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PubMed2001

Prostaglandin receptor subtypes, EP3C and EP4, mediate the prostaglandin E2-induced cAMP production and sensitization of sensory neurons.

Although a number of prostaglandin E(2) (PGE(2)) receptor subtypes have been cloned, limited studies have been performed to elucidate subtypes that subserve specific actions of this eicosanoid, in part because of a paucity of selective receptor antagonists. Using reverse transcription-polymerase chain reaction (PCR) and antisense oligonucleotides, we examined which prostaglandin E(2) receptor (EP receptor) subtypes are expressed in sensory neurons and which mediate the PGE(2)-induced increase in cAMP production and augmentation of peptide release. Reverse transcription-PCR of cDNA isolated from rat sensory neurons grown in culture revealed PCR products for the EP1, EP2, EP3C, and EP4 receptor subtypes but not the EP3A or EP3B. Preexposing neuronal cultures for 48 h to antisense oligonucleotides of EP3C and EP4 mRNA diminished expression of the respective receptors by approximately 80%, abolished the PGE(2)-stimulated production of cAMP, and blocked the ability of PGE(2) to augment release of immunoreactive substance P and calcitonin gene-related peptide. Pretreating with individual antisense against the EP2, EP3C, or EP4 receptors or combinations of missense oligonucleotides had no effect on PGE(2)-induced activity. Treatment with antisense to EP3C and EP4 receptor subtypes did not alter the ability of forskolin to increase cAMP or enhance peptide release. These results demonstrate that sensory neurons are capable of expressing multiple EP receptor subtypes but that only the EP3C and EP4 receptors mediate PGE(2)-induced sensitization of sensory neurons.

Animals↗

PubMed2026

Pre-Antiretroviral Therapy Vertical HIV-1 Transmission Risk in Uganda Varies by Sex of Child and Maternal Viral Subtype.

We analyzed perinatal transmission in a pre-antiretroviral therapy Ugandan cohort by maternal human immunodeficiency virus type 1 subtype and infant sex in 131 mother-child pairs. Among all children, if the mother was infected with subtype A there was a nearly 3-fold increased risk of perinatal transmission compared with subtype D (risk ratio [RR], 2.96 [95% confidence interval (CI), 1.46-6.01]; P = .008). When stratifying infants by both sex and maternal subtype, significantly more female (56.3% [9 of 16]) than male (9.1% [1 of 11]) infants born to mothers with subtype A were infected (RR, 6.19 [95% CI, .91-42.12]; P = .02). In contrast, among infants born to mothers with subtype D, transmission rates were comparable across sex (RR, 1.59 [95% CI, .57-4.41]; P = .39).

Humans↗

PubMed2006

Comparative analytical sensitivities of six rapid influenza A antigen detection test kits for detection of influenza A subtypes H1N1, H3N2 and H5N1.

BACKGROUND: Rapid and simple methods for diagnosing human influenza A (H5N1) disease urgently needed. The limited data so far suggest that the currently available rapid antigen detection kits have poor clinical sensitivity for diagnosis of human H5N1 disease. OBJECTIVES: To compare the analytical sensitivity of six commercially available rapid antigen detection kits for the detection of "human" (subtypes H1N1, H3N2) and "avian" (subtype H5N1) influenza A viruses. STUDY DESIGN: Six commercially available test kits for the detection of influenza A were investigated. Analytic sensitivity for the detection of two contemporary H1N1, two H3N2 and three H5N1 viruses was determined using virus culture as a reference method. RESULTS AND CONCLUSIONS: Each test kit detected the H5N1 virus subtypes as efficiently as they detected conventional human viruses of subtypes H1N1 or H3N2. However, limits of detection of influenza viruses of all subtypes by antigen detection kits were >1000-fold lower than virus isolation. Thus, the reportedly poor clinical sensitivity of these antigen detection kits for diagnosis of patients with H5N1 disease is not due to a difference of sensitivity for detecting avian influenza H5N1 compared to human influenza viruses.

Animals↗

PubMed1984

Subtypes of depression. Family study perspective.

To address the validity of subtype distinctions within a large family study of major depression, probands (N = 133) were classified into several non-mutually exclusive subcategories, including endogenous (n = 89), melancholic (n = 61), autonomous (n = 50), and delusional (n = 21). Age-corrected lifetime rates of depression and subtypes among first-degree relatives were then compared by the proband's depression subtype. Rates of major depression were highest for the relatives of probands with the autonomous and delusional subtypes, and while lower for the relatives of endogenous and melancholic probands, these rates were still higher than for the relatives of the remaining depressed probands or the relatives of normal controls. The depressed relatives of depressed probands with the endogenous, melancholic, autonomous, or delusional subtypes were more likely to have one of these subtypes than the depressed relatives of either the remaining depressed probands or the normal controls.

Adult↗

PubMed1998

The naturally occurring polymorphism Asp116-->His116, differentiating the ankylosing spondylitis-associated HLA-B2705 from the non-associated HLA-B2709 subtype, influences peptide-specific CD8 T cell recognition.

HLA-B27 molecules are interesting because of their strong association with ankylosing spondylitis (AS) and reactive arthritis (ReA). A pathogenetic role for these molecules has been postulated in presenting a putative "arthritogenic" peptide to CD8 T cells. The HLA-B*2709 subtype, although differing by a single amino acid (His116-->Asp116) from the widespread and strongly AS-associated subtype HLA-B*2705, is not found in patients. Since residue 116 interacts with the C terminus of the peptide, it is possible that the two subtypes differ in their antigen-presenting features. We show here that CD8 T cells can distinguish the two HLA-B27 subtypes when presenting a same epitope derived from Epstein-Barr virus-latent membrane protein 2. Moreover, alanine scanning mutagenesis analysis revealed that the peptide residues relevant for such recognition are different depending on whether HLA-B*2705 or -B*2709 molecules present the epitope. These results give support to the belief that functional differences determined by subtype-specific polymorphisms can have a pathogenetic relevance and open up a new scenario where subtle modifications within the peptide/HLA ligand might be responsible for the differential association between HLA-B27 subtypes and spondyloarthropathies.

Amino Acid Sequence↗

PubMed1981

Multiple histologic subtypes of non-Hodgkin's lymphoma: clinical and pathologic features.

Twenty patients with non-Hodgkin's lymphoma (NHL) had different histologic subtypes of NHL in multiple sites or in a single tumor mass either at the time of their initial biopsy and staging (13 patients) or in the course of their disease (seven patients). These 20 cases represent 3.7% of all patients with NHL seen at the University of Chicago between January 1968 and May 1979. The five-year actuarial survival rate for all 20 patients was 68%. For those 13 patients who had multiple histologic subtypes at the initial workup, the five-year survival rate was 45%; for the seven patients who developed a new histologic subtype later in the course of the disease, the five-year survival rate was 85%. In the latter group of patients, however, the initial biopsy specimens demonstrated better prognostic subtypes, and the median survival from the time of diagnosis of a new, less favorable histologic subtype averaged only four months. These findings indicate that the prognosis is related to the least favorable histologic subtype present, unless this is only a minor component of a composite lymphoma or is limited to one extranodal site.

Adult↗

PubMed2001

Differential subtyping of depression.

We studied a group of patients with depression divided into subtypes of non-chronic major depression, chronic major depression, and pure dysthymia. The purpose of this study was to determine if clinical and family history factors separated these types of depression. We reviewed records from semi-structured clinical interviews and abstracted data regarding factors that might differentiate these three depressive subtypes. In general we found what might be predicted from the definitions of dysthymia versus major depression, that is, ratings for severity of depression were lower for dysthymic patients as compared to patients with non-chronic or chronic major depression. We also found lower ratings for social functioning (GASF) for dysthymic patients as compared to the other depressive subtypes. Our study does not provide data to sufficiently separate these three subtypes. However, in the course of reviewing the literature on this topic, very few studies have separated patients into these distinct depressive subtypes. Further studies are needed to indicate if these subtypes can be meaningfully separated.

Acute Disease↗

PubMed2004

The histologic subtype of ovarian tumors affects the detection rate by pelvic washings.

BACKGROUND: Since its introduction more than 45 years ago, the pelvic wash has gained widespread acceptance and is used routinely use at most centers. However, widely varying figures have been reported regarding its sensitivity for peritoneal involvement in ovarian tumors. In the current study, the authors evaluated a consecutive group of pelvic (peritoneal or abdominopelvic) washings performed in the evaluation of adnexal masses to determine whether histologic subtype significantly affects the tumor detection rate using this procedure. METHODS: Reports from all washes performed over a 5-year period in the evaluation of adnexal masses were evaluated and correlated with those of the synchronously obtained histologic specimens. The sensitivity for each histologic subtype was calculated, with ovarian surface involvement and/or tumoral involvement of any peritoneal surface defined as the criterion standard. Cases with cytologic and histologic concordance were defined as true-positive or true-negative. Statistical significance was determined using the Fisher exact test. RESULTS: In the current study, 185 of 846 (21.9%) total washes were associated with malignant (n = 161) or borderline (n = 24) tumors involving the ovary. For the malignancies, the overall cytology detection rate was 25%. A comparison of the cytology detection rates for the individual histologic subtypes with the overall rate demonstrated that the serous carcinomas were more likely (P = 0.0144) and the clear cell carcinomas were less likely (P = 0.0452) to be detected in pelvic washings. Cytology detection rates for mucinous, endometrioid, and undifferentiated carcinomas did not appear to differ significantly (P > 0.05) from the average detection rate. The cytohistologic correlation rate (efficiency), sensitivity, and specificity for the 5 most common histologic subtypes (n = 130) were 79.23%, 50.77%, and 93.33%, respectively. Differences also were observed in the calculated sensitivity for each subtype: serous (n = 57), 71.4%; endometrioid (n = 30), 58.33%; clear cell (n = 19), 20%; mucinous (n = 13), 50%; and undifferentiated (n = 11), 50%. Borderline tumors demonstrated a sensitivity and specificity of 80% and 100%, respectively. CONCLUSIONS: In the current study, the pelvic wash was found to be a specific, but only moderately sensitive, technique for detecting peritoneal involvement in ovarian tumors. The histologic subtype of the underlying ovarian tumor was found to have an effect on the likelihood of detection of peritoneal involvement using this diagnostic assay.

Adenocarcinoma, Clear Cell↗

PubMed2001

Identification of a nonmammalian Golf subtype: functional role in olfactory signaling of airborne odorants in Xenopus laevis.

Attempts to identify the Galpha subtypes in the two compartments of the olfactory system from Xenopus, which are supposed to be specialized for detecting aquatic and volatile odorous compounds, revealed that a Galpha(o1) subtype is characteristic for the "water nose," the lateral diverticulum, whereas a novel Galpha(s) subtype predominates in the "air nose," the medial diverticulum. The newly identified Galpha(s)-type is more closely related to Galpha(olf) of rat and human than to the known Galpha(s)-isoform of Xenopus; it is therefore considered the first identified nonmammalian Galpha(olf) subtype. Sequence comparison of Galpha(olf) from amphibia and mammals revealed a particular conservation within the alpha-helical domains, which are supposed to control the GDP/GTP-exchange rate. The selective expression of different Galpha subtypes in the two anatomically separated and functionally specialized nasal compartments parallels the expression of distinct classes of olfactory receptors. Moreover, biochemical analysis revealed that stimulation with appropriate odorous compounds elicits the formation of inositol trisphosphate in the lateral diverticulum. In contrast, cyclic adenosine monophosphate signals were induced in the medial diverticulum, and this response appears to be mediated by the novel Galpha(olf) subtype. The data indicate that olfactory sensory neurons in each of the nasal cavities are equipped not only with defined sets of receptor types but also with a distinct molecular machinery for the chemo-electrical transduction process.

Amino Acid Sequence↗

PubMed2005

Gap-junction communication between subtypes of direction-selective ganglion cells in the developing retina.

The On-Off direction-selective ganglion cells (DSGCs) in the rabbit retina comprise four distinct subtypes that respond preferentially to image motion in four orthogonal directions; each subtype forms a regular territorial array, which is overlapped by the other three arrays. In this study, ganglion cells in the developing retina were injected with Neurobiotin, a gap-junction-permeable tracer, and the DSGCs were identified by their characteristic type 1 bistratified (BiS1) morphology. The complex patterns of tracer coupling shown by the BiS1 ganglion cells changed systematically during the course of postnatal development. BiS1 cells appear to be coupled together around the time of birth, but, over the next 10 days, BiS1 cells decouple from each other, leading to the mature pattern in which only one subtype is coupled. At about postnatal day 5, before the ganglion cells become visually responsive, each of the BiS1 cells commonly showed tracer coupling both to a regular array of neighboring BiS1 cells, presumably destined to be DSGCs of the same subtype, and to a regular array of overlapping BiS1 cells, presumably destined to be DSGCs of a different subtype. The gap-junction intercellular communication between subtypes of DSGCs with different preferred directions may play an important role in the differentiation of their synaptic connectivity, with respect to either the inputs that DSGCs receive from retinal interneurons or the outputs that DSGCs make to geniculate neurons.

Animals↗

PubMed2005

Subtypes of binge eating disorder based on psychiatric history.

OBJECTIVE: This investigation sought to identify subtypes of binge eating disorder (BED) based on history of mood disorder (MOOD) and substance use disorder (SUD). METHOD: Eighty-four women who met criteria for BED were administered semistructured interviews and completed self-report questionnaires assessing eating pathology, depressive symptoms, self-esteem, body dissatisfaction, and personality traits. RESULTS: Thirty-nine participants (46.4%) had a lifetime history of a SUD and 60 (71.4%) had a lifetime history of a MOOD. The SUD subtype was associated with a greater impulsivity and frequency of binge eating episodes compared with the no SUD subtype. The MOOD subtype participants reported greater distress, more psychopathology, less dietary restraint, lower self-esteem, more frequent binge eating, higher levels of negative affect, and more frequent trauma and abuse history than the no MOOD subtype. DISCUSSION: The results of this study indicate that subtypes of BED on the basis of MOOD and SUD may be associated with a more severe variant of the disorder.

Adult↗

PubMed2006

B2707 differs in peptide specificity from B2705 and B*2704 as much as from HLA-B27 subtypes not associated to spondyloarthritis.

HLA-B*2707 is associated with ankylosing spondylitis in most populations. Like the non-associated allotypes B*2706 and B*2709, it lacks Asp116 and shows preference for peptides with nonpolar C-terminal residues. The relationships between the peptide specificity of B*2707 and those of the disease-associated B*2705 and the non-associated subtypes were analyzed by determining the overlap between the corresponding peptide repertoires, the sequence of shared and differential ligands, and by comparing allospecific T cell epitopes with peptide sharing. The B*2707-bound repertoire was as different from that of B*2705 as from those of B*2706, B*2709, or the two latter subtypes from each other. Differences between B*2707 and B*2705 were based on their C-terminal residue specificity and a subtle modulation at other positions. Differential usage of secondary anchor residues explained the disparity between the B*2707-, B*2706-, and B*2709-bound repertoires. Similar differences in residue usage were found between B*2707 and both B*2704 and B*2706, as expected from the high peptide overlap between the two latter subtypes. T cell cross-reaction paralleled peptide sharing, suggesting that many shared ligands conserve their alloantigenic features on distinct subtypes. Our results indicate that association of HLA-B27 subtypes with ankylosing spondylitis does not correlate with higher peptide sharing among disease-associated subtypes or with obvious peptide motifs.

Amino Acid Motifs↗

PubMed1988

Factor B (BF) subtyping by isoelectric focusing: methods, nomenclatures, genetics and forensic application.

Usually factor B (BF) typing is performed by means of the traditional agarose gel electrophoresis. Using isoelectric focusing, the system can be extended by two common subtypes of BF F. The existence of BF F subtypes has in the meantime been confirmed by various authors and in different populations. Their inheritance has been proven by family- and mother/child analyses and molecular-genetic studies (correlation with restriction fragment length polymorphism). Different typing methods as well as different nomenclatures seem to indicate that the subtypes FA and FB (according to Geserick et al.) are identical with the Fb and Fa subtypes (according to Teng and Tan). At present, some confusion still exists for the less frequent variants and subtypes which possibly could be identified by direct comparison of the patterns. The BF system is a valuable marker in paternity testing. Its chance for exclusion of paternity in Caucasian populations has been calculated to be about 14% for agarose gel electrophoresis and increases to about 16% for BF F subtyping by isoelectric focusing. Preliminary results indicate that BF may also be used for typing of bloodstains (up to 2 weeks old).

Complement Factor B↗

PubMed2005

Clinical subtypes of delirium and their relevance for daily clinical practice: a systematic review.

BACKGROUND: Delirium is a disorder that besides four essential features consists of different combinations of symptoms. We reviewed the clinical classification of clusters of symptoms in two or three delirium subtypes. The possible implications of this subtype classification may be several. The investigation and exploration of clinical subtypes of delirium may provide information concerning the etiology, the pathogenesis, and the prognosis of delirium, but also may have therapeutic consequences. METHODS: We searched several database for English-language articles. Selected articles were cross-checked for other relevant publications. DATA SYNTHESIS AND CONCLUSION: We conducted a systematic review and retrieved ten clinical studies. The studies described in this review show different results, partly due to methodological problems and possibly by lack of a standard classification for delirium subtypes. According to the present literature a useful and reproducible method to classify (patterns of) symptoms in delirium subtypes seems to be the general rating of and division in to psychomotor subtypes. The Memorial Delirium Assessment Scale (MDAS) and the Dublin Delirium Assessment Scale (DAS) appear to be reliable methods, together with the new version of the Delirium Rating Scale (DRS-R-98).

Aged↗

PubMed2026

The machine-learning classifier ALLCatchR2 identifies 20 T-ALL subtypes across cohorts and age groups.

T-cell acute lymphoblastic leukemia (T-ALL) comprises molecularly diverse subtypes, but robust cross-cohort validations and operational gene-expression definitions are lacking. To establish a gene-expression-anchored framework for T-ALL subtyping, we aggregated 2314 transcriptomes (15 cohorts, age: 0.8-90.8 years). An extended unsupervised approach defined 17 main clusters and 3 subclusters in samples with high blast fractions. Supervised analyses added an overarching immature T-ALL (early T cell precursor [ETP]-like) definition and resolved the LMO2 γδ-like subtype. All clusters contained samples from at least two cohorts. Characteristic genomic driver enrichments were consistent across cohorts, while gene-expression clusters did not correspond exclusively to single driver events but also reflected developmental origins. A machine-learning classifier based on ALLCatchR, our B-cell acute lymphoblastic leukemia (B-ALL) classifier, identified these 20 transcriptomic subtypes and the immature T-ALL (ETP-like) signature with 0.995-1.0 accuracy in a validation set (n = 203). Testing the classifier on a second hold-out data set (n = 265 samples) showed that 92.7% of predictions matched with corresponding driver alterations. Across all samples, 83.2% of cases received high-confidence predictions, 7.3% candidate predictions, and 9.5% remained unclassified, largely because of low blast fractions. We identified a novel gene-expression cluster markedly enriched (P < 0.001) for clonal hematopoiesis mutations (IDH2 R140Q, DNMT3A) and a stem-/progenitor cell-like gene expression. This novel clonal hematopoiesis-related T-ALL subtype was observed in six cohorts and accounted for 8.9% of adults and 39.5% of patients aged >50 years. We extended ALLCatchR into ALLCatchR2, a free R package that now enables B-/T-lineage separation, gene-expression subtyping, blast estimation, and developmental annotation to harmonize T-ALL classification across studies and clinical contexts.

Journal Article↗

PubMed1993

Epstein-Barr virus subtype distribution in angioimmunoblastic lymphadenopathy.

The tissues of 16 patients bearing a T-cell lymphoma of angioimmunoblastic lymphadenopathy type (AILD-TCL) were investigated for the distribution of Epstein-Barr virus (EBV) subtypes 1 and 2. EBV-association had been proven in these cases by polymerase chain reaction (PCR) for EBV-DNA, in situ hybridization (ISH) for EBV-encoded small nuclear RNAs (EBER) and immunohistology for EBV-encoded latent membrane protein (LMP). PCR and EBER-ISH produced mostly identical results, but some cases were positive with only one of the 2 methods employed. LMP was detected in a few large cells of 8/13 cases. Twelve cases were investigated for the distribution of EBV subtypes. One case contained EBV genome of subtype 2, 3 cases contained subtype 1 and 4 cases contained both subtypes. Four cases could not be typed. These findings suggest that in AILD, as in AIDS-associated lymphomas and lymphomas of the lethal midline granuloma type, subtype 2 of EBV may occur, perhaps in relation to an immunodysfunction developing progressively in these patients.

Antigens, Viral↗

PubMed2005

Different somatostatin receptor subtypes are operating in the brain of the teleost fish, Coris julis.

Characterization of somatostatinergic (sst) neuronal activity through the application of nonpeptidyl agonists L-779,976 and L-817,818 which are highly specific for the sst receptors (sstr) sstr(2) and sstr(5), respectively, shows for the first time that sstr2, 5-like subtypes are the two major sstr subtypes operating in the brain of the teleost sea wrasse, Coris julis. A somewhat high but heterogeneous distribution pattern (> 30 < 180 fmol/mg wet tissue weight) of neurons expressing sstr2, 5 was reported in the different diencephalic regions plus in mesencephalon and telencephalon while low values were obtained in the cerebellum. Application of the above nonpeptidyl agonists permitted us to identify sstr2-like as the predominant subtype in telencephalic areas such as the entopeduncular nucleus (E) and postcommissural nucleus of the ventral telencephalon (Vp) as well as in hypothalamic and thalamic areas. At the same time high levels of neurons expressing sstr5-like, that greatly overlap those of sstr2-like in the diencephalic areas such as the anteroventral part of the preoptic nucleus (NPOav), the dorsal habenular nucleus (NHd) and the ventrolateral thalamic nucleus (VL), indicate that sstr2-like is very likely not the only sstr subtype acting in this fish brain. The predominance of sstr5-like in other brain areas is confirmed by the high quantities of this subtype in mesencephalic areas such as the torus longitudinalis (TLo). Overall, the discriminately differing densities of neurons expressing both subtypes seem to point to this system as a key molecular basis accounting for the distinct neurophysiological and behavioral sst-dependent activities in Coris julis.

Amides↗

PubMed2003

Epitopes corresponding to the envelope genetic subtype are present on the surface of free virions of HIV-1 group M primary isolates and can be detected in neutralization assays with extended incubation phases.

The hypothesis is that there are neutralizing epitopes on the surface of free virions of human immunodeficiency virus type 1 (HIV-1) that correspond to the genetic subtype of the envelope glycoprotein. Assays with extended incubation and reduced absorption phases are required to demonstrate neutralization with antibodies to these epitopes. These assays quantify virus infectivity, rather than reductions in release of antigen into culture supernatants. Neutralizing antibodies reduce virus infectivity by at least 80%, as scored by the presence/absence of antigen released after 14 days in culture of mitogen-transformed peripheral blood mononuclear cells (PBMCs). The epitopes are shared within different subtypes of group M, but not group O, isolates. Individual plasma, selected from three, independent panels of seropositive individuals, cross-neutralize within each subtype as well as the combinations of A with C, B with D or G, and C with CRF01_AE. Isolates within subtype B show the greatest variation in their resistance to neutralization, ranging from highly sensitive to highly resistant. No highly sensitive subtype D isolates were identified. Isolates from subtypes A, C, and CRF01_AE were all resistant. The strategic implication for vaccine design is that antibodies to a limited number of epitopes can neutralize more than 90% of the HIV-1 isolates that are circulating currently in the world. Also, since only antibodies that produce an all-or-nothing loss in virus infectivity can reasonably be expected to prevent the viremic phase after in vivo infection, assays with extended incubation, and culture phases should be used to monitor current efficacy trials.

Cross Reactions↗