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PubMed2002

Differentiation of subtypes of renal cell carcinoma on helical CT scans.

OBJECTIVE: The purpose of our study was to differentiate subtypes of renal cell carcinoma on helical CT scans. MATERIALS AND METHODS: We reviewed CT scans of four subtypes of renal cell carcinoma: 76 conventional (clear cell), 19 papillary, 13 chromophobe, and two collecting duct. Biphasic CT scans (unenhanced, corticomedullary, and excretory phase scans) were obtained in 61 patients, and monophasic CT scans (unenhanced and excretory phase scans) in 49. We compared patient age and sex; tumor size; degree and pattern (homogeneous, heterogeneous, predominantly peripheral) of enhancement; presence or absence of calcification; and tumor-spreading patterns including perinephric change, venous invasion, and lymphadenopathy in four subtypes. RESULTS: Conventional renal carcinoma showed stronger enhancement than the other subtypes (p < 0.05): 106 +/- 48 H (mean +/- SD) in the corticomedullary phase and 62 +/- 25 H in the excretory phase. The sensitivity and specificity for differentiating conventional renal carcinoma from the other subtypes were 74% and 100% when 84 H was used as the cutoff value in the corticomedullary phase and 84% and 91% when 44 H was used as the cutoff value in the excretory phase. Conventional (84%), papillary (74%), and collecting duct (100%) renal carcinomas tended to show heterogeneous or predominantly peripheral enhancement, whereas chromophobe renal carcinoma (69%) usually showed homogeneous enhancement. Calcification was more common in papillary (32%) and chromophobe (38%) renal carcinomas than in conventional renal carcinoma (11%) (p < 0.05). Perinephric change and venous invasion were not noted in chromophobe renal carcinoma, whereas both were common in collecting duct renal carcinoma. CONCLUSION: For the differentiation of the subtypes of renal cell carcinoma, degree of enhancement is the most valuable parameter; enhancement pattern, the presence or absence of calcification, and tumor-spreading patterns can serve supplemental roles in the identification of the subtype of renal cell carcinoma.

Aged↗
PubMed2006

mRNA expression and binding sites for alpha2-adrenergic receptor subtypes in muscle layers of the ileum and spiral colon of dairy cows.

OBJECTIVE: To measure maximum binding capacity (B(max)) and levels of mRNA expression for alpha(2)-adrenergic receptor (AR) subtypes in ileal and colonic muscle layers of healthy dairy cows. SAMPLE POPULATION: Ileal and colonic muscle specimens from 6 freshly slaughtered cows. PROCEDURES: Ileal and colonic muscle layers were obtained by scraping the mucosa and submucosa from full-thickness tissue specimens. Level of mRNA expression for alpha(2)-AR subtypes was measured by real-time reverse transcriptase-PCR analysis and expressed relative to the mean mRNA expression of glyceraldehyde phosphate dehydrogenase, ubiquitin, and 18S ribosomal RNA. Binding studies were performed with tritiated RX821002 ((3)H-RX821002) and subtype-selective ligands as competitors. RESULTS: mRNA expression for alpha(2AD)-, alpha(2B)-, and alpha(2C)-AR subtypes was similar in ileal and colonic muscle layers. The mRNA expression for alpha(2AD)-AR was significantly greater than that for alpha(2B)- and alpha(2C)-AR subtypes, representing 92%, 6%, and 2%, respectively, of the total mRNA. Binding competition of (3)H-RX821002 with BRL44408, imiloxan, and MK-912 was best fitted by a 1-site model. The B(max) of alpha(2AD)- and alpha(2C)-AR sub-types was greater than that of alpha(2B)-AR. The B(max) and level of mRNA expression were only correlated (r = 0.8) for alpha(2AD)-AR. Ratio of B(max) to mRNA expression for alpha(2C)-AR was similar to that for alpha(2B)-AR, but significantly greater than for alpha(2AD)-AR. CONCLUSIONS AND CLINICAL RELEVANCE: Subtypes of alpha(2)-AR in bovine intestinal muscle layers are represented by a mixture of alpha(2AD)- and alpha(2C)-ARs and of alpha(2B)-AR at a lower density. Information provided here may help in clarification of the role of AR subtypes in alpha(2)-adrenergic mechanisms regulating bovine intestinal motility.

Animals↗
PubMed1995

Molecular pharmacology of alpha 2-adrenoceptor subtypes.

alpha 2-adrenergic receptors mediate many of the physiological actions of the endogenous catecholamines adrenaline and noradrenaline, and are targets of several therapeutic agents. alpha 2-adrenoceptor agonists are currently used as antihypertensives and as veterinary sedative anaesthetics. They are also used in humans as adjuncts to anaesthesia, as spinal analgesics, and to treat opioid, nicotine and alcohol dependence and withdrawal. Three human alpha 2-adrenoceptor subtype genes have been cloned and designated alpha 2-C10, alpha 2-C4, and alpha 2-C2, according to their location on human chromosomes 10, 4 and 2. They correspond to the previously identified pharmacological receptor subtypes alpha 2A, alpha 2C and alpha 2B. The receptor proteins share only about 50% identity in their amino acid sequence, but some structurally and functionally important domains are very well conserved. The most obvious functionally important differences between the receptor subtypes are based on their different tissue distributions; e.g. the alpha 2A subtype appears to be an important modulator of noradrenergic neurotransmission in the brain. The three receptors bind most alpha 2-adrenergic drugs with similar affinities, but some compounds (e.g. oxymetazoline) are capable of discriminating between the subtypes. Clinically useful subtype selectivity cannot be achieved with currently available pharmaceutical agents. The second messenger pathways of the three receptors show many similarities, but small functional differences between the subtypes may turn out to have important pharmacological and clinical consequences. All alpha 2-adrenoceptors couple to the pertussis-toxin sensitive inhibitory G proteins Gi and G(o), but recent evidence indicates that also other G proteins may interact with alpha 2-adrenoceptors, including Gs and Gq/11. Inhibition of adenylyl cyclase activity, which results in decreased formation of cAMP, is an important consequence of alpha 2-adrenoceptor activation. Many of the physiological effects of alpha 2-adrenoceptor activation cannot, however, be explained by decreases in cAMP formation. Therefore, alternative mechanisms have been sought to account for the various effects of alpha 2-adrenoceptor activation on electrophysiologic, secretory and contractile cellular responses. Recent results obtained from studies on ion channel regulation point to the importance of calcium and potassium channels in the molecular pharmacology of alpha 2-adrenoceptors.

Adenylyl Cyclase Inhibitors↗
PubMedDate not supplied

Introduction of HIV-2 and multiple HIV-1 subtypes to Lebanon.

HIV genetic variability, phylogenetic relationships, and transmission dynamics were analyzed in 26 HIV-infected patients from Lebanon. Twenty-five specimens were identified as HIV-1 and one as HIV-2 subtype B. The 25 strains were classified into six env-C2-V3 HIV-1 subtypes: B (n = 10), A (n = 11), C (n = 1), D (n = 1), G (n = 1), and unclassifiable. Potential recombinants combining parts of viral regions from different subtypes Aenv/Dpol/Agag, Genv/Apol, and the unclassifiable-subtype(env)/unclassifiable-subtype(pol)/Agag were found in three patients. Epidemiologic analysis of travel histories and behavioral risks indicated that HIV-1 and HIV-2 subtypes reflected HIV strains prevalent in countries visited by patients or their sex partners. Spread of complex HIV-subtype distribution patterns to regions where HIV is not endemic may be more common than previously thought. Blood screening for both HIV-1 and HIV-2 in Lebanon is recommended to protect the blood supply. HIV subtype data provide information for vaccine development.

Adult↗
PubMed2003

Differential responses to IFN-alpha subtypes in human T cells and dendritic cells.

Type I IFNs (IFN-alphabeta) constitute a family of cytokines that have important antiviral and immunoregulatory properties and have been successfully used in the treatment of a wide variety of diseases. There are 12 functional human IFN-alpha subtypes and one IFN-beta subtype that signal through the common cell surface IFN-alphabetaR. To date, virtually no information is available on the specificity of IFN-alpha responses in immune cells. In this study, Janus kinase/STAT signaling and transcriptional responses to selected IFN-alpha subtypes in human T cells and dendritic cells were analyzed. Evidence for IFN-alpha subtype and cell type specificity was found. Also, differences between kinetics of expression of IFN-stimulated genes (ISGs) and in the requirements of individual ISGs for additional signaling pathways were observed. In particular, IFN-gamma-inducible protein-10 (IP-10), a key chemokine in Th1-type inflammatory diseases, was differentially regulated. In dendritic cells, it was highly induced by IFN-alpha2 and IFN-alpha21 but much less efficiently by IFN-alpha1. It was only marginally induced by these subtypes in T cells. In marked contrast to other ISGs analyzed, optimum induction of IP-10 was dependent on activation of p38 kinase(s). The observed variations (subtype-, cell type-, and ISG-related differentials) provide further insight into the complexity and plasticity of the IFN-alphabeta response. Furthermore, the novel observation that IFN-alpha1 poorly induces IP-10 is potentially of clinical importance, because this subtype may be more beneficial in cases where Th1-mediated side effects (e.g., exacerbation of autoimmune diseases) are not desirable.

Cells, Cultured↗
PubMed2006

Immunohistochemical classification of de novo, transformed, and relapsed diffuse large B-cell lymphoma into germinal center B-cell and nongerminal center B-cell subtypes correlates with gene expression profile and patient survival.

CONTEXT: Diffuse large B-cell lymphoma (DLBCL) can be assigned to prognostic subgroups, including germinal center B-cell (GCB) and activated B-cell subgroups, by using gene expression profiling and, reportedly, immunohistochemistry for CD10, Bcl-6, and multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4). OBJECTIVE: To compare 2 commercial MUM1/IRF4 antibody formulations for accuracy in subtyping DLBCL against gene expression profiling, compare subtyping to patient survival, and evaluate the usefulness of GCB and non-GCB subtyping in relapsed and transformed DLBCL. DESIGN: Evaluation of 2 commercial MUM1/IRF4 antibodies, ICSTAT/M17 and Mum-1p, by using 40 cases of de novo, relapsed, and transformed DLBCL; and comparison of the results obtained with gene expression profiling and survival. RESULTS: Immunohistochemistry predicted the gene expression profiling subtype 71.8% and 69.2% of the time overall with use of the Mum-1p and ICSTAT/M17 antibodies, respectively, and 100% and 91.7% of the time when MUM1/IRF4 expression determined subtype. Gene expression profiling and immunohistochemistry revealed nearly identical 5-year overall survival rates for the GCB vs non-GCB subtypes (68.0% for GCB vs 24.7% for non-GCB with use of gene expression profiling [P = .03] and 70.2% vs 18.4%, respectively, with use of immunohistochemistry [P < .001]). When de novo, transformed, and relapsed cases were analyzed separately, 5-year overall survival rates were also significantly different. CONCLUSIONS: Immunohistochemistry can be used to subclassify DLBCL, including a very small series of transformed and relapsed cases, into GCB and non-GCB subtypes and predict survival rates similar to those predicted by use of gene expression profiling. The 2 MUM1/IRF4 antibodies performed similarly.

B-Lymphocytes↗
PubMed1999

Identification and characterization of multiple subtypes of muscarinic acetylcholine receptors and their physiological functions in canine hearts.

M2 receptors have long been believed to be the only functional subtype of muscarinic acetylcholine receptor (mAChR) in the heart, although recent studies have provided evidence for the presence of other subtypes. We performed a detailed study to clarify this issue. In the presence of tetramethylammonium (1 microM to 10 mM), a novel K+ current with both delayed rectifying and inward rectifying properties (IKTMA) was activated in single canine atrial myocytes. 4-Aminopyridine (0.05-2 mM) also induced a K+ current (IK4AP) with characteristics similar to but distinct from those of IKTMA. Both IKTMA and IK4AP were abolished by 1 microM atropine. IK4AP, but not IKTMA, was minimized by treatment with pertussis toxin. IKTMA was markedly decreased by 4-diphenylacetoxy-N-methylpiperidine methiodide (a selective antagonist for M3 subtype) but was not altered by pirenzepine (for M1), methoctramine (for M2), and tropicamide (for M4). Tropicamide substantially reduced IK4AP, but the antagonists for other mAChR subtypes had no effects on IK4AP. By comparison, IKACh (ACh-induced K+ current) was significantly depressed by methoctramine but was unaltered by other antagonists. Results from displacement binding of [methyl-3H]N-scopolamine methyl chloride with pirenzepine, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methiodide, or tropicamide revealed the coexistence of multiple mAChR subtypes in canine atrium. Cloning of cDNA fragments and detection of mRNAs coding for M2, M3, and M4 provided further supporting evidence. Our results suggest that 1) multiple subtypes of mAChRs (M2/M3/M4) coexist in the dog heart and 2) different subtypes of mAChRs are coupled to different K+ channels. Our findings represent the first functional evidence for the physiological role of cardiac M3 and M4 receptors.

4-Aminopyridine↗
PubMed1999

Occupational risk factors for sarcoma subtypes.

Herbicides, chlorophenols, and other occupational exposures are suspected risk factors for soft-tissue sarcoma, but the epidemiologic evidence is inconsistent. Given that soft-tissue sarcomas represent a heterogeneous mix of cancer subtypes and that these subtypes have different disease patterns by race, sex, and age at diagnosis, studying all soft-tissue sarcomas combined may mask subtype-specific associations. Using the Selected Cancers Study, a large population-based case-control study of sarcoma conducted among U.S. men aged 30 to 60 in 1984 to 1988, we explored the occupational risk factors for soft-tissue sarcoma subtypes and skeletal sarcoma. The analysis included 251 living sarcoma cases (48 dermatofibrosarcoma protuberans, 32 malignant fibrohistiocytic sarcoma, 67 leiomyosarcoma, 53 liposarcoma, and 51 skeletal sarcoma) and 1908 living controls. Exact conditional logistic regression models suggested patterns of subtype specificity for occupational exposures. Self-reported herbicide use was associated with malignant fibrohistiocytic sarcoma (OR = 2.9, 95% CI = 1.1-7.3). We found elevated risks for chlorophenol exposure and cutting oil exposure and malignant fibrohistiocytic sarcoma and leiomyosarcoma. We found no occupational risk factor for liposarcoma. Polytomous regression models identified different odds ratios across subtypes for plywood exposure and exposure to wood and saw dust. Although exploratory, this analysis suggests that occupational risk factors for sarcoma are not uniform across subtypes.

Adult↗
PubMed1998

[Subtype and sequence analysis of the C2-V3 region of gp120 genes among HIV-1 strains in Sichuan province].

Nine DNA fragments of HIV-1 env gene were amplified by PCR from uncultured peripheral blood mononuclear cells (PBMCs) obtained from HIV-1 sero-positive intravenous drug users (IDUs) in Sichuan province, in mid 1996. Their C2-V3 region (about 450 bp) was sequenced. Sequence analysis showed that there were two HIV-1 subtypes B and C, with 1.4% and 2.6% gene divergence inside each subtype, in Sichuan. The 5 subtype B strains, when comparing with sequences of several reference HIV-1 strains, were found similar to these identified in Thailand, Myanma and Yunnan province. The nucleotide sequence divergence between them was ranged from 3.6% to 4.3%. Meanwhile, the 4 subtype C strains except sc3, were most close to those found in India as well as in Yunnan province, and both their nucleotide sequence divergence was 3.1%. The sc3 strain belonged to subtype C but had larger genetic distance, between 10.1%-17.2%. Above results suggested a recent epidemic of both subtype HIV-1 strains in Sichuan provine and they were very close to those identified in Yunnan province: The subtype C strain of sc3 is special and its source remains not clear.

China↗
PubMedDate not supplied

HLA-B27 subtypes in patients with ankylosing spondylitis (As) in Colombia.

OBJECTIVE: We investigated the distribution of HLA-B27 subtypes in patients with ankylosing spondylitis (AS) belonging to two ethnic groups of Colombia. MATERIAL AND METHODS: PCR-SSOs was used to detect the polymorphism in exons 2 and 3 of HLA-B27 in two groups of patients: 39 Mulattos and 20 Mestizos. Fifty-nine of them suffered of ankylosing spondylitis (AS), including two patients with ankylosing spondylitis plus anterior uveitis (AU). Only two out of eight HLA-B27 subtypes studied (B*2701-B*2708) were found. RESULTS: The distribution of these alleles in the whole population was: B*2705: 87.1% and B*2702: 12.8% in the Mulattos group; 80% were B*2705 and 20% B*2702 in Mestizos group. The distribution of HLA-B27 subtypes was: 84.74% of patients with AS were B*2705 and 15.26% B*2702. CONCLUSIONS: There was no significant difference in the distribution of HLA-B27 subtypes among the patients ethnic groups studied. Other authors have shown that B*2705, B*2702 and B*2704, the more frequent subtypes, are equally associated to the disease. Although population studies need to be done to analyze the distribution of subtypes between patients and controls, the low frequency of HLA-B27 within the normal population does not permit to do a representative number of controls; our results suggest that HLA-B*2705 and HLA-B*2702 are the subtypes more frequently associated with AS in patients from the two more prevalent patients ethnic groups in Colombia.

Alleles↗
PubMed1975

Hepatitis B antigen, antigen subtypes, and hepatitis B antibody in normal subjects and patients with liver disease.

The relative sensitivities of counterimmunoelectrophoresis (CIE) and haemagglutination assays for the detection of hepatitis B surface antigen (HB(s)Ag) and antibodies (anti-HB(s)) were compared. Twelve scientists from ten countries in Asia, Africa and the Pacific region participated in the study. The participants provided serum samples from 15 953 subjects comprising patients with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), as well as blood donors and other normal individuals. For the detection of HB(s)Ag in a reference panel serum, immune adherence haemagglutination (IAHA) was slightly more sensitive than passive haemagglutination inhibition (PHI); CIE was the least sensitive. Mean HB(s)Ag frequencies in patients with acute hepatitis, chronic hepatitis, cirrhosis, and HCC were significantly higher than in healthy controls. Passive haemagglutination (PHA) was more sensitive than CIE for the detection of anti-HB(s). The frequency of anti-HB(s) in patients with HCC was significantly lower than that in the other groups. Mean anti-HB(s) frequencies in patients with acute hepatitis, chronic hepatitis, and cirrhosis were not significantly different from that in normal subjects. Subtyping of HB(s)Ag was performed by PHI. Among asymptomatic carriers the predominant HB(s)Ag subtype in northeast Asia was adr.In India, ayw predominated in carriers, with the demarcation between adr and ayw occurring west of Burma. In West Africa the only subtype detected was ayw, but in East Africa the majority subtype was adw. The r subtype was found only in Asian populations east of India and in Western Pacific populations. In Papua New Guinea all four subtypes were identified. With one possible exception, the subtypes of HB(s)Ag-positive patients with liver disease reflected the predominant type in each geographic location.

Africa↗
PubMed2001

[Relationship between respiratory syncytial virus subtype and clinical severity in bronchiolitis].

BACKGROUND: Respiratory syncytial virus (RSV) is the most frequently implicated agent in bronchiolitis. The virus presents two antigenic subtypes (A and B). The results of studies on the relationship between viral subtype and clinical severity are conflicting. PURPOSE: To evaluate whether the subtype of this virus constitutes an independent variable in the severity of clinical expression of RSV infection. PATIENTS AND METHODS: We prospectively studied previously healthy children aged less than 2 years admitted for RSV infection during an epidemic season. Clinical presentation and evolution, laboratory and radiological aspects were compared in subsets of children infected with RSV subtype A or B. Clinical severity parameters included score and duration of respiratory distress, oxygen requirements, admission to the intensive care unit, mechanical ventilation and length of hospital stay. RESULTS: Eighty-five patients were enrolled in the study (50 boys and 35 girls; mean age 4.8,4.3 months). Fifty-nine children were infected with RSV subtype A. No differences were found in age, sex or antecedents but children with subtype B were less likely to have been breast-fed. Clinical presentation and laboratory and radiological findings were similar in both groups. No statistically significant differences in clinical severity parameters were found between subsets A and B. Age less than 3 months was associated with greater duration of respiratory distress and longer hospital stay. CONCLUSION: The results do not support the hypothesis that subtype A infection is associated with more severe respiratory syncytial virus disease.

Bronchiolitis↗
PubMed1998

[Subtypes of the HLA-B27 molecule and association with spondylarthropathies].

HLA-B27 subtypes differ in their ethnic distribution and in their susceptibility to spondylarthropathies (SA). B*2705 and B*2702 are the most frequent disease-associated subtypes in Caucasians as well as B*2704 and B*2707 in Asia while B*2706 in Asia and B*2709 in Sardinia have been reported not to be associated to SA. Differences in antigenic peptide presentation could underlie such behavior. Several studies suggested that a Tyr C-terminal peptide anchor could be found preferentially in disease-associated subtypes and could be therefore one of the criteria in the search of putative arthritogenic peptide(s). We analyzed by HPLC and Edman sequencing peptides eluted from immunopurified HLA-B27 molecules expressed on B-lymphoblastoid cell lines or C1R transfectans of human origin. We focused our work on B*2707, associated with SA in the same geographical area where B*2706 is not. We found the same preference for Leu at the C-terminus in the peptides bound by both subtypes without any significant signal for Tyr. In the same experimental conditions a Tyr C-terminal anchor was found for B*2705, B*2702, B*2704, B*2703 and also for B*2701 and B*2708, 2 rare subtypes for which binding specificity was previously unknown. Comparison of the F-pocket aminoacid composition in these various subtypes showed a correlation between Asp at position 116 and Tyr at the peptide C-terminus. Asp116 is changed for Tyr in B*2706, B*2707 and His in B*2709, all subtypes allowing a Leu C-terminal anchor. Therefore a Tyr C-terminal anchor correlates with the HLA-B27 F-pocket composition rather than with susceptibility to SA.

Alleles↗
PubMed2001

Local anesthetics noncompetitively inhibit function of four distinct nicotinic acetylcholine receptor subtypes.

Local anesthetics (LAs) are considered to act primarily by inhibiting voltage-gated Na(+) channels. However, LAs also are pharmacologically active at other ion channels including nicotinic acetylcholine receptors (nAChR). nAChR exist as a family of diverse subtypes, each of which has a unique pharmacological profile. The current studies established effects of LAs on function of four human nAChR subtypes: naturally expressed muscle-type (alpha1*-nAChR) or autonomic (alpha3beta4*-nAChR) nAChR, or heterologously expressed nAChR containing alpha4 with either beta2- or beta4-subunits (alpha4beta2- or alpha4beta4-nAChR). Of the LAs tested, those with structures containing two separated aromatic rings (e.g., proadifen and adiphenine) had the greatest inhibition potency (IC(50) values between 0.34 and 6.3 microM) but lowest selectivity (approximately 4-fold) across the four nAChR subtypes examined. From the fused, two-ring (isoquinoline backbone) class of LAs, dimethisoquin had comparatively moderate inhibition potency (IC(50) values between 2.4 and 61 microM) and approximately 30-fold selectivity across nAChR subtypes. Lidocaine, a commonly used LA from the single ring category of LAs, blocked nAChR function with IC(50) values of between 52 and 250 microM and had only approximately 5-fold selectivity across nAChR subtypes. Its quaternary triethyl ammonium analog, QX-314, had greater inhibition potency, but the trimethyl ammonium derivative, QX-222, was the least potent LA at all but the alpha4beta2-nAChR subtype. With only a few exceptions, LA effects were consistent with noncompetitive inhibition of nAChR function and occurred at therapeutic doses. These studies suggest structural determinants for LA action at diverse nAChR subtypes and that nAChR likely are clinically relevant targets of LAs.

Anesthetics, Local↗
PubMed2000

Expression of alpha1 adrenoceptor subtypes mRNA in hepatic tissues of cirrhotic patients with portal hypertension.

OBJECTIVE: To investigate the expression of mRNA of alpha(1) adrenoceptor in the hepatic tissues of cirrhotic patients with portal hypertension. METHODS: Semi-quantitative reverse transcription and polymerase chain reaction (RT-PCR) was used in 12 hepatitis virus B-related cirrhotic patients with portal hypertension and 15 controls who had no history of portal hypertension. In these patients, routine liver biopsy was performed. Special alpha(1) adrenoceptor subtype product and internal standard GAPDH product were both amplified by RT-PCR. The ratio of their integral optical density (IOD) was calculated as the relative expression of the alpha(1) adrenoceptor subtypes. RESULTS: The relative mRNA expression of alpha(1a) adrenoceptor subtype in the hepatic tissues was significantly lower in the cirrhotic patients (0.26 +/- 0.12) than in the controls (0.86 +/- 0.38, P < 0.01). The relative mRNA expression of alpha(1b) adrenoceptor subtype in the hepatic tissues was also significantly lower in the cirrhotic patients (0.03 +/- 0.01) than in the controls (0.23 +/- 0.10, P < 0.01). Neither the cirrhotic patients nor the controls showed alpha(1d) adrenoceptor subtype in the hepatic tissues. The relative mRNA expression of alpha(1a) adrenoceptor subtype was significantly higher than that of alpha(1b) adrenoceptor subtype in the hepatic tissues of both cirrhotic patients and controls (P < 0.01). CONCLUSIONS: The alpha(1a) adrenoceptor mRNA expression predominates in both normal and cirrhotic hepatic tissues. The expression of alpha(1b) adrenoceptor is less marked and there is no expression of alpha(1d) adrenoceptor. The decreased expression of mRNA of alpha(1a) and alpha(1b) adrenoceptor may underlie the decrease of alpha(1) adrenoceptor proteins often seen in the hepatic tissues of cirrhotic patients, and may play an important role in the pathogenesis and maintenance of portal hypertension.

Adult↗
PubMedDate not supplied

Molecular subtyping methods for Listeria monocytogenes.

Conventional, phenotypic, and DNA-based subtyping methods allow differentiation of Listeria monocytogenes beyond the species and subspecies level. Bacterial subtyping methods not only improve our ability to detect and track human listeriosis outbreaks, but also provide tools to track sources of L. monocytogenes contamination throughout the food system. The use of subtyping methods also provides an opportunity to better understand the population genetics, epidemiology, and ecology of L. monocytogenes. The last 5 years have seen tremendous advancements in the development of sensitive, rapid, automated, and increasingly easy-to-use molecular subtyping methods for L. monocytogenes. This review highlights key aspects of different L. monocytogenes subtyping methods and provides examples of their application in public health, food safety, population genetics, and epidemiology. A significant focus is on the application of subtyping methods to define L. monocytogenes subtypes and clonal groups, which may differ in phenotypic characteristics and pathogenic potential.

Bacterial Typing Techniques↗
PubMed1976

Hepatitis B-antigen subtypes in Australia as detected by radioimmunoassay.

The distribution of the major subtypes of hepatitis B surface antigen (HBsAg) was examined in asymptomatic white Australian blood donors and patients with liver disease to attempt ot assess the biological significance of these subtypes in this relatively homogeneous Caucasian population. Since previous studies have shown a very low prevalence of HBsAg in white Australians, a highly sensitive solid phase radioimmunoassay (RIA) was developed and used to subtype the antigen. A total of 46 samples of hepatitis B-antigen positive sera, obtained from 21 asymptomatic volunteer blood donors and 25 patients with liver disease, were tested. Sixteen of these 21 asymptomatic carriers were shown to have subtype "ad" whereas only seven of the patients with liver disease had this subtype. This difference was significant (P less than 0.005) and supports the view that subtype "ad" is associated with a carrier state and subtype "ay" with liver disease in Australia.

Acute Disease↗
PubMed1992

Beta 1- and beta 2-adrenergic receptors display subtype-selective coupling to Gs.

beta-Adrenergic receptor (beta AR) subtypes differ in their affinities for some agonists and antagonists and thus may potentially impart different cellular effects based on this ligand-binding specificity. However, the possibility that there may be subtype-specific events subsequent to ligand binding has not been evaluated extensively. In particular, although beta ARs stimulate adenylyl cyclase by coupling to the guanine nucleotide-binding protein Gs, no studies have directly assessed the coupling efficiencies among isolated beta AR subtypes. We, therefore, permanently transfected the mammalian fibroblast cell line CHW-1102 with beta 1- or beta 2AR cDNAs and studied the coupling characteristics of these two receptor subtypes, each expressed at approximately 335 fmol/mg of protein. Both receptors mediated equivalent maximal increases in adenylyl cyclase activities (6.63 +/- 1.85-fold for beta 1AR versus 6.10 +/- 0.53-fold for beta 2AR; p = not significant). However, the isoproterenol dose-response curves for the beta 2AR were shifted to the left, compared with those for the beta 1AR (EC50 of 52.3 +/- 2.87 nM and 191 +/- 10.5 nM, respectively; p less than 0.05), resulting in an approximately 4-fold greater potency for the beta 2AR versus the beta 1AR. Thus, at the submaximal isoproterenol concentration of 30 nM, the beta 2AR stimulated adenylyl cyclase approximately 50% more than did the beta 1AR. This finding was not due to a difference in the affinities of isoproterenol for these receptors, which were found to be the same, as determined by competition binding studies with 125I-cyanopindolol in the presence of GTP. The ability of beta 1- and beta 2ARs to form the high affinity ternary complex was assessed in agonist competition studies without guanine nucleotide. We found that, whereas the proportion of receptors in the high affinity state was equivalent between the two receptor subtypes, the affinity of this state for isoproterenol was approximately 5-fold greater for the beta 2AR, compared with the beta 1AR (KH for beta 2AR, 11.8 +/- 3.1 nM; KH for beta 1AR, 61.7 +/- 18.3 nM; p less than 0.05). In addition, we examined physical and functional coupling of beta 1- and beta 2ARs to Gs using the agonist epinephrine, which also has equal binding affinity for both receptor subtypes. As with isoproterenol, epinephrine was more potent in stimulating adenylyl cyclase and promoted a higher affinity ternary complex for the beta 2AR. Thus, a greater degree of both physical and functional agonist-promoted coupling occurs between Gs and beta 2AR, compared with beta 1AR. We conclude that coupling to Gs by beta 1- and beta 2ARs is subtype selective and is a potentially important distinguishing feature among these members of the beta AR family.

Adrenergic beta-Agonists↗