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PubMed1997

The M5 (m5) receptor subtype: fact or fiction?

By comparison to the other subtypes of muscarinic receptors, very little is known about the binding properties, locations, mechanisms and physiological functions of the M5 (m5)* receptor subtype. Studies of the m5 receptor have been hampered by the lack of m5-selective ligands or antibodies and a source that endogenously expresses predominantly the m5 receptor subtype. We have developed a pharmacological labeling strategy using the non-selective muscarinic antagonist [3H]NMS, in the presence of muscarinic antagonists and toxins in green mamba venom to occlude the m1-m4 receptor subtypes, to selectively label the m5 receptor subtype. This m5-selective labeling approach, along with those developed for the other four receptor subtypes, has permitted for the first time a comparison of the relative expression levels and anatomical localizations of the five muscarinic receptor subtypes in the brain. The distribution profile of the m5 receptor is distinct from the other four subtypes and is enriched in the outer layers of the cortex, specific subfields of the hippocampus, caudate putamen, olfactory tubercle and nucleus accumbens. These studies have also demonstrated that the levels of m5 receptor protein expression are apparently higher and more widespread than anticipated from previous in situ hybridization and immunoprecipitation studies. Taken together, the results suggest a unique and potentially physiologically important role for the m5 receptor subtype in modulating the actions of acetylcholine in the brain.

Animals↗
PubMed1999

Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland.

A family of five subtypes of muscarinic acetylcholine receptors (mAChR) has been identified based on their molecular structures and second signal transduction pathways. In the present study, we examined the antagonist binding profiles of 9 muscarinic antagonists (atropine, 4-DAMP, pirenzepine, oxybutynin, tiquizium, timepidium, propiverine, darifenacin and zamifenacin) for human muscarinic acetylcholine receptor subtypes (m1, m2, m3, m4 and m5) produced by using a baculovirus infection system in Sf9 insect cells, and rat tissue membrane preparations (heart and submandibular gland). In a scopolamine methyl chloride [N-methyl-3H]- ([3H]NMS) binding assay, pirenzepine and timepidium displayed the highest affinities for the m1 and m2 subtypes, respectively, and both zamifenacin and darifenacin had the highest affinities for the m3 subtype, although the selectivities among the five subtypes were less than 10-fold. Propiverine showed a slightly higher affinity for the m5 subtype, whereas none of the drugs used in this study was uniquely selective for the m4 subtype. The binding affinities of muscarinic antagonists for rat heart and submandibular gland strong correlated with those for human cloned m2 and m3 subtypes, respectively. These data suggest that [3H]NMS binding studies using rat heart and submandibular gland might be useful methods which predict the affinities of test drugs for human muscarinic M2 and M3 receptor subtypes.

Animals↗
PubMed2003

Respiratory panic disorder subtype: acute and long-term response to nortriptyline, a noradrenergic tricyclic antidepressant.

The goal of the study was to describe with prospective methodology the therapeutic response to nortriptyline in the respiratory panic disorder (PD) subtype versus the non-respiratory subtype. A total of 118 PD outpatients (DSM-IV) were previously divided into respiratory (n=77) and non-respiratory (n=41) subtypes and then treated with nortriptyline for 1 year. Demographic and clinical features were compared in the two groups. Anxiety scales were administered before and during the treatment by raters who were blind to the subtype diagnosis. The principal instruments used to evaluate response were the Clinical Global Impression, the Sheehan Panic and Anticipatory Anxiety Scale, and the Panic Disorder Severity Scale. In the first 8 weeks of treatment (acute phase), the respiratory subtype had a significantly faster response on all the major scales. At the end of the study (week 52), there was no difference in the scale scores, and the reduction in panic attacks from baseline to end-point did not differ significantly between the two groups. In the respiratory subtype, the disorder had a later onset, was associated with a high familial history of mental disorder, and significantly more often required treatment with more than an occasional benzodiazepine. The non-respiratory subtype had significantly more previous depressive episodes. In conclusion, the respiratory PD subtype had a faster response to treatment with nortriptyline at 8 weeks than did the non-respiratory subtype, and an equivalent response after 1 year of treatment.

Acute Disease↗
PubMed2002

Influenza virus types and subtypes detection by single step single tube multiplex reverse transcription-polymerase chain reaction (RT-PCR) and agarose gel electrophoresis.

Influenza virus type and subtype specific primers were selected for use in reverse transcription polymerase chain reaction (RT-PCR). The selected primer sets were used in a single step RT-PCR of influenza virus RNA in multiplex format for the detection of virus type and subtypes. Three one step reaction conditions are optimized: (1) multiplex typing only, (2) multiplex subtyping of influenza A, and (3) multiplex typing and subtyping simultaneously. RNA from strains of influenza virus type A of subtypes H1N1, H3N2 and H5N1 and influenza virus type B was used for amplification and detection. The amplified DNA fragments were size analyzed for the presence of specific type and subtypes target DNA by agarose gel electrophoresis. The sensitivity of detection was about 0.01 TCID(50) for both influenza type A and B when amplification was for typing alone. In multiplex subtyping or multiplex typing and subtyping simultaneously, the sensitivities for types and subtypes specific bands were 0.01-0.1 TCID (50) in the tested volume.

Electrophoresis, Agar Gel↗
PubMedDate not supplied

Cluster subtypes within stage of change in a representative sample of smokers.

In this paper a three-level conceptualization of approaches to matching self-help behavior change strategies to individuals is presented based on the Transtheoretical Model of Change. Two of the model's intervention approaches, tailoring to Stage-of-Change and creating completely individualized interventions, have already been developed and implemented in previous research. A third intervention approach, in between stage-tailored and individualized, is targeting subtype groups within each Stage of Change. The subtype targeted intervention approach is in the initial development stage of empirically determining and validating the stage subtypes. Three studies are presented which investigate stage subtypes within a representative sample of 4,144 smokers in the Precontemplation, Contemplation, and Preparation Stages of Change. Within each Stage-of-Change study, two cluster analyses were performed using the Pros, Cons, and Situational Temptations from the Transtheoretical Model to establish cluster replicability. Cluster solutions were externally validated using the 10 Processes of Change and 2 smoking behavior variables. Four distinct subtypes were found in Precontemplation and Contemplation, and five subtypes were found in Preparation. These subtypes closely replicate subtypes previously found in a convenience sample of smokers and provide strong evidence for the existence of subtypes within the first three Stages of Change.

Adaptation, Psychological↗
PubMed1997

Gender differences in the frequency of schizophrenic subtypes in unselected hospitalized patients.

The phenotypic expression of the subtypes of schizophrenic disorders was studied in relationship to their relative frequency and the gender composition within each subtype using 374 successive DSM-III-R diagnosed schizophrenic patients. Two hundred and twenty-six of them were first admissions to a hospital. They were all diagnosed independently by three reviewers. While in the paranoid, the undifferentiated and the disorganized subtypes there was no significant difference between men and women, in the residual and the catatonic subtypes the frequency of men was more than three times greater than that of women. Among the 226 first admissions the frequency of the residual subtype was significantly lower than in the multiple admissions. The preponderance of male schizophrenic patients within the residual subtype indicates that they end up into this subtype, more frequently than women schizophrenic patients, whereas the greater preponderance of men in the catatonic subtype appears to reflect an intrinsic characteristic of this subtype.

Analysis of Variance↗
PubMed1996

Surface properties, morphology and protein composition of pulmonary surfactant subtypes.

Separation of surfactant subtypes is now commonly used as a parameter in assessing the amount of active compared with inactive material in various models of lung injury. The protein content, morphology and surface activity were determined of the heavy and light subtype isolated by differential centrifugation. Here we report the presence of surfactant proteins B and C in the heavy subtype but not in the light subtype. Adsorption studies revealed that separation of fast adsorbing bronchoalveolar lavage resulted in slowly adsorbing heavy and light subtypes. Surfactant, reconstituted from heavy and light fractions, did not show a high adsorption rate. It is concluded that the isolation procedures might result in a loss of fast adsorbing surfactant structures. Surface area cycling was used as a model in vitro for the extracellular surfactant metabolism. The heavy subtype is converted into the light subtype during conversion. Conversion performed with resuspended heavy subtype revealed the generation of a disparate subtype. Furthermore it was found that the conversion was dependent on preparation and handling of the samples before cycling. Finally, adsorption studies at low surfactant concentrations revealed a delayed adsorption of lipid-extracted surfactants compared with natural surfactants. These observations emphasize the importance of the (surfactant-associated protein A-dependent) structural organization of surfactant lipids in the adsorption process.

Adsorption↗
PubMed1987

Tissue-specific expression of the RI and RII sodium channel subtypes.

Anti-peptide antibodies that distinguish between the rat brain sodium channel subtypes referred to as RI and RII were prepared and used to determine their relative expression in nerve and muscle tissues. Sodium channels purified from rat brain are approximately 18% RI and 80% RII. In brain, the RII subtype is preferentially expressed with RI/RII ratios ranging from 0.07 in the hippocampus to 0.17 in the cerebral cortex. The RI subtype is preferentially expressed in more caudal areas of the central nervous system with values of RI/RII of 0.98 for medulla oblongata and 2.2 for spinal cord. Expression of additional unidentified sodium channel subtype(s) is detected in midbrain, medulla, and spinal cord, and expression of unidentified sodium channel subtypes predominates over expression of RI and RII in retina and optic nerve. The RI and RII subtypes are primarily expressed in the central nervous system and are not detected in significant numbers in skeletal or cardiac muscle, sympathetic ganglia, adrenal medulla, sciatic nerve, or cauda equina. The RII subtype appears first in development of both brain and spinal cord but declines in adult spinal cord as the RI subtype increases. The strict regional expression of these two sodium channel subtypes suggests that they may have distinct functional properties or physiological roles.

Animals↗
PubMed1992

Large and small vertebrate sensory neurons express different Na and K channel subtypes.

Sensory neurons of frog dorsal root ganglia (DRG) express at least two subtypes of voltage-gated Na channel and at least two subtypes of voltage-gated K channel. The Na channel subtypes have different sensitivities to tetrodotoxin (TTX) and different kinetics. The TTX-sensitive (TTX-s) Na channel inactivates rapidly and is blocked by nanomolar TTX. The TTX-insensitive (TTX-i) Na channel resists blockage by up to 100 microM TTX (it is blocked by saxitoxin) and inactivates 2-6 times more slowly. The two subtypes of voltage-gated K channel differ in activation kinetics: the fast subtype activates 2-8 times faster than the slow subtype. These Na and K channel subtypes are distributed differentially by cell size, falling into three major groups: (i) small cells with slowly activating K channels and a mixture of TTX-s and TTX-i Na channels; (ii) small cells with slowly activating K channels and TTX-s Na channels; and (iii) large cells with rapidly activating K channels and TTX-s Na channels. The contributions of these channel subtypes to the electrical properties of sensory neurons were investigated under conditions that minimized the contribution of Ca current. Under these conditions, action potential duration is correlated with the channel subtypes expressed: cells with both TTX-i and TTX-s Na channels and slowly activating K channels exhibit long-duration action potentials, cells with TTX-s Na channels and slowly activating K channels exhibit intermediate-duration action potentials, and cells with TTX-s Na channels and rapidly activating K channels exhibit short-duration action potentials.

Action Potentials↗
PubMed2003

Subtyping of Mycoplasma pneumoniae isolates based on extended genome sequencing and on expression profiles.

Mycoplasma pneumoniae isolates from patients, collected over a period of 12 years in Germany, were characterized by various methods (parameters) including multilocus sequence typing, restriction fragment length polymorphisms, Western blotting with mono-specific antibodies directed against selected proteins or with polyspecific antibodies directed against the Triton X-114-soluble protein fraction, and two-dimensional gel electrophoresis. The results for 91 isolates from Germany, which were complemented with 14 isolates from the USA and 10 isolates from France, clearly showed that M. pneumoniae is a highly uniform species and that most of the isolates could be assigned to one of the two subtypes 1 and 2. The members of one subtype differ from the other with respect to the sequence of the P1 gene, the ORF6 gene, the P65 gene, and by a typical DNA restriction fragment pattern. We observed four isolates (variants), which seemed identical by the above mentioned criteria, but did not belong to either one of the two subtypes. They showed most of the subtype 2-specific features, but differed in the sequence of the P1 gene and showed a variation in the restriction fragment pattern. The appearance of subtype 1 or 2 over the last 12 years in Germany showed a dominance of subtype 1 between 1989 and 1996 and a dominance of subtype 2 between 1997 and 1998. The variant (neither subtype 1 nor subtype 2) was only detected in 1991 and 1995 but it had no epidemiological consequences.

Adhesins, Bacterial↗
PubMed2000

Analysis of HIV-1 genetic subtypes in Finland reveals good correlation between molecular and epidemiological data.

The molecular epidemiology of HIV-1 genetic subtypes was studied in a cross-sectional sample collected from HIV-infected individuals living in Finland between 1988 and 1994 and compared with independently collected epidemiological data. Subtypes were determined by sequencing and phylogenetic analysis of the gag NCp7 and the env coding regions of PBMC provirus. Finnish viruses belonging to 7 subtypes were found. Two thirds (n = 70) of the sequences could be classified as subtype B, while others belonged to subtypes A, C, D, F and G and the circulating recombinant form AE(CM240) (n = 25). There were significant differences in gender distribution and mode-of-transmission between B-type infections and infections with the other subtypes. Most subtype B strains in Finland were associated with homosexual transmission and about half of these were acquired in Finland, while most individuals harbouring non-B infections indicated heterosexual transmission and direct or indirect contact with Africa or Southeast Asia. The heterogeneity of genetic subtypes in the country was in good agreement with the epidemiological data suggesting that a significant proportion of infections were imported. HIV-1 subtype determination may prove to be a valuable tool for providing objective epidemiological data.

Cross-Sectional Studies↗
PubMed2025

TCGA molecular subtypes in endometriosis-associated ovarian cancer: a systematic review and meta-analysis.

BACKGROUND: Endometriosis-associated ovarian cancer (EAOC) mainly includes endometrioid ovarian cancer (ENOC) and clear cell ovarian cancer (CCOC). The Cancer Genome Atlas (TCGA) revealed four molecular subtypes of endometrial cancer (EC) in 2013, which have been proven pivotal in the diagnostic, prognostic and therapeutic domains of EC. Existing evidence indicates that EC and EAOC molecular analysis have similar significance. This review aims to investigate the distribution, staging and prognostic characteristics of molecular subtypes in EAOC. METHODS: PubMed, Embase and Web of Science were systematically searched from January 2013 to December 2023 using predefined keywords. Patient characteristics, including stage and prognostic characteristics, were extracted from the selected studies. Data analysis was carried out using Stata 14MP. RESULTS: A total of 6 studies involving 1,133 patients with ENOC and 4 studies comprising 377 patients with CCOC were included. ENOC had a higher frequency of the POLE mutation (POLEmut) subtype (odds ratio (OR) = 2.29, 95% CI: 1.03-5.11, p = 0.043) and the mismatch repair deficient (MMRd) subtype (OR = 3.54, 95% CI: 2.05-6.11, p = 0.000) than CCOC; ENOC had a lower frequency of the no specific molecular profile (NSMP) subtype (OR = 0.55, 95% CI: 0.41-0.73, p = 0.000) and the p53 abnormal (p53abn) subtype (OR = 0.97, 95% CI: 0.67-1.42, p = 0.893). The hazard ratios (HR) of the p53abn subtype in ENOC were disease-free survival (DFS) (HR = 3.25, 95% CI: 1.46-7.21, p = 0.004) and progression-free survival (PFS) (HR = 4.11, 95% CI: 2.86-5.92, p = 0.000). The DFS of the p53abn subtype in CCOC was calculated (HR = 5.52, 95% CI: 3.43-8.90, p = 0.000). CONCLUSION: The TCGA subtypes of EC may exhibit similarities in prognosis between ENOC and CCOC.

Humans↗
PubMed1999

Human immunodeficiency virus type 1 subtypes differ in disease progression.

At least 10 different genetic human immunodeficiency virus type 1 (HIV-1) subtypes (A-J) are responsible for the AIDS pandemic. Much of the understanding of HIV-1 disease progression derives from studies in the developed world where HIV infection is almost exclusively subtype B. This has led many to question whether the properties and consequences of HIV-1 infection can be generalized across subtypes that afflict the majority of infected persons in the developing world. From 1985 to 1997, a prospective study of registered female sex workers in Senegal tracked the introduction and spread of HIV-1 subtypes A, C, D, and G. In clinical follow-up, the AIDS-free survival curves differed by HIV-1 subtype. Women infected with a non-A subtype were 8 times more likely to develop AIDS than were those infected with subtype A (hazard ratio=8.23; P=. 009), the predominant subtype in the study. These data suggest that HIV-1 subtypes may differ in rates of progression to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Different rates of disease progression of HIV type 1 infection in Tanzania based on infecting subtype.

BACKGROUND: Many different subtypes of human immunodeficiency virus (HIV) type 1 have been identified, particularly in sub-Saharan Africa. However, much remains unknown regarding the relative pathogenicity of these subtypes and their influence on the clinical progression of HIV infection. We examined prospectively the associations between HIV-1 subtypes A, C, and D and recombinant viruses, as well as the rates of disease progression in a cohort of seropositive women from Dar es Salaam, Tanzania. METHODS: A total of 428 pregnant mothers participating in a larger controlled trial of the effect of vitamin supplements were selected for DNA sequencing of their HIV-1 subtype. Plasma viral load was measured at baseline, and CD4+ cell counts was assessed at baseline and at regular intervals throughout the follow-up period. Proportional hazards regression (hazards ratio [HR]) analysis was used to measure the association between viral subtype and the rate of disease progression. RESULTS: Relative to patients with subtype A, patients with subtype D experienced the most rapid progression to death (HR, 2.27; 95% confidence interval [CI], 1.46-3.52) or to the World Health Organization stage 4 of illness (HR, 1.94; 95% CI, 1.20-3.14) and to a CD4+ cell count of <200 cells/mm3 (HR, 2.12; 95% CI, 1.42-3.17). After adjustment for viral load, CD4+ cell count, and other baseline covariates, the associations remained similar. CONCLUSIONS: We observed heterogeneity in the rates of disease progression of HIV-1 disease in infected persons, on the basis of the infecting subtype. Subtype D was associated with the most rapid progression of the disease, relative to the other 3 categories of viruses in our cohort.

Adult↗
PubMed1997

Presence of human immunodeficiency virus (HIV) type 1 subtype A infection in a New York community with high HIV prevalence: a sentinel site for monitoring HIV genetic diversity in North America. Centers for Disease Control and Prevention-Bronx Lebanon HIV Serosurvey Team.

To determine whether US residents are infected with subtypes of human immunodeficiency virus (HIV) type 1 other than subtype B (Western), the predominant North American subtype with a unique GPGR genetic sequence in the V3 loop, viruses from 22 HIV-infected adults were serotyped and subtyped. Twenty patients had subtype B (Western), of whom 15 had serotype B (Western), 3 had serotype A/C, 1 had serotype B (Thai), and 1 had a nontypeable serotype. Two had subtype A, both serotype A/C. Both subtype A-infected patients, only 1 of whom had been outside the United States, reported sex with persons traveling abroad, suggesting possible acquisition in the United States. Because US residents are infected with non-subtype B (Western) strains, US surveillance for HIV-1 diversity is needed to elucidate subtype-specific transmission patterns and pathogenesis and to guide evaluation and development of HIV diagnostic tests and vaccines.

Adolescent↗
PubMed2000

Introduction of HIV type 1 subtype E virus into South Korea.

Subtype E HIV-1 is the most prevalent strain in Southeast Asia. Although subtype B is prevalent in Korea, geographical distance and increases in travel may lead to the spread of subtype E in Korea. Therefore, we tried to identify and monitor the patterns of HIV subtype E virus introduction into Korea. The divergence of nucleotide sequences within the envelope region (V3 to V5) of Korean subtype E isolates ranged from 4.3 to 14.6% (n = 8; mean, 9.5 +/- 2.8%). In pairwise comparisons of subtype E isolates between Korea and other regions, the divergence of nucleotide sequences between 8 Korean and 16 Asian subtype E variants ranged from 1.3 to 15.2% (mean, 7.8 +/- 2.6%), whereas the divergence of nucleotide sequences between 8 Korean and 2 African variants ranged from 11.7 to 20.7% (mean, 15.4 +/- 2.2%). A phylogenetic tree showed that Korean subtype E isolates cluster with the Asian isolates but far from the African isolates. These epidemiological and molecular epidemiological data suggest that HIV-1 subtype E strains have been transmitted into Korea from endemic areas of Southeast Asia rather from Africa.

Adult↗
PubMed2001

HIV type 1 subtype E-infected patients with broadened, dual (B/E) V3 loop serology have increased cross-neutralizing antibodies.

The two prevalent subtypes of HIV-1 circulating in Thailand are subtypes E and B. While the most prevalent subtype continues to be E using molecular typing assays, immunologically, a subset of subtype E-infected patients (3.4% in 1997) have binding antibodies to both the E and B V3 loops in a peptide ELISA. To assess the potential function of this dual (B/E) V3 reactivity, plasmas from patients with genetically defined HIV-1 subtype E infection and either E or B/E V3 serotypes were compared for magnitude and breadth of neutralization of seven primary and laboratory-adapted subtype B and E viruses. Dually reactive (B/E) plasmas showed significantly increased cross-neutralizing activity against subtype B viruses (p < 0.001), and increased neutralization of the panel of viruses overall (p < 0.02), as compared to monoreactive E serotype plasmas. While the total envelope binding antibody titers to both subtype B and E envelopes did not differ significantly between the E and B/E plasmas, 67% of B/E plasmas neutralized >50% of the viruses in the panel, and only 14% of E plasmas showed this broadened neutralizing activity. These data suggest that dual (B/E) V3 loop reactivity may be a marker of broader immune recognition of HIV envelope epitopes in subtype E-infected patients. V3 loop antibody, perhaps in conjunction with antibodies to additional epitopes, may play a role in neutralization of virus isolates from Thailand.

Amino Acid Sequence↗
PubMed2003

Drug resistance profiles of recombinant reverse transcriptases from human immunodeficiency virus type 1 subtypes A/E, B, and C.

We have expressed purified recombinant reverse transcriptase (RT) from clinical isolates of human immunodeficiency virus subtypes B, C, and A/E in Escherichia coli. The drug sensitivities of these RTs were then determined for both nucleoside RT inhibitors (NRTIs) and nonnucleoside RT inhibitors (NNRTIs) in cell-free RT assays. Although A/E and C viruses contained numerous polymorphisms relative to subtype B (i.e., naturally occurring variations unrelated to drug resistance), the wild-type enzymes prepared from these or subtype A/E clinical isolates displayed <2-fold differences in drug sensitivities with regard to the active triphosphate active forms of NRTIs, as compared with RT expressed from BH-10 recombinant virus. Recombinant RTs from clinical isolates of subtypes B, C, and A/E that contained multiple resistance-associated mutations displayed expected variations in levels of resistance to the intracellular active forms of 3TC, ddI, ddC, and PMPA, that is, 3TCTP, ddATP, ddCTP, and PMPApp, respectively. Subtype A/E and C RT enzymes contained only minor NNRTI polymorphisms that distinguished them from wild-type subtype B enzymes and wild-type RTs from these various subtypes showed only 1- to 4-fold variability in IC(50) values for each of nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), and calanolide A. In contrast, RT enzymes from subtype B and C viruses harboring specific NNRTI mutations were highly resistant to all four tested NNRTIs. Subtype C variants containing the novel V106M resistance codon showed cross-resistance to all approved NNRTIs in cell-free RT assays.

Base Sequence↗