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PubMed1984

Classifying sexual disorders: the Diagnostic and Statistical Manual of the American Psychiatric Association.

The objectivity of the classification of sexual disorders in the third edition of the Diagnostic and Statistical Manual (DSM-III) of the American Psychiatric Association is explored via a critical examination of the replacement of homosexuality per se by ego-dystonic homosexuality, DSM's working concept of a mental disorder, the notion of a paraphilia, components of sexual identity, and the literature on variant sexual behaviors. It is argued that the same criteria that led to the removal of homosexuality per se as a mental disorder require the removal of all the paraphilias per se, there is no empirical warrant to justify their continued inclusion, and while there is legitimacy for a generalized ego-dystonic category, such ego-dystonias are only incidentally sexual. It is suggested that the present classification of sexual disorders is merely the codification of social mores.

Cues↗
PubMed1994

A new approach of acute lymphoblastic leukemia immunophenotypic classification: 1984-1994 the GEIL experience. Groupe d'Etude Immunologique des Leucémies.

Several classifications of acute lymphoblastic leukemias (ALL) have been proposed as increasing numbers of technologies and reagents allowed to better characterize leukemic tumor cells. The French Groupe d'Etude Immunologique des Leucémies (GEIL) proposes an immunologic classification of ALL derived from this group's initial attempts and on proposals published by others. Its first step is based on a scoring system where individual markers are assigned major, intermediate and minor weights on a scale of respectively 1.5, 1 and 0.5 points. Assignment to a given lineage requires a score of at least 2 in this lineage. Thus are identified the four levels "null", "pure", "variant" and "multiphenotypic", depending on score combinations in the three B, T and myeloid lineages. In a second step, within each of these classes, cell differentiation criteria are applied to further identify 4 subclasses within PreB-ALL (PreB1 to PreB4) and 4 within T-ALL (T1 to T4). ALL with only myeloid markers are referred to as M0. This classification was applied to a series of 1014 scorable ALL. Pure ALL represented respectively 72% in children under 16, and 64% in adults, PreB ALL being significantly more frequent in the former (p < 0.01). B-ALL and T-ALL were significantly (p < 0.05) more frequent in adults (respectively 11% and 27%) than in children (7% and 20%). Null and M0 ALLs appeared significantly (p < 0.01) more frequent in adults (3.4 and 3.2%) than in children (1 and 0.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2006

Serum C-reactive protein concentration and genotype in relation to ischemic stroke subtype.

BACKGROUND AND PURPOSE: C-reactive protein (CRP) has evolved as an inflammatory risk marker of cardiovascular disease. Several single-nucleotide polymorphisms at the CRP locus have been found to be associated with CRP levels. The aim of the present study was to investigate CRP levels and genetic variants in etiological subtypes of ischemic stroke. METHODS: The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) comprises 600 consecutive ischemic stroke cases (18 to 69 years) and 600 matched controls from western Sweden. Stroke subtypes were defined by the TOAST classification. Serum CRP levels were determined by a high-sensitivity immunometric assay. RESULTS: CRP levels were significantly higher for all ischemic stroke subtypes compared with controls, both in the acute phase and at the 3-month follow-up. After adjustment for traditional risk factors, CRP at follow-up was related to higher odds ratios (ORs) of overall ischemic stroke (OR, 1.25; 95% CI, 1.09 to 1.43) and large-vessel disease (OR, 1.48; 95% CI, 1.09 to 2.00). The CRP -286C>T>A, 1059G>C, and 1444C>T single-nucleotide polymorphisms showed significant associations with CRP levels. However, neither CRP genotypes nor haplotypes showed an association to overall ischemic stroke. CONCLUSIONS: This is the first large study on CRP in different TOAST subtypes in a young ischemic stroke population. CRP levels differed between etiological subtypes of ischemic stroke both in the acute phase and at the 3-month follow-up. CRP at follow-up was associated with overall ischemic stroke and the large-vessel disease subtype. Genetic variants at the CRP locus were associated with CRP levels, but no association was detected for overall ischemic stroke.

Adult↗
PubMed2006

Genetic risk profiles for Alzheimer's disease: integration of APOE genotype and variants that up-regulate inflammation.

BACKGROUND: A number of studies associate Alzheimer's disease with APOE polymorphism and alleles which favor the increased expression of immunological mediators such as cytokines or acute phase proteins. We integrated this information to better define risk and determine the relative importance of APOE and immunological mediators. METHODS: We investigated functional gene variants for APOE, IL-10 (3 loci), ACT (2 loci), HMGCR, IL-1alpha, IL-1beta, TNF-alpha, IFN-gamma, and IL-6 found for 260 AD patients and 190 controls enrolled in Northern Italy. A fuzzy latent classification approach, namely grade-of-membership analysis (GoM), was taken to identify extreme pure type risk sets, or profiles. This approach automatically relates individuals to each profile via graded membership scores. FINDINGS: Four extreme pure type risk sets were identified. Set I defined low intrinsic risk and had a low probability of carrying pro-inflammatory alleles or APOE epsilon4. Three sufficient risk sets were identified: early onset AD (set II) was characterized by a high density of pro-inflammatory alleles, a rapid cognitive decline and independent of APOE epsilon4. Late onset AD had a lower density (ages 65-74, set III), or a subset homozygous (ages 75+, set IV), for these alleles and a high probability of one or two APOE epsilon4 alleles. A total of 97% of the subjects who were cases strongly resembled, i.e. had at least 50% membership in, the sufficient risk sets, as did 25% of middle aged control subjects. IL-10, HMGCR, ACT, and IL-1beta gene variants were each more informative in identifying the risk sets than was APOE. INTERPRETATION: AD likely has many determinants including APOE polymorphism and gene variants that modulate innate immunity. Identification of these factors, risk prediction for individuals, and successful prevention and treatment trials require integration of relevant information.

Age Factors↗
PubMed2026

Gastric carcinoma classification in the WHO 6th edition (2026): Updated framework and emerging entities.

The sixth edition of the WHO Classification of Digestive System Tumours (2026) represents an important step in the continuing evolution of gastric carcinoma classification. While preserving morphology as the foundation of diagnosis, it incorporates advances in molecular pathology, genotype-phenotype correlations, tumour evolution, and predictive biomarker assessment. This review summarizes the development of the WHO classification from the third edition (2000) to the sixth edition (2026) and highlights its relationship with other major classification systems, including those of Laur&#xe9;n, Nakamura, and the Japanese Gastric Carcinoma Association (JGCA). Major histological categories remain largely unchanged; however, several important conceptual and diagnostic refinements have been introduced. These include recognition of crawling-type adenocarcinoma as a distinctive variant of tubular adenocarcinoma, subclassification of poorly cohesive carcinoma into signet-ring cell and non-signet-ring cell subtypes, introduction of the concept of pure signet-ring cell carcinoma, and increased emphasis on tumour evolution. The sixth edition also expands and refines the spectrum of uncommon gastric carcinoma subtypes, including gastric carcinoma with lymphoid stroma, AFP-producing carcinoma, micropapillary adenocarcinoma, gastric adenocarcinoma of fundic-gland type, and gastric sarcomatoid carcinoma. Crucially, molecular subgroups originally proposed by The Cancer Genome Atlas (TCGA) and actionable biomarkers-including HER2 (ERBB2), Claudin 18.2, mismatch repair deficiency/microsatellite instability (dMMR/MSI), and programmed death-ligand 1 (PD-L1)-have transitioned from research-based categories into essential tools for precision oncology. Rather than providing exhaustive diagnostic criteria, this review offers a conceptual framework and encourages consultation of the original WHO text for full details. These advances illustrate the transition of gastric carcinoma classification from a predominantly morphology-based system toward an integrated histomolecular framework that more closely links pathological diagnosis with tumour biology, prognostication, and therapeutic stratification.

Crawling-type adenocarcinoma↗
PubMed2006

Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients.

Warfarin is the most commonly used oral anticoagulant for treatment of thromboembolism, but adjustment of the dose appropriate to each patient is not so easy because of the large inter-individual variation in dose requirement. We analyzed single nucleotide polymorphism (SNP) genotypes of the VKORC1 and CYP2C9 genes using DNA from 828 Japanese patients treated with warfarin, and investigated association between SNP genotype and warfarin-maintenance dose. Five SNPs in VKORC1, 5' flanking-1413A > G, intron 1-136T > C, intron 2+124C > G, intron 2+837T > C and exon 3 343G > A, were in absolute linkage disequilibrium, and showed a significant association with daily warfarin dose of these patients. The median warfarin dose of patients with homozygosity for the minor allele was 4.0 mg/day, which is significantly higher than those heterozygous for the minor allele (3.5 mg/day) or those homozygous for the major allele (2.5 mg/day; P = 5.1 x 10(-11) in the case of intron 1-136T > C SNP). We then genotyped the CYP2C9 gene for the Japanese common genetic variant, CYP2C9*3 and, based on the genotype of these two genes, classified patients into three categories, which we call "warfarin-responsive index." The median warfarin daily dose varied significantly in this classification according to the warfarin-responsive index (2.0 mg/day for index 0 group, 2.5 mg/day for index 1 group, and 3.5 mg/day for index 2 group; P = 4.4 x 10(-13)). Thus, analysis of the combination of VKORC1 and CYP2C9 genotypes should identify warfarin-sensitive patients who require a lower dose of drug, allowing personalized warfarin treatment.

Anticoagulants↗
PubMed1990

A study of the predominant genotypes of bovid herpesvirus 1 found in the U.K.

The genotypic classification of 84 U.K. isolates of bovid herpesvirus 1 was determined by the restriction endonuclease technique. Preliminary studies with six enzymes (EcoRI, HindIII, HpaI, BamHI, PstI and BstEII) showed that the principal genotypic variants, including the live vaccine strains used in the U.K., could be identified from the digestion patterns with just two endonucleases: HindIII and HpaI. Isolates from the 1960s were all categorised as genotype 2b. From 1977 onwards, genotype 1 has predominated in mainland Britain, with occasional type 2b isolates. Type 2b viruses were isolated from both respiratory and genital disease cases. There was no evidence of genotypes 2a or 3 in the U.K.

Animals↗
PubMed2001

The molecular biology of von Willebrand disease.

von Willebrand disease (VWD) is a common autosomally inherited bleeding disorder associated with mucosal or trauma-related bleeding in affected individuals. VWD results from either a quantitative or qualitative deficiency of von Willebrand factor (VWF)--a glycoprotein with essential roles in primary haemostasis and as a carrier of coagulation factor VIII (FVIII) in the circulation. In recent years the identification of mutations in the VWF gene in patients with VWD has improved our understanding of the structure and function of the VWF protein, and has illustrated the importance of specific regions of VWF for its interaction with other components of the vasculature. The underlying genetic lesions and associated molecular pathology have been identified in many cases of type 2A, type 2B, type 2M, type 2N and type 3 VWD. However in the most common variant, type 1 VWD, the causative molecular defect is unknown in the large majority of cases. In the absence of an understanding of the molecular pathology underlying type 1 VWD, precise diagnosis and classification of this common disorder remains problematic.

Family Health↗
PubMedDate not supplied

The evolution of foot morphology in children between 6 and 17 years of age: a cross-sectional study based on footprints in a Mediterranean population.

Footprint evaluation is a widely used method for the determination of foot morphology, but its efficacy and validity are considered controversial. Dynamic footprints were obtained from both feet of 5,866 school-aged children (6-17 years old) to detect any foot changes during growth. The interpretation of the imprint was performed using a classification scheme consisting of 6 types of footprints. In this scheme, footprint types I and II represent the typical and intermediate high-arched foot, respectively. Types III and IV represent normal foot variants, while type V corresponds to the low-arched foot and type VI to the severe flat foot, the latter often encountered in pathological conditions. There was statistically significant difference (P<.05) in footprint-type frequencies between boys and girls of ages 7, 9, 11, 14, and 15, which probably indicates the difference in growth potential of the foot between sexes. The proportion of high- and low-arched foot types decreased with increasing age in both boys and girls. Even though critical changes of the foot are believed to occur during pre-school development, this study shows that considerable changes also take place during school age and until late adolescence.

Adolescent↗
PubMed1998

Mixed type basal cell carcinoma of the eyelids.

A retrospective histopathologic review of 97 patients with basal cell carcinoma of the eyelid was performed to determine the prevalence and behavior of tumors with a mixed pattern of growth. A mixed type basal cell carcinoma was defined as a tumor having a significant nodular or ulcerative component combined with an infiltrative component. Histologic classification of the 97 tumors yielded four (4.1%) that were multicentric, 67 (69.1%) that were nodular, one (1%) that was ulcerative, 13 (13.4%) that were infiltrative, and 12 (12.4%) that were the mixed variant. Follow-up was obtained on 8 of the 12 patients with mixed basal cell carcinoma. Three tumors recurred, but there were no tumor-related deaths. One of these patients underwent numerous eyelid resections over a 2-year period and then underwent an orbital exenteration. The authors conclude that mixed type basal cell carcinomas are not infrequent and behave as aggressively as basal cell carcinomas of the morphea type. A greater awareness and recognition of mixed type basal cell carcinomas by ophthalmologists and pathologists should result in fewer recurrences and better patient management.

Adult↗
PubMed2003

Genetic variability of hepatitis A virus.

Knowledge of the molecular biology of hepatitis A virus (HAV) has increased exponentially since its identification. HAV exploits all known mechanisms of genetic variation to ensure survival, including mutation and genetic recombination. HAV has been characterized by the emergence of different genotypes, three human antigenic variants and only one major serotype. This paper reviews the genetic variability and molecular epidemiology of HAV. Its evolutionary mechanisms are described with particular emphasis on genetic recombination and HAV mutation rate. Genotypic classification methods are also discussed.

Amino Acid Sequence↗
PubMed1978

Immunological heterogeneity of haemophilia B: a multicentre study of 98 kindreds.

An electroimmunoassay with a precipitating rabbit anti-human factor IX antiserum and an inhibitor neutralization assay with a non-precipitating homologous antibody were used to measure factor IX antigen (IX:Ag) in 117 patients from 98 kindreds with haemophilia B; and to investigate in a mixed population the incidence of different immunological types of the disease. Although the two assays showed an excellent correlation, the electroimmunoassay was selected for its simplicity as a criterion for classification. 52 kindreds, referred to as haemophilia B-, were characterized by severe deficiency of factor IX coagulant activity (less than 0.01--0.03 u/ml) and unmeasurable IX:Ag (less than 0.12 u/ml): this genetic variant of the disease appears to be related to a complete or marked suppression of factor IX synthesis. In 16 kindreds, a severe or moderately severe IX:C deficiency was associated with normal or increased levels of IX:Ag (haemophilia B+): among them, a subgroup of five kindreds could be identified by the additional abnormality of a prolonged Thrombotest clotting time (haemophilia BM). These patients are likely to be the expression of normal or increased synthesis of a factor IX molecule markedly defective in the site(s) responsible for coagulant activity. Reduced levels of IX:Ag (0.12--0.65 u/ml, characterized the remaining 30 kindreds, presenting with IX:C levels ranging from less than 0.01 to 0.21 mu/ml. In 28 there was a significant excess of IX:Ag over IX:C, suggesting a reduced capacity to synthesize the factor IX molecule accompanied by a variable defect in the coagulant site; the remaining two kindreds, which showed a concomitant reduction of IX:C and IX:Ag, are likely to be examples of a true reduction of factor IX synthesis.

Adolescent↗
PubMed1998

Clinicopathologic features and incidence of invasive lobular carcinoma in Japanese women.

Intending to clarify the true incidence of invasive lobular carcinoma of the breast in Japanese women as well as the frequency of unilateral multicentricity, 362 cases of clinically defined monocentric breast cancer without pre-operative biopsy (previously fine needle aspiration or needle biopsy were routinely carried out for every case) were examined by whole mammary gland serial sectioning. On the basis of pathology and the World Health Organization classification of breast tumors, each case was assigned to one of two main histologic types: invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). Invasive lobular carcinoma was further separated into classic and variant types by employing previously published criteria. Twenty-one cases of ILC (5.8%) were diagnosed, which is more than in most previous Japanese studies. Unilateral multicentric breast carcinoma was detected in 9.5% of ILC and 16.1% of IDC (the difference was found not significant). Microscopically, ILC tumors were found to be, on average, larger than IDC. Patients with classic type ILC tended to be younger than those with variant type or IDC. Estrogen receptor expression was found more frequently in variant type ILC than in classic type. These results suggest that the incidence of invasive lobular carcinoma of the breast in Japanese women is low and that unilateral multicentricity is not significantly higher in ILC than in IDC.

Adult↗
PubMed1986

Double connections in total anomalous pulmonary venous connection.

Three infants who underwent operation for total anomalous pulmonary venous connection had unobstructed drainage of all the pulmonary veins to both the coronary sinus and left vertical vein. In one patient the anatomy was demonstrated preoperatively and complete correction accomplished without difficulty, but in two patients the second connection was discovered only at postoperative reinvestigation. Arbitrary classification of total anomalous pulmonary venous connection into cardiac, supracardiac, infracardiac, and mixed types does not lend itself to description of such lesions and may obscure their clinical importance. For these less common variants of total anomalous pulmonary venous connection, a more detailed and precise definition of morphology facilitates accurate surgical repair.

Cardiac Catheterization↗
PubMed1972

Inactivation of the hemagglutinins of type A influenza viruses by physical and chemical means: an aid to classification.

The effects of temperature and treatment with sodium dodecyl sulfate, Tween 20, dithiothreitol, trypsin, or guanidine on the hemagglutinating capacity of six strains of type A influenza virus (A(0)/PR8/34, A(1)/CAME/46, A(2)/J305/57, A(2)/Bethesda/63, A(2)/HK/Aichi/68, and A(2)/HK/80/68), one strain of swine virus (A/Swine/76/?), and one equine strain (A/Equi-2/63) were determined. The two Hong Kong strains could be readily distinguished from the earlier A(2) strains by the resistance of their hemagglutinins to trypsin treatment and their inability to recover hemagglutinating capacity after removal of dithiothreitol from treated virus preparations. In these respects, the equine strain most closely resembled the Hong Kong variants. The pattern of hemagglutination inactivation also set the swine, PR8, and CAME strains apart from each other as well as from the other five strains. The results suggest that separation of type A viruses into groups by the pattern of inactivation of their hemagglutinins may be a valuable adjunct to standard serology for a more definite classification of these viruses.

Animals↗
PubMed2026

Prothrombin G20210A and Factor V Leiden Variants Are Not Associated With Thrombotic Events in Congenital Heart Disease: An Observational Trial.

BACKGROUND: Thrombotic events, including acute ischemic stroke, are more common in individuals with congenital heart disease (CHD). Whether common thrombophilia variants contribute to thrombotic risk in this population remains unclear. We evaluated whether prothrombin G20210A (F2 c.97G>A) and factor V Leiden (F5 c.1601G>A; p.Arg534Gln) are associated with thrombotic events in CHD. METHODS: Participants in the Pediatric Cardiac Genomics Consortium with exome sequencing and electronic medical record data were identified. Individuals were stratified by prothrombin G20210A and factor V Leiden genotypes, ventricular physiology, and antithrombotic therapy. The primary outcome was the presence of International Classification of Diseases (ICD) or Phecodes (phenotype codes) for thrombotic events. RESULTS: Among 4008 participants (median age, 11.4 [interquartile range, 5.1-17.9] years; 44.4% boys), thrombotic events occurred in 737 (18%), including 93 (13%) with acute ischemic stroke. Compared with the Genome Aggregation Database, the CHD cohort had a lower prevalence of heterozygous prothrombin G20210A and factor V Leiden variants. Variant prevalence did not differ between participants with and without thrombotic events. Single-ventricle CHD was associated with higher thrombosis frequency than biventricular CHD (35% versus 16%, P&#x2264;0.0001), without differences in variant prevalence. CONCLUSIONS: In this multicenter CHD cohort, prothrombin G20210A and factor V Leiden were not significantly associated with thrombotic outcomes, supporting recommendations against routine screening. Given low variant prevalence, the study was powered to exclude only large associations. Reduced variant frequency suggests survivorship bias beginning in fetal life. Larger integrated clinical-genomic studies are needed to refine thrombotic risk stratification in CHD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03347214.

Humans↗
PubMed2004

Molecular characterization of Epstein-Barr virus and oncoprotein expression in nasopharyngeal carcinoma in Korea.

BACKGROUND: We evaluated the characteristics of nasopharyngeal carcinoma in Korea, including its clinical, pathologic, and molecular features, especially emphasizing on the EBV strains involved, latent membrane protein 1 (LMP1) expression, and the alterations of matrix metalloproteinase 9 (MMP9) and E-cadherin expression. METHODS.: The presence of EBV was evaluated by EBER in situ hybridization, and the expression of LMP1, MMP9, and E-cadherin by immunohistochemistry. The characterization of EBV type and LMP1 variant was performed by PCR. RESULTS: EBER was detected in 55 of 57 cases (96%) of nonkeratinizing carcinoma (NKC) and undifferentiated carcinoma, but in only four of nine cases (44%) of squamous cell carcinoma (SCC). EBER positivity was much higher in the group with nodal metastases (p =.003). The predominant strain of EBV infection was type A (81%) and a 30-bp deletion LMP1 variant (77%). All EBER-positive SCCs were infected with EBV type A. LMP1 expression was detected in 36 of 59 (61%) patients with latent EBV infection and MMP9 in 41 of these 59 (69%). LMP1 positivity was much higher among the patients aged 50 years and younger. MMP9 expression was associated with LMP1 expression (p =.008), and nodal and distant metastasis (p =.019, p =.045). Loss of E-cadherin expression was correlated with MMP9 and nodal metastasis. The survival rate was much lower in patients with a higher TNM classification, stage, and a histology of SCC. EBER positivity was associated with a better prognosis in the Kaplan-Meier test, but had no prognostic value by Cox regression analysis. Loss of E-cadherin expression and nodal metastasis were also correlated with local recurrence and distant metastasis. CONCLUSION: EBV type and LMP1 variant had no significant influence on the clinicopathologic properties of tumor. However, there was a tendency toward a better survival in the EBV type B group. Histology and clinical staging were the two most important prognostic factors.

Adolescent↗
PubMed2000

Papillary squamous cell carcinoma of the uterine cervix: report of three cases and a review of its classification.

Papillary squamous cell carcinoma (SCC) of the uterine cervix has been defined as a malignant squamous cell lesion characterized by a papillary architecture with fibrovascular cores and moderate to severe dysplasia devoid of frank keratinization and koilocytic change. Papillary SCC should be histopathologically delineated from other rare variants of SCC with papillary features including verrucous and condylomatous carcinoma and the recently recognized (squamo-)transitional cell carcinoma of the uterine cervix. We report three cases of papillary SCC (FIGO stages IB, IV, and IVB) in postmenopausal women. Each tumor tested was positive for human papillomavirus (HPV) 16 and negative for HPV 6, 11 and 18 by general primer mediated polymerase chain reaction and subsequent enzyme-linked immunosorbent assay (PCR-ELISA). These findings 1) support the hypothesis that papillary SCCs (unlike verrucous carcinoma) are similar with regard to risk factors to (squamo-)transitional and condylomatous carcinoma; 2) suggest that HPV may play an etiologic role in at least some of these tumors; and 3) suggest that papillary SCC is the only subtype among squamous/(squamo-)transitional carcinomas that is associated with high-risk HPV infection in the absence of HPV-related histopathologic alterations.

Aged↗