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PubMed1996

Expression of alpha 2- and beta-adrenoceptor subtypes in human islets of Langerhans.

Sequences from cDNA molecules encoding alpha 2-adrenoceptor subtype genes were subcloned into prokaryotic vectors and riboprobes generated to hybridise selectively with each of the human alpha 2C2-, alpha 2C4- and alpha 2C10-adrenoceptor subtype mRNA species. The riboprobes were labelled with either 32P or digoxigenin and used to study the expression of alpha 2-adrenoceptor subtypes in sections of human pancreas, in isolated human islets of Langerhans and in clonal HIT-T15 pancreatic beta-cells. Using a ribonuclease protection assay protocol, expression of mRNA species encoding both alpha 2 C2 and alpha 2 C10 was demonstrated in preparations of isolated human islets of Langerhans. mRNA encoding alpha 2C4 was also detected in human islet RNA, using reverse transcription coupled with the polymerase chain reaction. In situ hybridisation was then employed to examine the distribution of each alpha 2-adrenoceptor subtype in sections of human pancreas. All three subtypes of alpha 2-adrenoceptor mRNA were identified in sections of formalin-fixed, paraffin-embedded human pancreas using riboprobes labelled with digoxigenin. Although some labelling of the three alpha 2-adrenoceptor mRNA subtypes was seen in the islets, the labelling was most intense in the exocrine tissue of the pancreas for each receptor subtype. The specificity of the digoxigenin-labelled RNA probes was confirmed in several control tissues and by in situ hybridisation studies using sense probes in the pancreas. The integrity of the pancreas sections was confirmed by in situ hybridisation with an antisense riboprobe derived from human insulin cDNA. The results demonstrate that multiple alpha 2-adrenoceptor subtypes are expressed in human pancreas. Both the exocrine and endocrine cells express more than one receptor subtype, although the islets stain less intensely than the bulk of the tissue suggesting that the islet cells may have lower levels of expression than the acinar tissue. The presence of alpha 2-adrenoceptor subtype mRNA species in pancreatic beta-cells was confirmed by Northern blotting of RNA extracted from the clonal beta-cell line, HIT-T15. Transcripts encoding each of the three cloned alpha 2-adrenoceptor subtypes were detected in HIT-T15 cells. Hybridisation of sections of human pancreas with oligodeoxynucleotide probes designed to hybridise with beta 2-adrenoceptor mRNA revealed expression of this species in islet beta-cells but not in the exocrine tissue of the pancreas.

Base Sequence↗
PubMed1999

Increase of HIV-1 subtype A in Central African Republic.

The concomitant presence of five distinct HIV-1 subtypes and of unclassified HIV-1 was reported in Bangui, Central African Republic (C.A.R.) between 1990 and 1991. This previous study was conducted in individuals belonging to the C.A.R. Armed Forces (FACA) Cohort and in patients from the University Hospital of Baugui. To follow the HIV-1 subtype distribution in Bangui over time, we conducted a cross-sectional surveillance of HIV-1 subtypes between 1987 and 1997 in three groups of individuals in Bangui: 47 men belonging to the FACA Cohort, 38 patients from the CNHUB hospital, and 51 individuals consulting the sexually transmitted diseases (STD) clinic. One hundred and ten HIV-1 were subtyped by heteroduplex mobility assay (HMA) and/or sequencing of env regions encompassing the V3 domain. By comparing the HIV-1 distribution in two time periods (1987-1991 and 1991-1996) in the FACA cohort, we observed a significant increase of subtype A from 43.7% to 83.9%. This subtype distribution does not seem specific to the FACA cohort, in that subtype A accounted for 46.7% of the HIV-1 infections in CNHUB patients in the first time period studied and for 69.6% in the second time period. In STD patients, subtype A infections were predominant in 1995 (72.7%) and 1997 (89.7%). Subtype E viruses could be identified in the second time period, but represented only between 6.5% and 21.8% of the infections in the three groups of individuals studied. Other subtypes (B, C, H) and non-classified HIV-1 in C2-V3 were detected with only a 3.2% to 9.1% frequency for each in the second time period. Phylogenetic analysis excluded infection by a single source for the individuals included in the study. Our data demonstrate an increase in the proportion of HIV-1 subtype A infections in Bangui that raises the question of a preferential transmissibility of specific HIV-1 variants.

Adult↗
PubMed1975

[Change of the prevalent subtype of hepatitis B antigen in acute hepatitis B infections (author's transl)].

Subtyping of hepatitis B antigen (HBs Ag) in patients with acute hepatitis B revealed subtype ay in 75 percent while subtype ad was much more common in chronic hepatitis B infections: 81 percent of HBs Ag positive blood donors and 76 percent of patients with HBs Ag positive chronic aggressive hepatitis revealed subtype ad. In contrast to blood donors and chronic hepatitis patients, a change of the prevalent subtype was noted in acute hepatitis patients between 1970 and 1974. Before May 1972, subtype ad was found in 67 percent of patients, whereas later subtype ay dominated in 93 percent. An unequal distribution of subtypes between acute and chronic forms of hepatitis B infections has been explained by differences in the virulence of virus strains. Our results suggest that the higher prevalence of subtype ad in longterm carriers may be due to infection during an earlier time when subtype ad was also common in acute infections. The change of the prevalent subtype in acute infections may be attributed to differences in contagiosity rather than differences in virulence of virus strains.

Acute Disease↗
PubMed1980

Influence of histologic subtype of small cell carcinoma of the lung on clinical presentation, response to therapy, and survival.

Patients with small cell carcinoma of the lung (SCCL) were histologically subtyped according to the Working Party for Therapy of Lung Cancer classification and were treated with combination chemotherapy. Of the 103 patients studied, 54 had the lymphocyte-like (oat cell) subtype, 41 had the intermediate cell subtype, and 8 had a mixture of the two. No significant difference in initial performance status, extent of disease, chemotherapeutic response rate, or survival (median, 10.2 mo) was noted among the histologic subtypes. When the histologic subtype of the primary biopsy tissue was compared with the subtype of other pathology specimens from the same patient, concordance of subtype was present in 74% of the patients. In the remaining 26%, two or three histologic subtypes were present. This study demonstrates no clinically significant differences among the various histologic subtypes of SCCL in patients extensively staged and treated with aggressive cytotoxic therapy. Because of this and because concurrent biopsy tissues from multiple sites in the same patient may vary in subtype, we conclude that prognostic or therapeutic decisions should not be based on SCCL subtype.

Carcinoma, Small Cell↗
PubMed1998

Quasispecies nature of hepatitis C virus (HCV) in patients with chronic hepatitis C with mixed HCV subtypes.

The quasispecies nature of hepatitis C virus (HCV) in patients with mixed HCV subtype infection was compared with that in patients with single HCV subtype infection. The number of HCV quasispecies was compared between 35 patients with mixed HCV subtype infection and 83 patients with single subtype infection. Subtype was determined by primers deduced from the core region and by line probe assay respectively. The number of quasispecies was evaluated by polymerase chain reaction amplification of hypervariable region 1 and by fluorescence single-strand conformation polymorphism analysis. There was no difference in clinical background between patients with mixed subtype infection and patients with single subtype infection. The number of quasispecies in patients with multiple subtype HCV infection was larger than in patients with single subtype HCV infection. The immunologic environments which allow the coexistence of more HCV quasispecies in patients with multiple HCV subtype infection differs from that in patients with single HCV subtype infection.

Adult↗
PubMed2006

Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study.

CONTEXT: Gene expression analysis has identified several breast cancer subtypes, including basal-like, human epidermal growth factor receptor-2 positive/estrogen receptor negative (HER2+/ER-), luminal A, and luminal B. OBJECTIVES: To determine population-based distributions and clinical associations for breast cancer subtypes. DESIGN, SETTING, AND PARTICIPANTS: Immunohistochemical surrogates for each subtype were applied to 496 incident cases of invasive breast cancer from the Carolina Breast Cancer Study (ascertained between May 1993 and December 1996), a population-based, case-control study that oversampled premenopausal and African American women. Subtype definitions were as follows: luminal A (ER+ and/or progesterone receptor positive [PR+], HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-, cytokeratin 5/6 positive, and/or HER1+), HER2+/ER- (ER-, PR-, and HER2+), and unclassified (negative for all 5 markers). MAIN OUTCOME MEASURES: We examined the prevalence of breast cancer subtypes within racial and menopausal subsets and determined their associations with tumor size, axillary nodal status, mitotic index, nuclear pleomorphism, combined grade, p53 mutation status, and breast cancer-specific survival. RESULTS: The basal-like breast cancer subtype was more prevalent among premenopausal African American women (39%) compared with postmenopausal African American women (14%) and non-African American women (16%) of any age (P<.001), whereas the luminal A subtype was less prevalent (36% vs 59% and 54%, respectively). The HER2+/ER- subtype did not vary with race or menopausal status (6%-9%). Compared with luminal A, basal-like tumors had more TP53 mutations (44% vs 15%, P<.001), higher mitotic index (odds ratio [OR], 11.0; 95% confidence interval [CI], 5.6-21.7), more marked nuclear pleomorphism (OR, 9.7; 95% CI, 5.3-18.0), and higher combined grade (OR, 8.3; 95% CI, 4.4-15.6). Breast cancer-specific survival differed by subtype (P<.001), with shortest survival among HER2+/ER- and basal-like subtypes. CONCLUSIONS: Basal-like breast tumors occurred at a higher prevalence among premenopausal African American patients compared with postmenopausal African American and non-African American patients in this population-based study. A higher prevalence of basal-like breast tumors and a lower prevalence of luminal A tumors could contribute to the poor prognosis of young African American women with breast cancer.

Adult↗
PubMed1981

Small-cell carcinoma of the lung--survival according to histologic subtype: a Veterans Administration Lung Group Study.

Six-hundred-twenty cases of small-cell carcinoma of the lung entered into the Veterans Administration Lung Group protocols 9-15 were retrospectively subdivided into histologic subtype, as proposed by the WHO (1977). Medium survival was greater for subtype No. 21 (lymphocyte-like) than for subtype No. 22 (intermediate) (17.2 vs. 12.6 weeks; P = .005). Patients with extensive disease survived longer with subtype No. 21 than subtype No. 22 (14.5 vs. 10.9 weeks; P = .026). However, no median survival difference was seen with limited disease. Survival for subtype 21 was greater than No. 22 (P = .016) for patients with poor initial performance status (IPS; Karnofsky 70 or less); for ambulatory patients (IPS 80-100) a survival advantage was seen for subtype No. 21 compared with No. 22, but did not quite reach statistical significance (P = .09). Survival in subtype No. 21 was better than in subtype No. 22 (24.3 vs. 14.7 weeks; P = .001) when no weight loss (less than 10 pounds over the six-month period prior to therapy) was documented. However, with weight loss (greater than 10 pounds) survival in each subtype was similar.

Body Weight↗
PubMed2003

Superficial radiotherapy for patients with basal cell carcinoma: recurrence rates, histologic subtypes, and expression of p53 and Bcl-2.

BACKGROUND: The histologic subtype of a basal cell carcinoma (BCC) may be an important factor for the success of a certain treatment modality. In the current article, the authors report recurrence rates among patients with BCC after superficial radiotherapy as well as Bcl-2 and p53 expression levels stratified by BCC subtype. METHODS: The authors performed a retrospective study of 175 BCCs in 148 patients (64 female patients and 84 male patients; mean age, 69 years) who were treated with radiotherapy. According to their histologic patterns, BCCs were classified as nodular (n = 103), superficial (n = 25), and sclerosing (n = 47). In addition, six patients with metatypic BCC were reviewed. Bcl-2 and p53 protein expression was examined on a tissue microarray of 60 BCC samples (18 nodular tumors, 12 superficial tumors, and 30 sclerosing tumors). RESULTS: The estimated 5-year recurrence rate for all patients with BCC was 15.8%: 8.2% for patients with the nodular subtype, 26.1% for patients with the superficial subtype, and 27.7% for patients with the sclerosing subtype (Kaplan-Meier analysis: P = 0.055). The median follow-up was 48 months. The mean time to recurrence was 20 months, and 86.4% of all recurrences occurred within 3 years after treatment. No gender-specific differences were observed. In addition, one of six metatypic BCCs recurred. Nuclear p53 immunoreactivity and low Bcl-2 expression were significantly correlated with the sclerosing subtype. Overall, 61.5% of patients developed additional neoplasms during follow-up (76 developed additional BCCs, 15 developed squamous cell carcinomas, and 6 developed Bowen disease). CONCLUSIONS: The sclerosing subtype of BCC was a risk factor for recurrence after radiotherapy. In contrast, excellent results were achieved for patients with predominant nodular subtype. Nevertheless, radiotherapy may be the therapy of choice for patients with all BCC subtypes, depending on the individual patient's characteristics. Expression analyses confirmed that p53 and Bcl-2 levels may be used as indicators for the aggressiveness of a BCC subtype. Due to the high incidence of additional skin malignancies, patients with BCC need careful follow-up.

Adult↗
PubMed1988

Distribution of muscarinic receptor subtypes within architectonic subregions of the primate cerebral cortex.

The regional distributions of muscarinic receptor subtypes (M1 and M2) in the macaque brain were investigated by in vitro receptor autoradiography. Putative muscarinic receptor subtypes were distinguished by their differential affinities for pirenzepine and carbachol in competition with [3H]-quinuclidinyl benzilate. Autoradiographic visualization of muscarinic receptor subtypes demonstrated marked regional and laminar variations that respected architectonic boundaries. The M1 receptor subtype was widely distributed throughout most cortical areas and was most intense over the superficial layers. Almost all limbic and paralimbic regions including the amygdala, hippocampus, orbitofrontal, temporopolar, parahippocampal, cingulate, and parolfactory areas displayed peak densities of the M1 receptor subtype. The M2 receptor subtype was selectively elevated in the primary sensory areas of all five sensory modalities, including the visual (area 17, V1), auditory (A1), and somatosensory (3b, S1) koniocortices, the anterior olfactory nucleus, and the gustatory area. The primary motor area also displayed a relative peak of M2 receptor subtype labeling. In the hippocampal formation, M1, M2, and nicotine receptors were distributed differentially, with each subdivision having a specific complement of cholinergic receptor subtype. The M1 receptor subtype was prevalent in the dentate gyrus, the CA4-CA3 region, and the CA1 ammonic sector. The M2 receptor subtype was concentrated in the CA2 sector, the subiculum, the rhinal cortices, and the parasubiculum. Putative neural nicotinic receptors, tagged with L-[3H]-nicotine, were most concentrated within the presubiculum.

Animals↗
PubMed2006

High specificity of V3 serotyping among human immunodeficiency virus type-1 subtype C infected patients with varying disease status and viral phenotype.

V3 serotyping is a technique for determining HIV-1 genetic subtype based on the binding of antibodies from patient sera or plasma to synthetic V3 peptides derived from subtype consensus sequences. Variation in the performance of this assay has been attributed to V3 sequence heterogeneity, the degree of which varies with patient disease progression, virus co-receptor usage, and genetic subtype. This study assessed the performance of a competitive peptide enzyme immunoassay (cPEIA) in samples from HIV-1 subtype C infected patients with varying disease profiles, including those with syncytium (SI) and non-syncytium-inducing (NSI) viruses. Out of 90 sera tested, 94.4% reacted strongly against the subtype C peptide. There was no significant difference in assay sensitivity among samples from advanced AIDS patients in which humoral immune response may be lower, nor among SI viruses which carry changes in the V3 sequence. Four samples were found to be cross-reactive with other subtypes and one acutely infected patient sample was non-reactive due to low anti-gp120 antibody titers. A significantly higher number of samples showed secondary reactivity to subtype A, compared to other subtypes (P < 0.005). In conclusion, the assay was able to identify HIV-1 subtype C infection with a high level of sensitivity (94%) irrespective of the stage of disease and therefore provides a valuable resource for the large-scale epidemiological monitoring of the spread of HIV-1 subtypes in South Africa.

Cell Line, Transformed↗
PubMed2001

HIV-1 LTR subtype and perinatal transmission.

Multiple subtypes of HIV-1 have been identified; however, there is little data on the relative transmissibility of viruses belonging to different subtypes. A matched case-control study addressed whether viruses with different long terminal repeat (LTR) subtypes were transmitted equally from mother to infant. The LTR subtype was determined for 45 matched cases and controls who participated in a clinical trial in Tanzania. HIV-1 subtypes A, C, and D and intersubtype recombinant sequences were identified. Exact matched logistic regression analysis showed that viruses containing subtype A or intersubtype recombinant LTRs were 3.2 and 4.8 times more likely to be transmitted from mother to infant than viruses with subtype D LTRs. Viruses containing subtype C LTRs were 6.1 times more likely to be transmitted than those with subtype D LTRs. These differences in transmission were independent of maternal CD4 at enrollment. Thus, it appears that HIV-1 subtype may be associated with differing rates of perinatal transmission in Tanzania.

Female↗
PubMed1995

HBsAg subtype distribution among different populations of HBsAg carriers in Spain.

Data concerning the HBsAg subtype distribution in Spain are out-of-date and confined to a restricted geographical area. Furthermore, the complex distribution observed in the countries surrounding Spain prevents any prediction. To obtain further data on HBsAg subtype distribution among Spanish HBsAg carriers, subtyping analysis (d and y determinants) was performed in 670 samples from subjects belonging to various epidemiological risk groups and coming from different geographical areas of the country. Similar frequencies were found for both mutually exclusive d/y subtype determinants among non-risk, normal HBsAg carriers from almost all geographical areas studied. In contrast, the ay subtype was clearly predominant (79-87%) among intravenous drug users, irrespective of their geographical origin. Thirteen different institutions for mentally retarded patients behaved as closed communities for HBV circulation, showing independent subtype distributions. Thus, no significant geographical variations were found for HBsAg subtype distribution in Spain. The prevalence of each particular subtype is mainly dependent on the epidemiological characteristics of the carriers studied. Subtype distribution was independent of the presence of HBeAg or HDV infection serum markers when homogeneous groups were considered separately. Atypical HBsAg phenotypes, either with coexistence or absence of both subtype determinants, were found in some cases.

Adult↗
PubMed2006

Distribution of Cryptosporidium subtypes in humans and domestic and wild ruminants in Portugal.

To investigate the transmission of cryptosporidiosis in Portugal, Cryptosporidium hominis and Cryptosporidium parvum from HIV-infected patients, cattle, and wild ruminants were characterized by sequence analysis of the 60-kDa glycoprotein (GP60) gene. Fourteen subtypes within nine subtype families were identified, and three of the subtype families (If, IIb, and IId) were restricted or largely limited to Portugal. Parasites from cattle from various regions in Portugal and wild ruminants in Lisbon showed limited genetic heterogeneity (only two subtype families). All wild ruminants had the same subtype, which was also the predominant subtype in cattle all over Portugal and was found in nine HIV-infected patients in Lisbon. Two other C. parvum subtypes were only restricted to limited locations. In contrast, human parasites displayed 13 subtypes in nine subtype families, with most of the infections caused by parasites in Ib, IIa, IIc, and IId families. Two of the C. parvum subtype families (IIc and IIb) had only been found in humans. The high overall parasite diversity and high percentage of C. hominis infections attributable to Ib and C. parvum infections to IId represent unique characteristics of Cryptosporidium transmission in humans in Portugal.

Animals↗
PubMed2006

Distribution of Cryptosporidium parvum subtypes in calves in eastern United States.

Cryptosporidium parvum DNA from 175 neonatal calves on 16 farms in eight eastern states in the United States was subtyped by sequence analysis of the 60-kDa glycoprotein gene to determinate the parasite genetic diversity. Six subtypes of the IIa subtype family were found. Subtype IIaA15G2R1, which is the predominant C. parvum subtype in calves in many parts of the world, was identified in 77% of the C. parvum DNA from calves. Several farms had more than one C. parvum subtype and a few calves had infections with mixed subtypes. Distribution of subtypes differed geographically. Diversity of C. parvum in calves in eastern United States was lower than that previously seen in Michigan and southern Ontario. The high prevalence of one subtype in calves worldwide and frequent detection of this subtype in humans suggests that parasite fitness probably plays an important role in transmission of cryptosporidiosis among cattle and in zoonotic infections.

Animals↗
PubMed2005

Amino acid variation within the fusion protein of respiratory syncytial virus subtype A and B strains during annual epidemics in South Africa.

Recent evidence of positive selection within the cytotoxic T-cell (CTL) epitopes of the highly conserved nucleoprotein of influenza virus raised the question of whether the CTL epitopes of Respiratory syncytial virus (RSV) are also affected by immune driven change over annual epidemics. The fusion protein (F-protein) of RSV is highly conserved within the two subtypes (A and B) and the most important target for the protective response. The position of various neutralizing epitopes has been mapped and characterized between RSV subtypes. CTL epitopes have also recently been mapped for the F-protein of subtype A, however variation within these epitopes between and within the subtypes has not been determined. To address this question, the F-proteins of 18 strains representative of all subgroup A and B genotypes identified in South Africa over a period of 5 years were sequenced. F-protein sequences were highly conserved within and between South African genotypes, with most variability occurring at the nucleotide level. Most of the amino acid differences identified within neutralizing and CTL epitopes were conserved within the subtypes, and therefore does not indicate immune selection. However, out of three CTL epitopes previously identified in subtype A, two (restricted to HLA B*57 and HLA A *01) were conserved only within subtype A, while the third (restricted to Cw*12) contained both subtype- and genotype-specific changes. These results suggest that most of the identified CTL epitopes are subtype A-specific and may not be recognized in subtype B viruses, while the HLA Cw*12 restricted epitope may also not be recognized efficiently in GA5 strains.

Amino Acid Sequence↗
PubMed1994

Solubilization of muscarinic receptor subtypes from baculovirus infected Sf9 insect cells.

Five different subtypes (human m1, m2, m5 and rat m3, m4) of muscarinic acetylcholine receptors (mAChR) were produced in insect Sf9 cells by infection with recombinant baculoviruses. N-[3H]methylscopolamine ([3H]NMS) has a similar affinity to each of these mAChR subtypes in cell membranes, while pirenzepine, 11-((2-[(diethylamino)methyl]-1-piperidinyl)acetyl)-5,11-dihydro-6H-pyri do- (2,3-b)(1,4)benzo-diazepin-6-on (AF-DX 116) and (+/-)-p-fluoro-hexahydrosiladifenidol (p-F-HHSiD) have a higher affinity for m1, m2 and m3, respectively, than for the other subtypes, indicating the maintenance of subtype specificity of mAChR in this system. Digitonin (1%, w/w) with sodium cholate (0.1%, w/w) solubilized 51% of m1, 36% of m2, 3% of m3, 28% of m4 and 17% of m5 mAChR from these cell membranes with retention of the [3H]NMS binding activity. Optimization of cholate concentrations resulted in solubilization of up to 50-60% for m1, m2 and m4, but up to 25% for m5 and 7% for m3. Optimal concentrations of cholate differed from one subtype to another. Sucrose monolaurate solubilized 21-43% of m1, m2 and m4, but only up to 12% for m5 and 2% for m3. 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonate (CHAPS) was practically ineffective in mAChR solubilization from Sf9 cell membranes for all subtypes investigated. Solubilization with digitonin and cholate had little influence on [3H]NMS affinity for m2 and m4, but decreased m1 and m5 affinity by 10-fold and that of m3 by more than 50-fold. These results indicate that the solubility and stability of mAChR in detergents differ among the subtypes, in spite of their structural similarities. These differences should be taken into account when comparing the five subtypes, particularly when determining the proportion of each subtype in a given tissue by precipitating the solubilized mAChR with subtype-specific antibodies.

Animals↗
PubMed1990

Discrimination of hepatitis B virus (HBV) subtypes using monoclonal antibodies to the PreS1 and PreS2 domains of the viral envelope.

We report the production and characterization of murine anti-PreS2 and anti-PreS1 monoclonal antibodies (mAb) and demonstrate their utility in discriminating hepatitis B virus (HBV) subtypes. On the basis of Western blotting and reciprocal competition binding to HBV virions, at least five distinct epitopes have been identified in the PreS domain: two within the PreS1 region and three within the PreS2 region. All PreS2 mAb bind M protein (gp33 and gp36) but only one group binds strongly to M and L proteins (p39 and gp42). This group determinant was mapped to peptide residues 120-145. The second group bound to an endoglycosidase F-sensitive epitope which is defined by a mannose-rich glycan at ASN 123 in the PreS2 region. The third group was mapped to peptide residues 150-174 and was reactive with the M envelope proteins but not L or S proteins on Western blots. All PreS1 mAb bind L protein but not M protein on Western blots. Using these mAb, HBV subtype assays were developed allowing evaluation of the Paris (1975) HBsAg subtype panel members along with other HBsAg-positive specimens. All Paris subtype members (except ayw2 and ayw3) could be easily distinguished by differential PreS2 mAb reactivity. The Paris subtypes, adw2, adw4, and adr, could be classified as distinct groups by PreS2 and PreS1 mAb binding. Specimens from Hong Kong and the United States classified as adw2 in the S region fell into two groups based on PreS2 mAb binding: one having reactivity similar to Paris adw2 subtype and the other having identical reactivity to Paris ayw1 subtype. Furthermore, some specimens classified as adr in the S region gave similar reactivity to the Paris ayr subtype in the PreS2 and PreS1 regions. One complicating factor in this approach toward subtyping was the discovery that some HBsAg positive sera may contain factors which block PreS epitopes. Grouping of HBV subtypes by PreS1, PreS2, and S mAb reactivity may allow better correlation with groupings based on HBV DNA sequence homology.

Animals↗
PubMed1991

Autoradiographic localization of subtypes of angiotensin II antagonist binding in the rat brain.

The non-peptide angiotensin II receptor compounds DuP 753 and WL 19 were utilized to detect subtypes of [125I]Sar1-Ile8-angiotensin II binding to angiotensin II receptors in the rat brain. In rat forebrain homogenates, DuP 753 and WL 19 produced a partial displacement of [125I]Sar1-Ile8-angiotensin II binding with DuP 753 displacing approximately 65% of the binding and WL 19 displacing approximately 35% of the binding. Using the techniques of quantitative receptor autoradiography, a distinct regional distribution of the subtypes of angiotensin II antagonist bind was detected. The angiotensin II-1 binding site (the receptor subtype preferentially displaced by DuP 753) appeared to predominate in the dipsogenic, cardiovascular and endocrine areas, including the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, anterior pituitary, dorsal motor nucleus of the vagus, nucleus of the solitary tract and the area postrema. Additional areas that contained predominantly the angiotensin II-1 receptor subtype were the ventral hippocampus, substantia gelatinosa of the trigeminal nucleus, nucleus of the lateral olfactory tract, piriform cortex and median preoptic nucleus. The angiotensin II-2 binding site (displaced by WL 19) was the predominant subtype in the thalamus, inferior olive, lateral septum, subthalamic nucleus, locus coeruleus, medial geniculate and medial amygdala. Several areas of the brain appeared to contain both receptor subtypes, including the superior and inferior colliculi, and the olfactory bulb. The angiotensin II-1 binding site was concentrated in areas of the brain involved in mediating angiotensin II effects on drinking, endocrine status and blood pressure. Localization of angiotensin II-2 sites in the thalamus and areas of the brain which process sensory information suggests a novel modulatory role for angiotensin II at this receptor subtype. These results indicate that DuP 753 and WL 19 are highly selective for angiotensin II binding site subtypes in the brain and that, in general these subtypes are compartmentalized in distinct brain regions. The non-peptide compounds used in these studies should provide excellent tools to discern the functional role of angiotensin II receptor subtypes in the brain.

Angiotensin II↗