Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “subtype”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources
PubMed2002

Subtyping of bacterial foodborne pathogens.

Phenotype-based and DNA-based subtyping methods allow for differentiation of bacterial isolates beyond the species and subspecies level. Bacterial subtyping methods not only have improved our ability to detect and track foodbome disease outbreaks, but also represent tools to track sources of bacterial contamination throughout the food system. The use of subtyping methods furthermore provides an opportunity to better understand the population genetics, epidemiology, and ecology of different foodbome pathogens. The last 5 years have seen tremendous advancement in the development of sensitive, rapid, automated, and increasingly easy-to-use molecular subtyping methods for a variety of different bacterial foodborne pathogens. This review will highlight key aspects of different subtyping methods for bacterial foodborne pathogens and provide examples of their applications in public health, food safety, epidemiology, and population genetics. Molecular subtyping and characterization methods may also facilitate the development of a novel framework for tracking, preventing, and regulating foodborne bacterial diseases, which is based on evolutionary relationships and genetic characteristics rather than traditional species definitions.

Bacterial Typing Techniques↗
PubMed2000

Does the ICD 10 classification accurately describe subtypes of borderline personality disorder?

The aim of the paper is to explore whether the division of borderline personality disorder, as described in the DSM classification, into impulsive and borderline subtypes of emotionally unstable personality disorder in the ICD classification of personality disorder, is a valid division. The self-report questionnaire responses of 288 referrals to a personality disorder service were rated on each of the eight criteria for DSM-III-R diagnosis of borderline personality disorder. Factor analysis identified two factors; factor one closely corresponds with the borderline subtype of ICD10, whilst factor two closely corresponds with the impulsive subtype of ICD10. Criteria common to both factors unstable relationships and identity confusion - were considered core features of borderline personality disorder. The pattern of occurrence of the two factors was similar to the complex binary picture described by ICD10. However there were also differences. Firstly, identity confusion is found to be a core feature of both our factors, and this does not conform to the restriction of identity confusion to the borderline subtypes in ICD10. Secondly, we found a residual pool of undifferentiated borderline patients and a small group of pure non-impulsive borderline patients who are not currently accommodated within the ICD10 emotionally unstable personality disorder. We conclude that future classifications of this disorder should accommodate four subtypes, and suggest these subtypes have implications for treatment and further research.

Adult↗
PubMed2006

Circulating proteasomes are functional and have a subtype pattern distinct from 20S proteasomes in major blood cells.

BACKGROUND: 20S proteasomes, the proteolytic core particles of the major intracellular protein degradative pathway, are potential disease markers because they are detectable in human plasma as circulating proteasomes and their concentrations are increased in patients suffering from various diseases. To investigate the origin of circulating proteasomes, we compared some of their features with those of proteasomes isolated from major blood cells. METHODS: We isolated circulating proteasomes from the plasma of 2 patients with rheumatoid arthritis and 2 with systemic lupus erythematosus and from human plasma from healthy donors. We purified the proteasomes to apparent homogeneity and then used electron microscopy for imaging and chromatography for subtype spectrum analysis. We compared subtype results with those from 20S proteasomes purified from 4 major blood cell populations. We also tested proteasomes for enzymatic activity and immunosubunit content. RESULTS: Circulating proteasomes from plasma of healthy donors and from patients with autoimmune disease were found to have the same size and shape as erythrocyte proteasomes, be proteolytically active, and contain standard- and immunosubunits. Chromatography revealed 6 circulating proteasome subtype peaks in healthy donor plasma and 7 in patient donor plasma. Proteasomes from erythrocytes had 3 subtype peaks and those of monocytes, T-lymphocytes, and thrombocytes each had 5 different subtype peaks. CONCLUSION: Circulating proteasomes were intact and enzymatically active in plasma from healthy donors and from patients with autoimmune disease. Because the subtype patterns of circulating proteasomes clearly differ from those of proteasomes from blood cells, these cells cannot be regarded as a major source of circulating proteasomes.

Adolescent↗
PubMed2005

Genetic contributions to subtypes of aggression.

Boys and girls may display different styles of aggression. The aim of this study was to identify subtypes of aggression within the Child Behavior Checklist (CBCL) aggression scale, and determine their characteristics for both sexes. Maternal CBCL ratings of 7449 7-year-old twin pairs were analyzed using principal components analyses to identify subtypes of aggression, and structural equation modeling to carry out genetic analyses. Two aggression subtypes were identified: relational and direct aggression. The correlation between these subtypes was .58 for boys and .47 for girls. Boys had higher mean scores for both subtypes of aggression, but sex differences were largest for direct aggression. For relational aggression, 66% of the variance was due to additive genetic influences, 16% to shared environment and 18% to nonshared environment. For direct aggression, additive genetic effects accounted for 53% of the variance in males and 60% in females, shared environment explained 23% of the variance in males and 13% in females, and nonshared environmental effects explained 24% of the variance in males and 27% in females. Covariance between the aggression subtypes was mostly accounted for by additive genetic (55% for boys, 58% for girls) and shared environmental influences (33% for boys, 30% for girls). Direct and relational aggression were both influenced by one underlying set of shared environmental factors, but only partly by the same genes (the genetic correlation was .54 for boys and .43 for girls). These findings may have implications for how aggressive behavior should be assessed in boys and girls.

Aggression↗
PubMed1998

Comparison of two reverse transcription-polymerase chain reaction methods for detection of AML1/ETO rearrangement in the M2 subtype of acute myeloid leukaemia.

Two reverse transcription-polymerase chain reaction methods to detect the AML1/ETO rearrangement in the M2 subtype of acute myeloid leukaemia those of Downing et al. (Blood 1993; 81: 2860-5) and Satake et al. (Br J Haematol 1995; 91: 892-8) were evaluated. Bone marrow samples, one at diagnosis and two in complete remission from a patient with M2 subtype of acute myeloid leukaemia, with t(8;21), were analysed using both methods. The Kasumi-1 cell line was used as a positive control and a patient with M3 subtype of acute myeloid leukaemia as a negative control. To confirm the feasibility of Satake's method a group of 35 patients with subtypes of acute myeloid leukaemia at diagnosis were studied. The method of Downing requires Southern blotting and hybridization with a specific probe because it often generates non-specific amplification products. By contrast, the method of Satake yields only a single amplification product, using one single round of PCR in samples at diagnosis, or two rounds in complete remission samples. The sensitivity of this method allows the detection of a single Kasumi-1 cell in 10(6) normal cells. The AML1/ETO rearrangement was observed in 5 of the 35 cases of acute myeloid leukaemia at diagnosis (14.3%) and in 3 of the 14 cases of M2 subtype of acute myeloid leukaemia (21.4%). The two remaining positive cases corresponded to the acute myeloid leukaemia subtypes M4 and M6. The results indicate that the method of Satake better meets the requirements of the clinical laboratory due to its greater simplicity, specificity, sensitivity and feasibility, thus making it more appropriate for use in diagnosing and monitoring minimal residual disease.

Base Sequence↗
PubMed1999

Young novice driver subtypes: relationship to high-risk behavior, traffic accident record, and simulator driving performance.

Two studies were undertaken to obtain empirical support for the existence of driver subtypes in the young novice driver population. In Study 1, 198 participants (55% male) aged 16 to 19 completed an extensive self-report questionnaire. Five novice driver subtypes were identified through a cluster analysis of personality and driving-related measures. Two relatively high-risk or deviant subtypes (Clusters 1 and 5) were identified, characterized by high levels of driving-related aggression, competitive speed, driving to reduce tension, sensation seeking, assaultiveness, and hostility. The individuals in Cluster 5 also reported low levels of emotional adjustment and high levels of depression, resentfulness, and irritability. In Study 2, a subset of participants from each of the subtypes drove several scenarios in a driving simulator. The subtypes differed in their responses to an emergency situation and several potential traffic hazards. They also differed in the proficiency with which they could control their attention among concurrent tasks in high-workload situations. Most of the significant differences were related to lower levels of driving skill among the two most deviant subtypes (Clusters 1 and 5). The potential applications of this research include the design of training programs and other countermeasures to address the young novice driver crash problem.

Accidents, Traffic↗
PubMed2004

Axon branching and synaptic bouton phenotypes in GABAergic nonpyramidal cell subtypes.

GABAergic nonpyramidal cells, cortical interneurons, consist of heterogeneous subtypes differing in their axonal field and target selectivity. It remains to be investigated how the diverse innervation patterns are generated and how these spatially complicated, but synaptically specific wirings are achieved. Here, we asked whether a particular cell type obeys a specific branching and bouton arrangement principle or differs from others only in average morphometric values of the morphological template common to nonpyramidal cells. For this purpose, we subclassified nonpyramidal cells within each physiological class by quantitative parameters of somata, dendrites, and axons and characterized axon branching and bouton distribution patterns quantitatively. Each subtype showed a characteristic set of vertical and horizontal bouton spreads around the somata. Each parameter, such as branching angles, internode or interbouton intervals, followed its own characteristic distribution pattern irrespective of subtypes, suggesting that nonpyramidal cells have the common mechanism for formation of the axon branching pattern and bouton arrangement. Fitting of internode and interbouton interval distributions to the exponential indicated their apparent random occurrence. Decay constants of the fitted exponentials varied among nonpyramidal cells, but each subtype expressed a particular set of interbouton and internode interval averages. The distinctive combination of innervation field shape and local axon phenotypes suggests a marked functional difference in the laminar and columnar integration properties of different GABAergic subtypes, as well as the subtype-specific density of inhibited targets.

Analysis of Variance↗
PubMed1998

alpha-Thalassemia Subtyping and the Detection of Silent Mutations by High-Resolution Fragment Analysis and DNA Sequencing.

Background: Sets of polymerase chain reaction (PCR) primers were used that make it possible to study subtypes of the most prevalent mutations that cause alpha-thalassemia (-alpha3.7 deletions). These primers (Dev and C3, Dev and C9c) can be used in PCR to amplify regions that are characteristic of the three - alpha3.7 deletion subtypes (alpha3.7i, alpha3.7ii, alpha3.7iii). These subtypes are important because the type of alpha-chain deletion can affect the level of alpha-globin production. Methods and Results: The PCR products were screened using automated high-resolution electrophoresis on a DNA sequencer. Subtypes were then identified by automated DNA sequencing. During the screening for subtypes with high-resolution fragment analysis, new fragments were detected that were slightly different from the expected size. DNA sequencing of these fragments demonstrated the presence of three mutations that had not been described or fully characterized before. Conclusions: High-resolution fragment analysis is a convenient way to detect alpha-thalassemia subtypes, and DNA sequencing of silent mutations can lead to a better understanding of the cause of these mutations.

Journal Article↗
PubMed2003

Effect of cyproterone acetate on alpha1-adrenoceptor subtypes in rat vas deferens.

Gonadal hormones regulate the expression of alpha1-adrenoceptor subtypes in several tissues. The present study was carried out to determine whether or not cyproterone acetate, an anti-androgenic agent, regulates the alpha1-adrenoceptor subtypes that mediate contractions of the rat vas deferens in response to noradrenaline. The actions of subtype selective alpha1-antagonists were investigated in vas deferens from control and cyproterone acetate-treated rats (10 mg/day, sc, for 7 days). Prazosin (pA2 approximately 9.5), phentolamine (pA2 approximately 8.3) and yohimbine (pA2 approximately 6.7) presented competitive antagonism consistent with activation of alpha1-adrenoceptors in vas deferens from both control and treated rats. The pA2 values estimated for WB 4101 ( approximately 9.5), benoxathian ( approximately 9.7), 5-methylurapidil (approximately 8.5), indoramin ( approximately 8.7) and BMY 7378 ( approximately 6.8) indicate that alpha1A-adrenoceptors are involved in the contractions of the vas deferens from control and cyproterone acetate-treated rats. Treatment of the vas deferens from control rats with the alpha1B/alpha1D-adrenoceptor alkylating agent chloroethylclonidine had no effect on noradrenaline contractions, supporting the involvement of the alpha1A-subtype. However, this agent partially inhibited the contractions of vas deferens from cyproterone acetate-treated rats, suggesting involvement of multiple receptor subtypes. To further investigate this, the actions of WB 4101 and chloroethylclonidine were reevaluated in the vas deferens from rats treated with cyproterone acetate for 14 days. In these organs WB 4101 presented complex antagonism characterized by a Schild plot with a slope different from unity (0.65 0.05). After treatment with chloroethylclonidine, the complex antagonism presented by WB 4101 was converted into classical competitive antagonism, consistent with participation of alpha1A-adrenoceptors as well as alpha1B-adrenoceptors. These results suggest that cyproterone acetate induces plasticity in the alpha1-adrenoceptor subtypes involved in the contractions of the vas deferens.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2003

Therapeutic response to benzodiazepine in panic disorder subtypes.

CONTEXT: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine. OBJECTIVES: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day), compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes. TYPE OF STUDY: Randomized study with clonazepam and placebo. SETTING: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. PARTICIPANTS: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old. PROCEDURES: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory. MAIN MEASUREMENTS: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale. RESULTS: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001) and decrease in anxiety (p = 0.024). In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam. CONCLUSION: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes.

Adolescent↗
PubMed1995

Effects of ovarian steroids on hypothalamic opioid receptor subtypes in ovariectomized ewes: regional changes in density and affinity.

The negative feedback regulation by ovarian steroids of luteinizing hormone secretion may be partially mediated by a hypothalamic endogenous opioid mechanism. This could be affected by ovarian steroid-regulated changes in hypothalamic opioid receptor binding mechanisms. In this report we show that in the presence of blocking concentrations of site-selective opioid analogues, [3H] diprenorphin homogeneously labelled mu, delta or kappa receptor subtypes respectively. Using this receptor binding model, we characterized each opioid receptor subtype in the hypothalamic preoptic area and medio-basal hypothalamus of ovariectomized (OVX) and OVX plus progesterone- or oestradiol-17 beta (OE2)-treated ewes. In the preoptic area, progesterone treatment did not influence the affinity or capacity of delta or kappa receptor binding sites, but significantly reduced mu receptor subtype content (20% less than control) with no statistically significant change in affinity. There was no effect of OE2 on either the affinity or capacity of each opioid receptor subtype in this area. In the mediobasal hypothalamus, progesterone treatment significantly decreased delta subtype receptor affinity (22 +/- 11 nM vs control 7 +/- 2 nM) and increased binding capacity (78 +/- 9 fmol/mg protein vs control 37 +/- 16 fmol/mg protein). OE2 treatment had a similar, though more profound effect on affinity (51 +/- 17 nM) and binding capacity (139 +/- 26 fmol/mg protein) at the delta receptor binding site. There were no significant changes in the affinity or capacity of mu or kappa binding sites in the medio-basal hypothalamus. These results indicate that steroid hormones modulate hypothalamic opioid receptors in the OVX ewe in a receptor subtype- and region-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Charge heterogeneity of the AT1 angiotensin II receptor subtype in the rat lung.

In order to obtain more information on the molecular structure of the angiotensin II (Ang II) binding sites from whole rat lung membranes these were characterized by isoelectric focusing (IEF) and SDS-PAGE. Whereas a single population of Ang II receptor sites was identified (Kd = 2.2 +/- 0.3 nmol/l; Bmax = 203.9 +/- 15.8 fmol/mg protein) by Scatchard analysis, using IEF three Ang II binding isoforms were observed; a major band which migrated to isoelectric point (pI) 6.7, and two minor bands with pI values of 6.5 and 6.3. Specific binding of 125I-Ang II to rat lung membrane preparations was sensitive to Losartan, a non-peptide AT1 receptor subtype antagonist, but was unaffected by the AT2 receptor subtype antagonist CGP42112A. Immunoblotting analyses on SDS gels, using a monoclonal antibody specific to the AT1 receptor, showed two immunoreactive protein species of 45 and 48 kDa. Enzymic deglycosylation using recombinant N-glycanase did not alter the molecular weight patterns of the AT1 receptor subtype. The results of the present study demonstrated that the Ang II receptor population in the whole rat lung consists solely of the AT1 receptor subtype and that the AT2 receptor subtype is absent. In addition, the data showed the existence of charge heterogeneity of the AT1 receptor subtype, and suggest that glycosylation probably does not contribute to its charge heterogeneity.

Angiotensin II↗
PubMed1996

Changes in the binding characteristics of the mu, delta and kappa subtypes of the opioid receptor in the hypothalamus of the normal cyclic ewe and in the ovariectomised ewe following treatment with ovarian steroids.

The mu, delta and kappa opioid receptor subtypes were measured across the oestrous cycle of the ewe and in ovariectomised (OVX) ewes treated with oestrogen and/or progesterone. We have used a subtype-specific opioid receptor binding assay, in which [3H]diprenorphine non-preferentially labelled each receptor subtype in the presence of blocking concentrations of site-specific opioid analogues. The density and affinity of each receptor subtype was measured in the preoptic area (POA) of the hypothalamus and the mediobasal hypothalamus (MBH). Normally cycling ewes were killed during the luteal phase of the oestrous cycle and at various times after an injection of a synthetic prostaglandin (cloprostenol) to synchronise the onset of the follicular phase. OVX ewes were either untreated as controls (n = 4) or treated with oestrogen (n = 4), progesterone (n = 4) or oestrogen and progesterone combined (n = 4). The total number of opioid receptors did not alter across the oestrous cycle or with steroid hormone treatment. In the POA, the mean (+/- S.E.M.) number of delta receptors was significantly (P < 0.05) greater during the luteal phase than 24 h into the follicular phase (133 +/- 45 vs 35 +/- 8 fmol/mg protein). A significantly (P < 0.05) greater number of delta receptors was also found in the OVX progesterone-treated ewes compared with the control animals (172 +/- 9 vs 39 +/- 4 fmol/mg protein). In the MBH, the number of delta receptors was significantly (P < 0.01) greater in ewes killed 56 h after prostaglandin than luteal-phase ewes (184 +/- 40 vs 51 +/- 7 fmol/mg protein). The number of mu receptors in both the POA and the MBH was also significantly (P < 0.05) higher in the 56-h group than in the 12-h group. A similar trend was also observed in the steroid-treated animals, although differences did not reach statistical significance. The delta:mu ratio in the POA was significantly (P < 0.05) higher in the luteal-phase animals than any of the other groups killed after a cloprostenol injection that causes luteolysis. Similarly the ratio of delta receptor density to mu receptor density was greater (P < 0.05) in the OVX progesterone-treated ewes than in the OVX control ewes. No differences were found in the kappa receptor density across the cycle or with different steroid treatments. These data suggest that the relative proportions of the delta and mu subtypes of the opioid receptor in the hypothalamus change during the oestrous cycle. Regulation appears to be due to the feedback effects of ovarian steroids with progesterone altering the delta:mu ratio. In the MBH, there was a general increase in both delta and mu subtypes during the follicular phase of the oestrous cycle. This may explain, in part, how the responsiveness of the GnRH/LH axis to opioid peptides and antagonists changes across the cycle.

Animals↗
PubMed2002

Differentiation of multiple sclerosis subtypes: implications for treatment.

There has been tremendous progress in the immunomodulatory treatment of multiple sclerosis (MS) during recent years. With the introduction of interferon-beta, glatiramer acetate and mitoxantrone (recently registered for MS in the US), there are at least three therapeutic strategies that have proven effective in large phase III studies. However, not all patients with MS respond well to treatment with these drugs. This may largely be a consequence of disease heterogeneity. From a clinical perspective, patients with different disease courses show different treatment responses. Patients with relapsing-remitting MS are more likely to respond to immunomodulatory therapy than those with a progressive disease course. Studies of patients with secondary progressive MS have yielded inconsistent results and, so far, there has been no positive phase III study of immunomodulatory therapy in patients with primary progressive MS. Pathological evidence indicates that subtyping based on clinical findings alone does not reflect actual disease heterogeneity. In a large series of biopsy and autopsy specimens, at least four subtypes could be identified with respect to oligodendrocyte/myelin pathology and immunopathology. As long as the only method of identifying subtypes of disease is histopathology, differential therapy will remain a future goal. Thus, there is an urgent need for in vivo markers of immunopathogenesis in an individual patient that would allow treatment to be specifically directed towards a given pathological focus. However, at least from a theoretical point of view, some therapeutic approaches appear very attractive. Plasmapheresis and/or intravenous immunoglobulins could most plausibly be the best approach for the immunopathological subtype of MS, which is characterised by antibody and complement deposition next to demyelinated axons, in order to remove antibodies. The subtype of MS that is associated with heavy macrophage activation, T cell infiltration and expression of inflammatory mediator molecules, including tumour necrosis factor-alpha, may be most likely to respond to immunomodulation with interferon-beta or glatiramer acetate. There are other subtypes of MS in which viral infection or oligodendrocyte degeneration, rather than autoimmunity, appear to play a role. It is possible that these could benefit from antiviral therapy, oligodendrocyte protection or oligodendrocyte transplantation, although therapies based on these latter approaches have yet to be developed.

Adrenal Cortex Hormones↗
PubMed2004

Contrast-enhanced high-resolution MRI of invasive breast cancer: correlation with histopathologic subtypes.

OBJECTIVE: We sought to determine whether contrast-enhanced MRI could aid in the identification of the histopathologic subtypes of invasive ductal carcinoma. MATERIALS AND METHODS: We evaluated the contrast-enhanced MR images obtained in 62 women with invasive ductal carcinoma of no special type. The presence or absence of three distinct MRI findings-linear enhancement, a serrated border, and delayed rim enhancement-was evaluated. Classification and regression tree analyses were performed to construct the most efficient algorithm for predicting histopathologic subtype on the basis of dynamic MRI features. RESULTS: Histopathologic subtypes of the invasive ductal carcinomas were scirrhous carcinoma in 22 patients, solid tubular carcinoma in 14, and papillotubular carcinoma in 26. A lesion with a serrated border was observed in 28 (45.2%) of the 62 patients. Delayed rim enhancement was seen in 23 (37.1%) and linear enhancement in 20 (32.3%). Scirrhous carcinomas were closely associated with a serrated border (20/22 or 90.9%, p < 0.0001). Delayed rim enhancement was frequently observed in solid tubular carcinomas (12/14 or 85.7%, p < 0.0001) but was not typically seen in scirrhous carcinomas (1/22 or 4.5%, p < 0.0001). Linear enhancement showed relatively high prevalence in papillotubular carcinomas (13/26 or 50%) and low prevalence in solid tubular carcinomas (1/22 or 7%, p < 0.02). Histopathologic subtypes of invasive breast carcinoma of no special type could be correctly identified in 47 (75.8%) of 62 lesions using the diagnostic algorithm generated by the classification and regression tree analyses. CONCLUSION: MRI features showed a close relationship with histopathologic subtypes of invasive ductal carcinoma of no special type. Contrast-enhanced MRI can be a noninvasive diagnostic tool for histopathologic subtypes of invasive breast cancer.

Adult↗
PubMed2006

Activation of Wnt/beta-catenin signaling in distinct histologic subtypes of human germ cell tumors.

The molecular signaling pathways mediating human germ cell tumor (GCT) formation and progression are poorly understood despite a large number of studies detailing recurrent cytogenetic abnormalities. Germ cell tumors consist of multiple histologic subtypes and can also be divided into infantile/childhood or adolescent/adult tumors as well as gonadal or nongonadal sites of origin. All of these parameters are important in defining clinical outcome and in understanding the pathogenesis of these tumors. We utilized complementary DNA (cDNA) microarray analysis to identify differences in signal transduction pathways between 2 histologic subtypes of malignant ovarian GCTs (dysgerminomas versus ovarian endodermal sinus tumors). Hierarchical cluster analysis using only the genes involved in Wnt/beta-catenin signaling was able to distinguish these 2 tumor subtypes from each other. Wnt13 and beta-catenin showed significant differential expression patterns between the 2 tumor subtypes, and the results were confirmed by semiquantitative reverse transcriptase-polymerase chain reaction. Additional GCTs were studied for the expression of other members of Wnt/beta-catenin signaling, including Wnt13, frizzled, disheveled, low-density lipoprotein receptor-related protein 6, and beta-catenin. Differential expression levels were identified for several histologic subtypes of human GCTs. Finally, we prepared tissue microarrays containing GCTs from 83 different patients and demonstrated high levels of beta-catenin protein expression in 100% and nuclear accumulation in approximately 50% to 70% of all endodermal sinus tumors and immature teratomas (ITs). This pattern was independent of the patient's age. No nuclear accumulation of beta-catenin was observed in germinomas, embryonal carcinomas, or choriocarcinomas. These results indicate that activation of Wnt/beta-catenin signaling plays an important role in the pathogenesis of 2 histologic subtypes of human GCTs.

Adolescent↗
PubMed2001

Characterization of alpha-adrenoceptor subtypes in smooth muscle of equine ileum.

OBJECTIVE: To determine the concentration and binding characteristics of alpha-adrenoceptor subtypes in smooth muscle cell membranes of equine ileum. SAMPLE POPULATION: Segments of longitudinal and circular smooth muscle from the ileum of 8 male and 8 female adult horses. PROCEDURE: Distribution of alpha-adrenoceptor subtypes was assessed by use of radioligand binding assays incorporating [3H]-prazosin and [3H]-rauwolscine, highly selective alpha1- and alpha2-adrenoceptor antagonists, respectively. Characterization of adrenoceptor subtypes was performed by use of binding inhibition assays. RESULTS: On the basis of binding affinity for specific radioligands, low- and high-affinity alpha1- and alpha2-adrenoceptors were detected. Concentration of low-affinity alpha2-adrenoceptors was significantly greater in male horses, compared with females. Competition studies confirmed the specificity of the radioligands used in the binding assays. Alpha1-adrenoceptors of both subtypes in male and female horses had a higher affinity for prazosin than phentolamine, whereas yohimbine did not compete with the radioligand for binding. For alpha2-adrenoceptors regardless of subtype, potency of inhibition elicited by each drug varied between sexes. In males, yohimbine was a more potent inhibitor than phentolamine, which was more potent than prazosin. In females, yohimbine was more potent than prazosin, which was more potent than phentolamine. CONCLUSIONS AND CLINICAL RELEVANCE: High- and low-affinity alpha1- and alpha2-adrenoceptors were detected in smooth muscle of equine ileum. Because alpha-adrenoceptor subtypes, particularly alpha2-adrenoceptors, are involved in the regulation of gastrointestinal tract function, characterization of these receptors may represent the basis for development of new therapeutic strategies for the control of gastrointestinal disturbances in horses.

Adrenergic alpha-Antagonists↗
PubMed2003

Beta-adrenergic receptor subtypes that mediate ractopamine stimulation of lipolysis.

Ractopamine HCl is an beta-adrenergic receptor (betaAR) ligand that was recently approved for use in swine to enhance carcass leanness. The RR stereoisomer of ractopamine is the most active of the four stereoisomers exhibiting the highest affinity and signaling response. The RR isomer exhibits selective activation of the porcine beta2AR, which might limit the lipolytic response to ractopamine because the betaAR is the predominant subtype in swine adipocytes and may mediate most of the lipolytic response. Therefore, we determined the betaAR subtypes that mediate the lipolytic response to ractopamine in swine adipocytes. In order to confirm the predominant role of the beta1AR in porcine adipocytes, isoproterenol-stimulated lipolysis was inhibited by increasing doses of subtype-selective antagonists. Inhibition curves were biphasic using beta1AR antagonists (CGP 20712A and bisoprolol) and curve analysis indicated that both beta1AR an beta2AR contributed to lipolysis with 50 to 60% of the response coming from the beta1AR. Inhibition with the beta2AR antagonist clenbuterol revealed only one class of betaAR that closely approximated the kinetics of the beta1AR. When the RR isomer of ractopamine was the lipolytic agent, similar results to isoproterenol were observed, except that the estimated contribution of the beta1AR was 38%. That beta2AR antagonists did not detect a contribution of the beta2AR to lipolysis may indicate that the beta1AR masked the response to the beta2AR. Dose titration with the RR isomer in the presence of a saturating concentration of beta1AR or beta2AR antagonists indicated that each subtype was present in sufficient quantities to stimulate lipolysis near maximally. Data indicate that both the beta1AR and beta2AR are functionally linked to lipolysis in swine adipocytes and that ractopamine activates each subtype. The RR isomer of ractopamine stimulated adenosine 3',5'-cyclic phosphate accumulation with equal efficacy to isoproterenol through the cloned porcine beta2AR, but was only 35% as efficacious through the cloned porcine beta1AR. These data confirm the beta2AR selectivity of the RR stereoisomer, but suggest the partial agonism through the beta1AR is sufficient to activate lipolysis through both subtypes in swine adipocytes.

Adipocytes↗