binding sites, recently characterized in the spinal cord of the rat, mediate differential effects of 5-HT on spinal nociceptive processing. Several days after spinal transection at T10, rats were injected intraperitoneally at 20 min intervals, with increasing doses (0, 0.1, 0.4, 2.0, 9.0 mg/kg) of either a 5-HT1A selective agonist (8-OH-DPAT, buspirone) or a 5-HT1B agonist (mCPP, TFMPP). Nociceptive sensitivity was determined by quantifying, in cm2, changes from baseline in the receptive field areas of three spinal nociceptive withdrawal reflexes after noxious (greater than 400 mmHg) levels of mechanical stimulation. The 5-HT1A agonist 8-OH-DPAT and buspirone, significantly increased in a dose-dependent manner the receptive field areas of the three reflexes, with the following log ED50 values (nmol/kg): ventroflexion reflex--buspirone (2.75), 8-OH-DPAT (2.70); dorsiflexion reflex--buspirone (2.91), 8-OH-DPAT (2.67); lateral flexion reflex--buspirone (3.51), 8-OH-DPAT (2.77). The hypersensitivity of the reflexes after pretreatment with buspirone was effectively blocked by the 5-HT1A selective antagonist spiperone, at all doses (0.001, 0.01, 0.1 and 1.0 mg/kg) tested. The 5-HT1B selective agonists mCPP and TFMPP significantly decreased the receptive field are of the ventroflexion reflex (log ED50 values: mCPP, 3.79 nmol/kg; TFMPP, 3.61 nmol/kg) with no significant effect on the dorsiflexion or lateral flexion reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Myocardial alpha 1A-adrenoceptor subtypes in rabbit: differentiation by a selective antagonist, HV723.

The influence of a newly developed alpha 1-adrenoceptor antagonist, HV723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxy-phenoxy)ethyl)-ami no)- propyl) benzeneacetonitrile fumarate), on the positive inotropic effect and acceleration of phosphoinositide hydrolysis induced by phenylephrine via alpha 1-adrenoceptors in the presence of bupranolol (0.3 microM) was studied in the rabbit ventricular muscle: (1) HV723 at low concentrations (1-100 pM) attenuated the maximal inotropic response by 15-20% without altering the pD2 value for and [3H]inositol monophosphate accumulation induced by phenylephrine. The inhibitory action of HV723 (1-100 pM) showed a close resemblance to that of a selective alpha 1A antagonist, (+)-niguldipine. (2) HV723 (> or = 1 nM) shifted the concentration-response curve for phenylephrine to the right and downwards in association with a partial inhibition (42.5%) of [3H]inositol monophosphate accumulation. The IC50 values of HV723 for the inhibition of the inotropic response and phosphoinositide hydrolysis were approximately equal to the Kilow value determined by displacement of [3H]prazosin-specific binding. The mode of the inhibitory action of HV723 (> or = 1 nM) resembled that of another alpha 1A antagonist, WB 4101. These results indicate that HV723 shows a differential antagonistic action on the alpha 1A-mediated responses depending on the concentration: HV723 (1-100 pM) selectively inhibits the (+)-niguldipine-sensitive subclass to lead to a decrease in the maximal inotropic response with no change in phosphoinositide hydrolysis; HV723 (> or = 1 nM) may antagonize the WB 4101-sensitive subtype coupled to acceleration of phosphoinositide hydrolysis.

Acetonitriles↗

Responses to cholinergic agonists of rats selectively bred for differential sensitivity to ethanol.

Alcoholics are almost invariably heavy users of tobacco. Both alcoholism and smoking appear to be influenced by genetic factors but it is not known whether the same or different genes regulate the abuse of ethanol and nicotine. Recent studies have demonstrated that the long-sleep (LS) and short-sleep (SS) mouse lines, which were selectively bred for differences in ethanol-induced anesthesia ("sleep-time"), also differ in several effects of nicotine and the muscarinic agonist, oxotremorine. In order to determine whether or not these differences are due to chance, the relative sensitivities of rat lines which were selectively bred for differences in ethanol-induced sleep-time were determined. The high alcohol sensitivity (HAS) rat line was more sensitive to the locomotor and body temperature depressant effects of nicotine than was the low alcohol sensitivity (LAS) rat line. The control line (CAS) was intermediate in sensitivity. The rat lines did not differ in sensitivity to oxotremorine's hypothermia-producing effects. The numbers and affinities of two classes of brain nicotinic receptors were measured in eight brain regions. No differences among the rat lines were detected. These results suggest that ethanol elicits some of its depressant actions via an effect on brain nicotinic systems, but the differences in sensitivity to ethanol and nicotine are probably not due to differences in the number of brain nicotinic receptors. Perhaps this interaction explains the high correlation between alcoholism and smoking in humans.

Animals↗

Both intrathymic and peripheral selection modulate the differential expression of V beta 5 among CD4+ and CD8+ T cells.

Murine T cells expressing V beta 5 are characterized by (a) intrathymic deletion in the presence of I-E and products of endogenous mouse mammary tumor viruses, and (b) a greater representation in CD8+ relative to CD4+ peripheral T cells, thought to be due to more efficient intrathymic positive selection on class I rather than class II major histocompatibility complex antigens. We have engineered mice that are transgenic for a rearranged gene encoding a V beta 5+ beta chain of the T cell receptor for antigen. Deletion is not predicted in I-E- V beta 5+ transgenic mice, and until the age of 2 wk, the CD4/CD8 ratio of peripheral T cells is > 3:1 and indistinguishable between transgenic and nontransgenic mice. Transgenic mice then show a rapid, age-dependent decline in the ratio of CD4+ to CD8+ T cells in the lymphoid periphery, reaching a low of 1:10 by 7 mo of age. Furthermore, the percent of peripheral CD4+ cells that express the transgene drops with age, reaching a low of about 60% at 7 mo, while the percent of CD8+ cells that express V beta 5 remains greater than 95% at all ages. The lymphoid periphery is implicated in this selection against CD4+ V beta 5+ T cells as it occurs more rapidly in thymectomized transgenic mice, and can be delayed in mice whose peripheral T cells are replaced by recent thymic emigrants after depletion by in vivo treatment with anti-Thy-1 antibodies. These results indicate that the relative expression of V beta 5 in T cell subsets can be influenced not only intrathymically in I-E+ V beta 5+ transgenic mice, but also by events in the periphery, in the absence of I-E expression.

Animals↗

Selective detection and differentiation of subgenus B adenoviruses (types 3, 7 and 11) by polymerase chain reaction.

Application of the polymerase chain reaction (PCR) method for detection of subgenus B adenoviruses (types 3, 7 and 11) was investigated. It is based on a simple (nonnested) PCR using primer pairs specific for the hexon-coding region. The PCR allowed amplification of DNA from subgenus B adenovirus prototype strains (types 3, 7 and 11) and adenovirus isolates (types 3 and 7), whereas it did not amplify DNA from subgenus A (type 31), C (types 1, 2, 5 and 6), D (types 8, 19 and 37), E (type 4) and adenovirus isolates (types 1, 2, 5 and 6). These results suggest that subgenus B adenoviruses (types 3, 7 and 11) are detectable selectively by means of PCR with primer pairs developed in this study. Amplified fragments from adenovirus types 3, 7 and 11 could be differentiated with restriction endonuclease analysis with Rsa I.

Adenoviridae↗

Operant rate depressant effects of ethanol in mice selectively bred for differential neurosensitivity to ethanol.

Few studies have investigated genetic differences in the effects of ethanol on operant schedule-controlled behaviors. The use of genetically defined populations in sensitive measures of complex behavior can help determine genetically covarying responses to ethanol as well as environmental contexts important for demonstrating genetic differences. The purpose of the present study was to investigate the rate depressant effects of ethanol on two lines of mice selectively bred for increased, LS/Ibg (LS), and decreased, SS/Ibg (SS), sensitivity to the acute narcotic effects of ethanol. Ethanol dose-dependently decreased high rates of behavior maintained by fixed ratio responding for water in both the LS and SS mice. Interestingly, the LS and SS mice did not differ in the rate depressant effects of ethanol under these conditions despite the sensitivity of this measure to the CNS effects of drugs and the very large differences between these lines in sensitivity to numerous other ethanol-related effects. While the SS mice were slightly less sensitive, and LS mice tended to show a low dose rate increasing effect, none of the differences were significant as ED50 values for rate depression differed by only 2.5 percent. The results of this experiment demonstrate that sensitivity to the effects of ethanol on fixed ratio responding for water is not genetically related to the acute narcotic effects of ethanol. In addition, the findings show that previously reported differences in operant ethanol self-administration between these two lines of mice are not due to differential sensitivity to the direct effects of ethanol on reinforced behavior.

Animals↗

Selective sexual harassment: differential treatment of similar groups of women workers.

If male workers categorize different groups of women coworkers and, subsequently, treat them differently, the experiences of women from one of these groups would not be indicative of the experiences of women from another group. When this different treatment involves hostile environment sexual harassment of one group, but not the other, then the law must recognize the possibility of "selective sexual harassment." Without this understanding of the nuances of the workplace dynamics, a court could mistake the women of the unharassed group as representing "reasonable women" and the women of the harassed group as simply oversensitive. This paper draws on empirical data to demonstrate such a situation and advocates for a version of the "reasonable victim" standard to facilitate a closer analysis of hostile environment sexual harassment suits.

Data Collection↗

Profiling and selection of genes differentially expressed in the pylorus of rat strains with different proliferative responses and stomach cancer susceptibility.

Rat stomach cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are widely used as a model of differentiated-type human stomach cancers. ACI/NJcl (ACI) rats show persistent and strong cell proliferation in response to gastric mucosal damage by MNNG while BUF/NacJcl (BUF) rats show transient and limited cell proliferation. This difference is considered as one of the mechanisms for the high susceptibility of ACI rats to MNNG-induced stomach carcinogenesis. To identify genes involved in the differential induction of cell proliferation, cDNA subtraction was performed using RNA isolated from the pylorus of ACI and BUF rats treated with MNNG. By the temporal patterns of their expressions, the isolated 16 genes were overviewed and clustered into groups. Expression of the genes in group 1 (such as MHC class I and class II genes and interferon-inducible genes Iigp, Mx2 and Ubd) was induced by MNNG treatment, and the genes in group 2 (such as cellular retinoic acid-binding protein II (CrabpII)) were constantly expressed regardless of MNNG treatment. Then, expression profiles among multiple rat strains were compared with the extents of induction of cell proliferation. Iigp, CrabpII and EST222005 were found to show relatively good accordance, and these three genes were considered as candidates for genes that control differential induction of cell proliferation. Presence of polymorphisms at the genomic DNA level was indicated for CrabpII and EST222005, and these two genes were considered to be better candidates than IIGP: It was shown that the temporal profiles and profiles among strains, taking advantage of animal models, are useful to select candidate genes from a collection of genes isolated by various genome-wide scanning methods.

Animals↗

Natural selection and genetic differentiation of behaviour between parasitoids from wild and cultivated habitats

Differences in behaviour between individuals in populations living in different environments may result from evolution proceeding differently in each population. The parasitoid wasp Cotesia glomerata (L.) (Hymenoptera: Braconidae) parasitizes early instar larvae of butterflies in the family Pieridae. In the study area the only host of C. glomerata is the Small Cabbage White Butterfly [Pieris rapae (L.) (Lepidoptera: Pieridae)], which feeds on cruciferous host plants in a variety of habitats. The behaviour of this parasitoid wasp collected from two habitat types (wild and agricultural) was observed in a reciprocal transplant-style experiment in a greenhouse. Differences in behaviour between wasp sources and test habitat type were analysed using canonical analysis in multivariate analysis of variance. Directional selection on parasitoid behaviour in each test habitat type was estimated by regressing the relative rate of parasitism (a measure of relative fitness) on the behavioural character state. We found that there is genetic differentiation of behaviour between wasps from wild and cultivated habitats and that a different set of behaviours is associated with short-term fitness within models of each source habitat. There was no evidence of local adaptation of wasps to either habitat.

Journal Article↗

Selective stimulation and differentiation of early antigens in lymphoblastoid cell lines producing Epstein-Barr-like viruses.

Comparisons of early antigens (EA) of EBV-related lymphotropic herpes virus of Old World primates have proved difficult to accomplish because antigen levels are low in infected cells and the ratio of virus capsid antigen to EA is generally high. To overcome these difficulties, we have developed a procedure which combines antigen stimulation with inhibition of late virus functions and results in the selective stimulation of EA. Using this procedure, we have examined the EA of EBV, herpesvirus papio, h. pongo, and h. pan. The results show that the EA of these viruses are composed of both R (restricted) and D (diffuse) components and that the EA, while related, are distinguishable.

Animals↗

High proliferative activity excludes dermatofibroma: report of the utility of MIB-1 in the differential diagnosis of selected fibrohistiocytic tumors.

CONTEXT: Dermatofibroma is a benign fibrohistiocytic tumor composed of a mixture of fibroblastic and histiocytic cells. The diagnosis of this tumor is generally uncomplicated; however, rare variants may be difficult to distinguish from malignant fibrohistiocytic tumors. Deep penetrating dermatofibroma may be difficult to distinguish from dermatofibrosarcoma protuberans, and pseudosarcomatous dermatofibroma and dermatofibroma with monster giant cells share morphologic similarities with malignant fibrous histiocytoma and atypical fibroxanthoma. OBJECTIVE: To find an immunohistochemical marker or markers that differentiate between fibrohistiocytic lesions of skin. DESIGN: We evaluated the immunophenotypic characteristics of 83 fibrohistiocytic tumors (36 typical dermatofibromas, 16 cases of dermatofibrosarcoma protuberans, 16 malignant fibrous histiocytomas, and 15 atypical fibroxanthomas) using antibodies against MIB-1 (Ki-67), factor XIIIa, CD34 (HPCA-1), HHF35 (muscle-specific actin), 1A4 (smooth muscle actin), cytokeratin (AE1/AE3, CAM 5.2, and 34betaE12), S100 protein, and desmin. RESULTS: A high proliferative index detected by MIB-1 staining excluded the possibility of dermatofibroma and was diagnostically useful in separating this entity from dermatofibrosarcoma protuberans, malignant fibrous histiocytoma, and atypical fibroxanthoma. A low proliferative index, however, could not differentiate dermatofibroma from dermatofibrosarcoma protuberans. Factor XIIIa reactivity was not helpful for the diagnosis of dermatofibroma, whereas CD34 reactivity was statistically significant in the diagnosis of dermatofibrosarcoma protuberans. The sensitivity of these 2 markers is low and therefore of questionable practical diagnostic value. CONCLUSION: Evaluation of the proliferative index may further assist in distinguishing dermatofibroma from dermatofibrosarcoma protuberans, atypical fibroxanthoma, and malignant fibrous histiocytoma.

Biomarkers, Tumor↗

Small-subunit rRNA processome proteins are translationally regulated during differentiation of Trypanosoma cruzi.

We used differential display to select genes differentially expressed during differentiation of epimastigotes into metacyclic trypomastigotes in the protozoan parasite Trypanosoma cruzi. One of the selected clones had a sequence similar to that of the small-subunit (SSU) processome protein Sof1p, which is involved in rRNA processing. The corresponding T. cruzi protein, TcSof1, displayed a nuclear localization and is downregulated during metacyclogenesis. Heterologous RNA interference assays showed that depletion of this protein impaired growth but did not affect progression through the cell cycle, suggesting that ribosome synthesis regulation and the cell cycle are uncoupled in this parasite. Quantitative PCR (qPCR) assays of several SSU processome-specific genes in T. cruzi also showed that most of them were regulated posttranscriptionally. This process involves the accumulation of mRNA in the polysome fraction of metacyclic trypomastigotes, where TcSof1 cannot be detected. Metacyclic trypomastigote polysomes were purified and separated by sucrose gradient sedimentation. Northern blot analysis of the sucrose gradient fractions showed the association of TcSof1 mRNA with polysomes, confirming the qPCR data. The results suggest that the mechanism of regulation involves the blocking of translation elongation and/or termination.

Animals↗

Clinical and pathologic differential diagnosis of selected potential bioterrorism agents of interest to pediatric health care providers.

The early recognition of potential bioterrorism agents has been of increasing concern in recent years. The Centers for Disease Control and Prevention has categorized and listed biological terrorism agents. Although any or all of the highest risk biological agents (including inhalation anthrax, pneumonic plague, smallpox, tularemia, botulism, and viral hemorrhagic fevers) can be seen in the pediatric patient, several agents might closely resemble--at least in their initial stages-some of the more common childhood illnesses. The awareness of these similarities and, more importantly,their differences, are critical for all health care professionals. Selected examples of some typical childhood illnesses are presented and then compared with three of the most virulent biological agents (smallpox, anthrax and plague) that might be used in a bioterrorism attack.

Animals↗

Defective B-cell-negative selection and terminal differentiation in the ICF syndrome.

Immunodeficiency, centromeric region instability, and facial anomalies (ICF) syndrome is a rare autosomal recessive disease. Mutations in the DNA methyltransferase 3B (DNMT3B) gene are responsible for most ICF cases reported. We investigated the B-cell defects associated with agammaglobulinemia in this syndrome by analyzing primary B cells from 4 ICF patients. ICF peripheral blood (PB) contains only naive B cells; memory and gut plasma cells are absent. Naive ICF B cells bear potentially autoreactive long heavy chain variable regions complementarity determining region 3's (V(H)CDR3's) enriched with positively charged residues, in contrast to normal PB transitional and mature B cells, indicating that negative selection is impaired in patients. Like anergic B cells in transgenic models, newly generated and immature B cells accumulate in PB. Moreover, these cells secrete immunoglobulins and exhibit increased apoptosis following in vitro activation. However, they are able to up-regulate CD86, indicating that mechanisms other than anergy participate in silencing of ICF B cells. One patient without DNMT3B mutations shows differences in immunoglobulin E (IgE) switch induction, suggesting that immunodeficiency could vary with the genetic origin of the syndrome. In this study, we determined that negative selection breakdown and peripheral B-cell maturation blockage contribute to agammaglobulinemia in the ICF syndrome.

Adolescent↗

Metastatic behavior and cell surface properties of HT-29 human colon carcinoma variant cells selected for their differential expression of sialyl-dimeric Le(x)-antigen.

Immunochemical studies of human colorectal carcinoma with various monoclonal antibodies against Le(X)-related carbohydrate antigens previously revealed that the amount of sialyl-dimeric Le(X) antigen (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-R: SLX) associated with metastatic lesions was greater than in the primary tumors. To assess whether an experimental model can be used to study the direct relationship between this carbohydrate antigen and the tumor cell's metastatic behavior, we selected variant cells with increased surface SLX from established human colon carcinoma cell line HT-29. The cells in the upper 5% or lower 5% population in fluorescence intensity after reacting with a monoclonal antibody, FH6, were retrieved separately by a fluorescence-activated cell sorter and propagated. After three- or four-times selection, we obtained stable cell lines with low and high cell surface SLX antigens (HT-29 M1 and HT-29 M2, respectively). Binding of monoclonal antibody FH6 was detected to glycolipids extracted from HT-29 M2 cells but not from HT-29 M1 cells. Glycoprotein components having reactivity with monoclonal antibody FH6 were below the detectable level. HT-29 M2 cells injected intrasplenically into nude mice showed a slightly reduced incidence of metastasis to lung, liver and lymph nodes than did HT-29 M1 cells. Subsequently we found that SLX antigen was not detectable by immunohistochemical examination of these tumor cells grown in nude mice. Re-established cell line from nude mice xenografts expressed SLX antigen in vitro.

Animals↗