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 451 records · Page 25Linked to original sources
PubMed2006

The relationship between homocysteine, cognition and stroke subtypes in acute stroke.

BACKGROUND: Elevations in plasma homocysteine (Hcy) have been associated with an increased risk of stroke and dementia. The mechanisms underlying these associations remain poorly understood. OBJECTIVES: This study examines the relationships between Hcy, cognition, and stroke subtype. We hypothesize that: 1) Hcy levels are inversely related to cognition, 2) Hcy levels are unrelated to stroke subtype, and 3) stroke subtype affects cognition. METHODS: We studied 169 consenting patients admitted for acute stroke during a 4 month period. Blood was drawn for Hcy levels and the Mini-Mental State Examination (MMSE) was administered within 9 days of admission. The Oxfordshire Community Stroke Project Classification was used to characterize stroke subtypes. Correlation between Hcy and MMSE scores was examined as was the relationships between Hcy and stroke subtype, and between stroke subtypes and MMSE scores. RESULTS: A significant inverse correlation between Hcy levels and MMSE scores was demonstrated (r=-0.243, p=0.001). MMSE scores also differed according to the type of stroke, with Total or Partial Anterior Circulation Infarcts (TACI/PACI) scoring lowest (F=8.77, df=2, p<0.001). Hcy levels did not differ between the various stroke subtypes (F=0.21, df=2, p=0.81). Multivariate linear regression analysis showed that age, education, and stroke subtype, but not Hcy, were independent predictors of acute MMSE scores. CONCLUSIONS: In this study sample, there was an inverse relationship between Hcy and cognition in acute stroke patients. However, Hcy was not an independent predictor for cognition in acute stroke after other factors such as stroke subtype and patient age were taken into account. These results suggest that during the acute stage of stroke, stroke subtype is a more important factor in determining cognition than Hcy levels.

Acute Disease↗
PubMed2004

Subtyping female adolescent psychiatric inpatients with features of eating disorders along dietary restraint and negative affect dimensions.

Cluster-analytic studies of eating disorders in adult patients have yielded two subtypes (pure dietary and mixed dietary-negative affect). This study aimed to replicate the subtyping in female adolescent psychiatric inpatients with features of eating disorders. Cluster analyses of 137 patients with eating-disordered features revealed a dietary-negative affect subtype (43%) and a pure dietary subtype (57%). The dietary-negative affect subtype was characterized by greater likelihood of binge eating, greater eating-related psychopathology, and greater body image dissatisfaction. The two subtypes did not differ significantly in scores reflective of clinical syndromes (other than the significantly higher depressive affect in the negative affect subtype), but the dietary-negative affect subtype was characterized by greater personality disturbance and higher reported concerns in clinical areas, including suicidality and childhood abuse. The cluster analysis produced different results from an alternative approach to subtyping by vomiting. These findings provide further support for the reliability and validity of this subtyping scheme for eating pathology. Clinically, the findings suggest that the combination of dieting and negative affect signals a more disturbed variant of eating-disorder related psychopathology in female adolescent psychiatric inpatients.

Adolescent↗
PubMed2002

Affinity profile at alpha(1)- and alpha(2)-adrenoceptor subtypes and in vitro cardiovascular actions of (+)-boldine.

The present study examines the functional and binding affinities of the aporphine alkaloid, (+)-boldine, at different alpha(1)- and alpha(2)-adrenoceptor subtypes, namely, alpha(1A) (rat vas deferens and kidney) and its L-like state (rabbit spleen), alpha(1B) (guinea pig spleen, mouse spleen and rabbit aorta), alpha(1D) (rat aorta and pulmonary artery), at possible subtypes of prejunctional alpha(2)-adrenoceptors in rat and rabbit vas deferens and rat atrium, alpha(2D) in guinea pig ileum, cloned human alpha(1)-adrenoceptor subtypes A, B and D and alpha(2)-adrenoceptor subtypes A, B and C as well as rat alpha(2D)-adrenoceptors. Additionally, we investigated its Ca(2+) channel antagonism in vascular and cardiac preparations. (+)-Boldine had higher affinity at alpha(1)-adrenoceptor subtype A (pA(2)=7.46, pK(i)=7.21) compared with its L-like state (pA(2)=5.63) or subtype B (pA(2)=5.98- 6.12, pK(i)=5.79) and subtype D (pA(2)=6.18-6.37, pK(i)=6.09). Its affinities at alpha(2)-adrenoceptors in rat and rabbit vas deferens and rat atrium (pA(2)=6.02, 6.36, 6.06, respectively) were identical, but lower at guinea pig ileum alpha(2D)-adrenoceptors (pA(2)=4.38). (+)-Boldine displayed nearly undistinguishable affinity at cloned human alpha(2)-adrenoceptor subtypes A, B and C (pK(i)=6.26, 5.79 and 6.35, respectively), whereas its affinity at rat alpha(2D)-adrenoceptors was low (pK(i)=4.70). In perfused rat kidney, (+)-boldine inhibited K(+)-evoked vasoconstriction at doses 70-fold higher than diltiazem. In guinea pig Langendorff heart, (+)-boldine (10(-5) - 2 x 10(-4) M) was equieffective in increasing coronary flow and in depressing cardiac force, while lower concentrations already depressed heart rate. In papillary muscles from guinea pig, (+)-boldine (10(-6) - 10(-5) M) mainly prolonged the duration of action potential at levels >30% of repolarization. These data reveal that (+)-boldine, except for its moderate selectivity (15 to 25-fold) for alpha(1A)-adrenoceptors, does not discriminate between the alpha(1)-adrenoceptor subtypes B and D and alpha(2)-adrenoceptor subtypes A, B and C, at which the drug consistently displays micromolar affinity. In vascular and cardiac preparations, (+)-boldine, although being at least 50-fold weaker than diltiazem, shows Ca(2+) channel antagonistic properties but no specificity for coronary dilatation relative to cardiodepression.

Animals↗
PubMed1990

Variation in severity of respiratory syncytial virus infections with subtype.

Two major subtypes of respiratory syncytial virus have been identified. This study assessed the hypothesis that A-subtype infections were more severe than B-subtype infections among the 157 infants hospitalized in two hospitals in Rochester, N.Y., during two winters. Severity was measured both by specific clinical observations and by a severity index that was derived empirically. Among all subjects, several clinical observations suggested that A-subtype infections were more severe. For example, mechanical ventilation was required in 12.6% of those with A-subtype compared with 1.6% of those with B-subtype infection (relative risk = 7.88; p = 0.01). Among high-risk infants (infants with underlying conditions or age 3 months or less at admission), carbon dioxide tension greater than 45 mm Hg was found in 37.0% of those with A-subtype compared with 12.0% of those with B-subtype infection (relative risk = 3.08; p = 0.04). In discrete multivariate (logit) analysis, effects of subtype (odds ratio = 6.59; p less than 0.01) on severity remained after adjustment for other statistically significant effects of age less than 3 months, underlying condition, and premature birth. The finding that A-subtype infections were more severe might have important implications for vaccine development, studies of the virulence of respiratory syncytial virus, clinical management (e.g., selection for antiviral therapy), and long-term prognosis.

Age Factors↗
PubMed1998

In vitro autoradiography of GTPgamma[35S] binding at activated NPY receptor subtypes in adult rat brain.

Guanylyl 5'-[gamma[35S]thio]-triphosphate (GTPgamma[35S]) binding to NPY receptor-activated G-proteins was measured in adult rat brain sections in order to determine the neuroanatomical distribution of NPY receptor subtypes. Using the pharmacological specificity of the NPY receptor subtypes, differential stimulation of GTPgamma[] binding by subtype-specific agonists was used to demonstrate the differential distribution of these subtypes in rat brain. Treatment of rat brain slices with selective agonists for the NPY receptor subtypes in the presence of 2000 microM GDP was used to discriminate populations of NPY receptor subtypes. Activation of a NPY Y1 receptor subtype by human [Leu31Pro34]NPY stimulated GTPgamma[35S] binding in the rank order: frontal cortex>dentate gyrus>inferior colliculus>/=thalamus>hypothalamus. In contrast, NPY Y2/Y5 peptide agonist, human PYY(3-36), stimulated GTPgamma[35S] binding in the rank order: hypothalamus>substantia nigra>hippocampus>frontal cortex>/=inferior colliculus. Stimulation of NPY Y5 receptor subtypes by a NPY Y5 selective agonist, rat/human D-Trp, was shown to stimulate GTPgamma[35S] binding in the hypothalamus and discrete nuclei of the thalamus. Little GTPgamma[35S] binding in the dentate gyrus, frontal cortex, or inferior colliculus was measured following stimulation with D-Trp. Stimulation of GTPgamma[35S] binding by [Leu31Pro34]NPY, but not by the other NPY receptor agonists, was blocked by the selective NPY Y1 receptor antagonist, BIBP 3226. In conclusion, functional coupling at NPY receptor subtypes can be shown in rat brain and populations of NPY receptor subtypes can be anatomically discriminated by NPY agonist stimulation of GTPgamma[35S] binding in rat brain.

Animals↗
PubMed1997

Alpha 2-adrenergic receptor subtypes in rat dorsal root and superior cervical ganglion neurons.

To determine which alpha 2-adrenergic receptor subtypes are present in primary afferent and sympathetic postganglionic neurons we have performed in situ hybridization and immunohistochemistry experiments on rat dorsal root and superior cervical ganglia. Reverse transcriptase polymerase chain reaction was used as a preliminary screen for the presence of mRNA encoding alpha 2-adrenergic subtypes in dorsal root and superior cervical ganglia; polymerase chain reaction primers amplified distinct regions of the rat alpha 2A-(RG20), alpha 2B-(RNG) and alpha 2C-(RG10) adrenergic receptor subtypes in mRNA extracted from lumbar dorsal root and superior cervical ganglia. To localize receptors to cell types in the ganglia, in situ hybridization was performed on cryosections of dorsal root and superior cervical ganglia with oligonucleotide probes designed to distinguish between mRNA encoding for alpha 2-adrenergic receptor subtypes. Immunohistochemistry was performed with a polyclonal antibody against the alpha 2A-adrenergic receptor subtype. Our results with reverse transcriptase polymerase chain reaction indicate that all three alpha 2-adrenergic receptor subtypes are expressed in dorsal root and superior cervical ganglia. Data from the in situ hybridization experiments indicated that the mRNA detected with the reverse transcriptase polymerase chain reaction was present in neuronal cell bodies, except for the mRNA encoding the alpha 2A-adrenergic receptor which was not detectable in dorsal root ganglia. The distribution of mRNA encoding alpha 2B- and alpha 2C-adrenergic receptor subtypes among dorsal root ganglion neurons and alpha 2A-, alpha 2B- and alpha 2C-adrenergic receptor subtypes among superior cervical ganglion neurons suggests that multiple adrenergic receptor subtypes are present in a single neuron. Neuronal cell bodies in both the dorsal root and superior cervical ganglion consistently demonstrated alpha 2A-adrenergic receptor-like immunoreactivity. The apparent co-expression of multiple alpha 2-adrenergic receptor subtypes in dorsal root and superior cervical ganglion neurons enables a single transmitter to produce a number of effects in the same neuron; which receptors are functionally active may vary with the presence of nerve injury, inflammation or other physiological and pathophysiological conditions.

Animals↗
PubMed1999

Genetic subtyping of Escherichia coli O157 isolates from 41 Pacific Northwest USA cattle farms.

Escherichia coli O157 (n = 376) from 41 cattle farms were subtyped using pulsed field gel electrophoresis of endonuclease cleaved chromosomal DNA. Cleavage with XbaI resulted in 81 subtypes. Fifty-one isolates from subtypes found in more than one herd, or in herds on multiple sample collection dates were compared using the endonuclease NotI, resulting in 23 additional subtypes. Up to 11 XbaI subtypes were found per farm with up to 7 subtypes/farm identified from a single date. Indistinguishable subtypes (both XbaI and NotI) were found to persist on 4 farms for 6-24 months. Five subtypes were found on more than one farm separated by up to 640 km. Dairy farms where cattle had moved onto the farm had a similar number of subtypes as farms with no movement of cattle, and feedlots had more subtypes than dairy farms. These data indicate that there is a mechanism for multiple herd exposure to specific subtypes, there are multiple sources of exposure for cattle on farms, and on-farm reservoirs other than cattle may exist.

Animals↗
PubMed1991

Functional interactions of recombinant alpha 2 adrenergic receptor subtypes and G proteins in reconstituted phospholipid vesicles.

The functional interaction of the recombinant alpha 2 adrenergic receptor subtypes, alpha 2-C10 (the human platelet alpha 2 receptor, equivalent to the alpha 2 A subtype) and alpha 2-C4 (an alpha 2 receptor subtype cloned from a human kidney cDNA library), with G proteins was characterized in an in vitro reconstitution system. These receptor subtypes were overexpressed in COS-7 cells and were purified to a specific activity of 1.1-3.3 nmol/mg of protein. The G proteins consisted of Gs (adenylyl cyclase stimulatory) and members of the inhibitory family, including Gi1, Gi2, and Gi3, and G0. The cloned alpha subunits of these G proteins were overexpressed in Escherichia coli and were purified to homogeneity. Prior to use, G holoproteins were prepared by mixing the alpha subunits with beta gamma subunits that had been purified from bovine brain. Following reconstitution into phospholipid vesicles, both alpha 2 receptor subtypes could couple to the inhibitory G proteins but not to Gs, as assessed by agonist stimulation of GTPase activity. The pharmacological specificity of this interaction was preserved with respect to the two receptor subtypes. Between the different inhibitory G proteins, the alpha 2-C10 adrenergic receptor subtype showed the following preference: Gi3 greater than Gi1 greater than or equal to Gi2 greater than G0. The stimulation of GTPase activity (turnover number) ranged from 6.4-fold (Gi3) to 1.5-fold (G0). The preference of G-protein interaction for the alpha 2-C4 receptor subtype was the same as that observed for the alpha 2-C10, but the extent of activation was slightly lower. The results show that in vitro each of the alpha 2 adrenergic receptor subtypes can activate multiple G proteins but that clear preferences exist with respect to the individual inhibitory G-protein subtypes. Additionally, it appears that alpha 2-C10 is coupled more efficiently to G-protein activation than is alpha 2-C4.

Animals↗
PubMed1994

A new approach to the design of sigma-2-selective ligands: synthesis and evaluation of N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1- pyrrolidinyl)ethylamine-related polyamines at sigma-1 and sigma-2 receptor subtypes.

A series of polyamines based on the high affinity sigma receptor ligand N-[2-(3,4-dichlorophenyl)-ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) were developed and evaluated for their binding characteristics at sigma-1 and sigma-2 receptor subtypes. The data indicated that a considerable degree of structural variation is possible while still retaining nanomolar affinity at sigma receptors. As the structure of the polyamines was varied, their binding at sigma-1 and sigma-2 subtypes showed quite different and in some cases opposite trends, supporting the belief that these are pharmacologically distinct entities. Polyamines containing two nitrogen atoms showed optimal binding at both sigma-1 and sigma-2 receptor subtypes. Although additional nitrogen atoms resulted in decreased affinity at sigma-1 and sigma-2 subtypes, an increase in selectivity for sigma-2 subtypes was evident; the parent 3 showed greater selectivity for sigma-1 subtypes. Internitrogen spacings had a large effect on binding affinity and subtype selectivity. For example, the difference between N-[3-(1-pyrrolidinyl)propyl]-N'-(3,4-dichlorobenzyl)-N,N'- dimethylethylenediamine (8) [K(i) = 29.9 nM at sigma-1 receptor and 18.3 nM at sigma-2 receptor] to N-[3-(1-pyrrolidinyl)propyl]-N'-(3,4-dichlorobenzyl)- N,N'-dimethylethylenediamine (10) [K(i) = 1.49 nM at sigma-1 receptor and 12.1 nM at sigma-2 receptor] illustrates the importance of internitrogen spacing. Triamines 11 and 13 [Ki(sigma-2)/K(i)(sigma-1) = 0.19 and 0.10, respectively] containing the N-N-N-Ar spacings 3-3-2 and 4-4-2, proved to be the most sigma-2 subtype selective of the 15 polyamines examined in this study. The N-N-N spacings appear to be an important factor in their sigma-2 subtype selectivity. These compounds will serve as templates in the design of still further sigma-2 subtype selective ligands. The pyrrolidine ring (present in most of the polyamines tested in this series) proved to be an important recognition site for sigma receptor binding activity. Furthermore, alkyl substitution also appears to be important since the stripped down polyamines N-[2-(3,4-dichlorophenyl)ethyl]ethylenediamine (15) and N1-[2-(3,4-dichlorophenyl)ethyl]diethylenetriamine (16) exhibited relatively low binding affinity.

Animals↗
PubMed2001

Somatostatin enhances cAMP-dependent short-circuit current in human colon via somatostatin receptor subtype-2.

Somatostatin inhibits colonic ion secretion in animal models and cultured intestinal cell lines via somatostatin receptor subtype 2 and subtype 1, respectively. In a recent in vitro ion transport study of the human colon, somatostatin was shown to stimulate short-circuit current, a measure of electrogenic ion transport. In this study we have used the reverse-transcription polymerase chain reaction (RT-PCR) and measurements of changes in short-circuit current (Isc) in response to receptor subtype-specific analogs of somatostatin, to define the somatostatin receptor subtype responsible for the stimulation of short-circuit current in human colon. Somatostatin receptor subtypes 1, 2, and 5, but not 3 and 4, were detected in the human colonic epithelium. Measurements of short-circuit current showed somatostatin and octreotide (1 micromol/liter) increased the prostaglandin stimulated short-circuit current by 12.3+/-1 and 11.0+/-1 microA/cm2, respectively. Similarly, analogs selective for somatostatin receptor subtypes 2 and 5 (1 micromol/liter) produced an increase of short-circuit current of 11.7+/-1 and 13.2+/-1 microA/cm2, respectively. However, at a concentration (10 nmol/liter) near the EC50, the somatostatin receptor subtype 2 analog increased short-circuit current by 9+/-1 microA/cm2, whereas the receptor subtype 5 analog had no effect. There was no difference in receptor expression or effect of the peptides related to the anatomical site of tissue collection. In conclusion, human colonic mucosa expresses multiple somatostatin receptor subtypes, of which subtype 2 mediates the stimulatory effect of somatostatin on ion transport.

Colon↗
PubMed2001

Subtyping binge eating disorder.

Cluster-analytic studies of bulimia nervosa and binge eating disorder (BED) have yielded 2 subtypes (pure dietary and mixed dietary-negative affect). The authors aimed to (a) replicate the subtyping with BED, (b) consider alternative approaches to subtyping, and (c) test the stability in individual differences in the subtyping. Cluster analyses of 101 patients revealed a dietary-negative affect subtype (33%) and a pure dietary subtype (67%). The dietary-negative affect subtype was characterized by greater eating-related psychopathology and psychological disturbance. Cluster analysis produced different results from alternative subtyping approaches (by major depression or by binge eating frequency). Cluster-analytic subtyping of data at 2 time points 4 weeks apart for a subset of 73 patients demonstrated significant consistency (kappa = .55). Findings suggest that moderate dieting is characteristic of BED and that affective disturbances occur in a subset of cases that represent a more disturbed variant. The subtypes may represent reasonably stable individual differences.

Adult↗
PubMed1994

Prognostic significance of histopathological subtypes in stage I pure yolk sac tumour of the ovary.

The correlation between histological subtype [endodermal sinus (ES), polyvesicular vitelline (PV), glandular (G) and hepatoid (H) subtypes] and the prognosis of pure yolk sac tumours (YSTs) of the ovary was investigated. From 1964 to 1989, 35 patients with YSTs were treated with primary surgery and adjuvant chemotherapy. The prevalence of histological subtypes was as follows: 14 patients had a single subtype, either ES (12) or G (2); 12 patients had two subtypes, ES+G (4), ES+PV (3), ES+H (4) or G+H (1); six patients had three subtypes, ES+P+H (4) or ES+G+H (2); and three patients had all four subtypes. Multivariate analysis showed that important predictors were FIGO stage, chemotherapeutic regimen and residual tumour size. However, for stage I, multivariate analysis showed that the histological subtype was a superior predictor to the subclassification of FIGO stage I, age or chemotherapeutic regimen (P = 0.03). Kaplan-Meier analysis showed that YSTs composed of an admixture of three or four subtypes was associated with a better prognosis than those composed of one or two subtypes (P < 0.01), other variables being constant.

Adolescent↗
PubMed2003

Methyridine (2-[2-methoxyethyl]-pyridine]) and levamisole activate different ACh receptor subtypes in nematode parasites: a new lead for levamisole-resistance.

1. The development of resistance to all chemotherapeutic agents increases and needs to be addressed. We are interested in resistance in parasitic nematodes to the anthelmintic levamisole. During studies on methyridine, we found that it gave us a new insight into pharmacological changes associated with levamisole resistance. Initially, electrophysiological investigation using a two-micropipette current-clamp recording technique revealed that methyridine acts as a cholinergic agonist on nematode muscle receptors (Ascaris suum). Methyridine (>30 microm) produced reversible concentration-dependent depolarizations and increases in input conductance. Mecamylamine (30 microm) and paraherquamide (0.3 microm) produced reversible antagonism of the depolarization and conductance responses to methyridine. These observations suggest that methyridine, like acetylcholine and levamisole, gates ion channels on the muscle of parasitic nematodes. 2. The antagonistic effects of dihydro-beta-erythroidine and paraherquamide on methyridine-induced contractions of A. suum muscle flaps were then examined to determine if methyridine showed subtype selectivity for N-subtype (nicotine-sensitive) or L-subtype (levamisole-sensitive) acetylcholine receptors. Dihydro-beta-erythroidine weakly antagonized the effects of methyridine (but had no effect on levamisole responses). The antagonism of methyridine (pA2, 5.9) and nicotine (pA2, 6.1) by paraherquamide was similar, but was less than the antagonism of levamisole (pA2, 7.0). The antagonist profiles suggested that methyridine has a selective action on the N-subtype rather than on the L-subtype. 3. A novel use for a larval inhibition migration assay was made using L3 larvae of Oesophagostomum dentatum. Inhibitory effects of nicotine, levamisole, pyrantel and methyridine on the migration of larvae of levamisole-sensitive (SENS) and levamisole-resistant (LEV-R) isolates were tested at different concentrations. Levamisole and pyrantel (putative L-subtype-selective agonists) concentration-response plots were displaced to the right in LEV-R isolates. Nicotine (an N-subtype-selective agonist) and methyridine produced little shift in concentration-response plots in the LEV-R isolates. Resistance dose ratios were used to calculate the relative selectivity, rhoL, for the L-type receptor (levamisole rhoL=1.0; pyrantel rhoL=0.93; methyridine rhoL=0.17; nicotine rhoL=0.06). These observations reveal an N-subtype-selective action of methyridine and suggest that levamisole resistance may be associated with a loss of the L-subtype, but not the N-subtype receptors. The pharmacology of methyridine suggests an approach for the treatment of levamisole-resistant parasites.

Animals↗
PubMed1999

Distribution of alpha1-adrenoceptor subtype mRNAs in human renal cortex.

OBJECTIVE: To determine the quantity and distribution of alpha1-adrenoceptor subtype mRNAs in human renal cortex. MATERIALS AND METHODS: Specimens of renal cortex tissue were obtained at the time of radical nephrectomy or total nephroureterectomy from 46 patients (mean age 59.0 years, sd 14.7) with renal cell carcinoma, renal pelvic or ureteric tumour. Using the reverse-transcriptase polymerase chain reaction (RT-PCR), the RNase protection assay and in situ hybridization, the presentation, quantity and distribution of alpha1-adrenoceptor subtype mRNAs were determined. RESULTS: Expression of the three alpha1-adrenoceptor subtype mRNAs (alpha1a, alpha1b and alpha1d) was confirmed in the arteries of the renal cortex (arciform, interlobular, arteriole), but among the three subtypes, the alpha1b was less apparent by in situ hybridization. Intense alpha1-mRNA staining was apparent especially in the smooth muscle of arterial walls. In both proximal and distal renal tubules, each of the alpha1-mRNAs was less marked in cytoplasm than in the arteries. In the glomeruli weak staining was detected in the endothelium but there was no obvious staining in the veins. RT-PCR showed all three subtypes of alpha1-adrenoceptor. The RNase protection assay showed that the predominant alpha1-adrenoceptor subtype mRNA in human renal cortex was alpha1a. However, the abundance of alpha1a-mRNA in human kidney was much less than in the prostate. CONCLUSION: Three alpha1-adrenoceptor subtype mRNAs were recognized in human renal cortex and detected particularly in the smooth muscle of the arteries. There was more alpha1a-adrenoceptor subtype in human renal cortex than the other subtypes. It is not known how each subtype operates against adrenergic stimulation; further studies are needed to examine receptor density or receptor function.

Adult↗
PubMed1997

The second intracellular loop of the alpha2-adrenergic receptors determines subtype-specific coupling to cAMP production.

The alpha2-adrenergic receptors (alpha2-ARs), which primarily couple to inhibition of cAMP production, have been reported to have a stimulating effect on adenylyl cyclase activity in certain cases. When expressed in Spodoptera frugiperda Sf9 cells the alpha2A subtype showed only inhibition of forskolin-stimulated cAMP production when activated by norepinephrine (NE), whereas the alpha2B subtype displayed a biphasic dose-response curve with inhibition at low concentrations of NE and a potentiation at higher concentrations. To further investigate the subtype-specific coupling, we expressed a set of chimeric alpha2A-/alpha2B-ARs at similar expression levels in Sf9 cells to determine the structural domain responsible for the difference between the two subtypes. When the third intracellular loops were interchanged between alpha2A and alpha2B subtypes, the coupling specificity remained unchanged, indicating that this loop does not confer selectivity toward a stimulating response. A biphasic dose-response curve, typical for the alpha2B subtype, could be seen when the second intracellular loop of the alpha2B subtype was inserted into the alpha2A subtype, suggesting that this loop is important for determining the subtype-specific coupling of alpha2-ARs to cAMP production. Site-directed mutagenesis of non-conserved amino acids in the second intracellular loop of the alpha2A subtype indicated that several residues are involved in the coupling specificity.

Adenylate Cyclase Toxin↗
PubMed2000

Constitutively active mutants of the alpha(1a)- and the alpha(1b)-adrenergic receptor subtypes reveal coupling to different signaling pathways and physiological responses in rat cardiac myocytes.

Activation of alpha(1)-adrenergic receptors influences both the contractile activity and the growth potential of cardiac myocytes. However, the signaling pathways linking activation of specific alpha(1)-adrenergic receptor (AR) subtypes to these physiological responses remain controversial. In the present study, a molecular approach was used to identify conclusively the signaling pathways activated in response to the individual alpha(1A)- and alpha(1B)-AR subtypes in cardiac myocytes. For this purpose, a mutant alpha(1a)-AR subtype (alpha(1a)-S(290/293)-AR) was constructed based on analogy to the previously described constitutively active mutant alpha(1b)-AR subtype (alpha(1b)-S(288-294)-AR). The mutant alpha(1a)-S(290/293)-AR subtype displayed constitutive activity based on four criteria. To introduce the constitutively active alpha(1)-AR subtypes into cardiac myocytes, recombinant Sindbis viruses encoding either the alpha(1a)-S(290/293)-AR or alpha(1b)-S(288-294)-AR subtype were used to infect the whole cell population with >90% efficiency, thereby allowing the biochemical activities of the various signaling pathways to be measured. When expressed at comparable levels, the alpha(1a)-S(290/293)-AR subtype exhibited a significantly elevated basal level as well as agonist-stimulated level of inositol phosphate accumulation, coincident with activation of atrial natriuretic factor-luciferase gene expression. By contrast, the alpha(1b)-S(288-294)-AR subtype displayed a markedly increased serum response element-luciferase gene expression but no activation of atrial natriuretic factor-luciferase gene expression. Taken together, this study provides the first molecular evidence for coupling of the alpha(1a)-AR and the alpha(1b)-AR subtypes to different signaling pathways in cardiac myocytes.

Adrenergic alpha-Agonists↗
PubMed2001

Impact of human immunodeficiency virus type 1 (hiv-1) subtype on women receiving single-dose nevirapine prophylaxis to prevent hiv-1 vertical transmission (hiv network for prevention trials 012 study).

In Uganda, the HIV Network for Prevention Trials (HIVNET) 012 study recently demonstrated that single-dose nevirapine (Nvp) prophylaxis is effective for preventing mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1). This exploratory study examines the relationship between HIV-1 subtype, MTCT, and the development of Nvp resistance (Nvp(R)) in women enrolled in HIVNET 012. For 102 women (32 whose infants were HIV-1 infected by age 6-8 weeks and 70 whose infants were uninfected), HIV-1 subtypes included 50 (49%) subtype A, 35 (34%) subtype D, 4 (4%) subtype C, 12 (12%) recombinant subtype, and 1 unclassified. There was no apparent difference in the rate of MTCT among women with subtype A versus D (adjusted odds ratio [OR], 1.24; 95% confidence interval [CI], 0.45-3.43). Nvp(R) mutations were detected more frequently at 6-8 weeks postpartum in women with subtype D than in women with subtype A (adjusted OR, 4.94; 95% CI, 1.21-20.22). Additional studies are needed to further define the relationship between HIV-1 subtype and Nvp(R) among women receiving Nvp prophylaxis.

Anti-HIV Agents↗
PubMed2000

Genetic characterization of incident HIV type 1 subtype E and B strains from a prospective cohort of injecting drug users in Bangkok, Thailand.

We obtained specimens from 128 HIV-1 seroconverters identified from 1995 through 1998 in a prospective cohort study of 1,209 HIV-negative injecting drug users (IDUs) in Bangkok, Thailand. Epidemiologic data indicated that parenteral transmission accounted for nearly all infections. HIV-1 DNA from the C2-V4 env region was sequenced, and phylogenetic analyses determined that 102 (79.7%) of the specimens were subtype E and 26 (20.3%) subtype B strains. All subtype B strains clustered with strains often referred to in previous studies as Thai B or B'. The interstrain nucleotide distance (C2-V4) within subtype E strains was low (mean, 6.8%), and pairwise comparisons with a prototype subtype E strain, CM244, showed limited divergence (mean, 5.6%). The subtype B stains showed greater interstrain divergence (mean, 9.2%) and were significantly divergent from the prototype B strain HIV-MN (mean, 13.0%; p < 0.0001). The subtype E strains had significantly lower mean V3 loop charge than did subtype B strains (p = 0.017) and, on the basis of analysis of amino acid sequences, were predicted to be predominantly (91%) non-syncytium-inducing (NSI), chemokine coreceptor CCR5-using (CCR5+) viruses. The subtype B strains had a higher mean V3 loop charge, and a smaller proportion (23%) were predicted to be NSI/CCR5+ viruses. This study demonstrates that most incident HIV1 infections among Bangkok IDUs are due to subtype E viruses, with a narrow spectrum of genetic diversity. The characterization of incident HIV-1 strains from 1995 to 1998 will provide important baseline information for comparison with any breakthrough infections that occur among IDUs in Bangkok who are participating in an HIV-1 vaccine efficacy trial initiated in 1999.

Amino Acid Sequence↗