Cestoda and monogenea of some teleost fishes off the Mudanya Coast (Sea of Marmara,Turkey)

Summary  The following helminths are reported from the Sea of Marmara off the Mudanya coast. Cestoda: Didymobothrium rudolphii in Solea solea, Clestobothrium crassiceps in Merluccius merluccius, tetraphyllidean larvae in Gobius niger, G. cobitis, M. merluccius, Eutrigla gurnardus, S. solea, Scorpaena scrofa and Progrillotia dasyatidis in G. niger. Monogenea: Trochopus pini in E. gurnardus, Ligophorus confusus in Liza ramada, Tetraonchoides paradoxus in Uranoscopus scaber, Microcotyle mugilis in L. ramada and Anthocotyle merluccii in M. merluccius.     

Helminth parasites of digestive tract of some teleost fish caught in the Dardanelles at Çanakkale, Turkey

Summary In this study the following parasites were found in fishes from the Dardanelles at ?anakkale: Cestoda: Bothriocephalus scorpii, Grillotia sp. and Scolex pleuronectis in Solea solea; Digenea: Ectenurus lepidus, Prodistomum polonii and Monascus filiformis in Trachurus trachurus, Hemiuridae metacercaria in S. solea, Lecithocladium excisum in Scomber scombrus, Lecithostaphylus retroflexus in Belone belone, Opechona bacillaris in Pomatomus saltatrix and S. scombrus and Schikhobalotrema sparisomae in Liza saliens; Nematoda: Hysterothylacium aduncum in T. trachurus, S. solea, Sparus aurata, P. saltatrix, L. saliens and Engraulis encrasicolus and Anisakis simplex in S. scombrus; Acanthocephala: Neoechinorynchus agilıs in L. saliens. No parasites were recovered from Sardinella aurita. Most of these species are well known in both the Mediterranean and Black Seas, but the Dardanelles appears to be the limit of the range of Anisakıs simplex.     

Reconsideration of normalization of Emax for heart size

Summary We previously proposedEmax Vd as a normalized form ofEmax for heart size relatively independent of wall volumeVm, whereEmax is the slope of the end-systolic pressure-volume line andVd is its volume axis intercept. WhenEmax Vd remains constant, average circumferential stress for a specified average circumferential strain in the ventricular wall also remains relatively constant, despite changes inVd/Vm around its normal value. Because accurate determination ofVd is difficult and stress for a givenEmax Vd changes slightly withVd/Vm, we investigated whetherVd could be replaced withVm in a normalizedEmax in this analysis. As the result, we obtained a function ofVd/Vm as the coefficient by which to multiplyEmax Vd orEmax Vm to yield stress for a specified strain. Using this coefficient, one can easily calculate stress for any strain fromEmax, Vd, andVm in order to compare myocardial contractility among left ventricles of different sizes. The present study confirms the importance ofVd as an indispensable reference volume for normalization ofEmax, as well as the low sensitivity ofEmax Vd as a normalizedEmax to changes inVd/Vm. Only whenVd/Vm remains constant isEmax Vm proportional toEmax Vd and can replaceEmax Vd.     

The expression of the mdm2 gene may be related to the aberration of the p53 gene in human hepatocellular carcinoma

The relationship between mdm2 gene expression and p53 gene mutation in hepatocellular carcinoma (HCC) and their correlation with the invasiveness of the disease were investigated in this study. Either the expression level of the mdm2 gene or the mutation rate of the p53 gene was higher in HCC than in paratumor liver tissues. Studies on the relationship between mdm2 and p53 revealed that mdm2 gene expression in HCC without p53 mutation was higher than when there was p53 mutation, while the p53 mutation rate in HCC with mdm2 overexpression was significantly lower than in HCC without mdm2 overexpression. Among 23 HCC with invasion, mdm2 gene overexpression was found in 6 patients while p53 mutation was found in the other 11 patients, and only 1 patient was found to have both mdm2 overexpression and p53 mutation. These results indicated that either mdm2 overexpression or p53 mutation may be related to the invasiveness of HCC. Considering that an autoregulatory feedback loop between the mdm2 and p53 genes may exist, wild-type P53 can induce the expression of mdm2 via a p53-binding site in the mdm2 gene, while MDM2 protein functions as a negative regulator of P53 protein. These results also suggest that mdm2 may be related to the high invasiveness of HCC through inactivating the tumor-suppressor function of the p53 gene. Received: 8 September 1997 / Accepted: 17 December 1997     

Digenetic trematodes of some teleost fish off the Mudanya Coast (Sea of Marmara, Turkey)

Summary A total of 200 fishes belonging to nine species were sampled from the Sea of Marmara. Thirteen trematode species were recorded in the intestine of these hosts: Helicometra fasciata and Diphterostomum brusinae in Zosterisessor ophiocephalus; Monascus filiformis in Trachurus trachurus; Dicrogaster purpusilla, Schikhobalotrema sparisomae and Sacccocoelium obesum in Liza saliens; Macvicaria alacris, H. fasciata and Gaevskajatrema perezi in Symphodus tinca; Anisocladium fallax and A. capitellum in Uranoscopus scaber; Stephanostomum caducum in Merluccius merluccius; Bucephalus marinus, Stephanostomum gaidropsari and H. fasciata in Gaidopsarus mediterraneus; H. fasciata in Scorpaena scrofa and Gobius cobitis.     

Platelet-derived growth factor receptor family mutations in gastrointestinal stromal tumours

Objective. Activating mutations of either KIT or platelet-derived growth factor receptor alpha (PDGFRA) genes are present in the majority of gastrointestinal stromal tumours (GISTs). The type of gene mutation is associated with the aggressiveness of the disease, response to imatinib therapy, and the tumour site in the gastrointestinal tract. However, a subgroup of GISTs does not harbour these mutations. Material and methods. Thirty-three GISTs were studied for mutations in exons encoding the juxtamembrane and the activation loop domains of KIT, PDGFRA, PDGFRB, CSF1R, and FLT3 genes using denaturing high-performance liquid chromatography and gene sequencing. Results. Twenty-two (67%) GISTs had mutation in KIT and 3 (9%) in PDGFRA. The three PDGFRA mutations were all detected in exon 18 of the gene. Three of the 5 GISTs that had weak to moderate KIT expression had a PDGFRA mutation as compared to none of the 26 cases with strong KIT immunopositivity (p=0.022). No mutations were found in PDGFRB, CSF1R or FLT3 in the 8 cases that did not harbour KIT or PDGFRA mutations. Conclusions.KIT and PDGFRA are the most commonly mutated type III receptor tyrosine kinase genes in GIST. GISTs with PDGFRA mutations often have reduced expression of the KIT protein in immunohistochemistry, suggesting that immunohistochemistry may be potentially useful in identification of such GISTs.     

Step response analyses of the cardiovascular system and their application to the measurement of systemic and pulmonary vein compliances

Summary A theoretical analysis of the step response in the closed cardiovascular system induced by a sudden shift of the right cardiac output curve predicted that if the relations of the right heart output (COr) and the total systemic capillary flow (CFs) to the systemic venous pressure (Psv) are linear, then the time course ofPsv change will become monexponential with a time constant T given by T=Csv/(Gr + Gs), whereCsv is the systemic vein compliance andGr andGs are the conductances of the transientCOr - Psv andCFs - Psv relationships. A similar prediction was obtained for the time constant T of the pulmonary vein pressure (Ppv) response to the step change in the left cardiac output (COl) curve, pulmonary vein compliance (Cpv) and the conductances of theCol curve, and the pulmonary capillary flow (CFp) curve againstPpv. The actualPsv orPpv changes following sudden alteration of theCOr orCOl curve by inflation and deflation of the balloon in the right or left atrium revealed monoexponential time courses. Semilogarithmic plots of the transient vein pressure changes yielded correlation coefficients of –0.995 ± 0.006 (means ± SD) in 11 curves forPsv and 0.977 ± 0.017 in 16 curves forPpv (P<0.01). The assumed linearity of dynamicCOr andCOl curves was confirmed by beat by beatCOr - Psv andCOl - Ppv relationships during the step responses, except for the first few beats immediately after the balloon maneuver. The linearity of the dynamicCFs curve was examined by measuringCFs with a double-step balloon maneuver so as to cause rapid equilibrium betweenCOr andCFs at varied moments of the transient process. The correlation coefficient betweenCFs andPsv thus obtained was 0.98 ± 0.04 (P<0.01). A similar linearity of the dynamicCFp -Ppv relationship was suggested from their steady-state curves. The values ofCsv calculated from the experimental data were 1.70 ± 0.12 ml/mmHg/kg body wt in 11 curves and those ofCpv were 0.13 ± 0.03 ml/mmHg/kg in 15 curves. These results are mostly consistent with those previously reported.     

TET2, ASXL1, IDH1, IDH2, and c-CBL genes in JAK2- and MPL-negative myeloproliferative neoplasms

Mutations in the TET2 and ASXL1 genes have been described in approximately 14% and 8% of patients, respectively, with classic myeloproliferative neoplasms (MPN), but their role as possible new diagnostic molecular markers is still inconclusive. In addition, other genes such as IDH1, IDH2, and c-CBL have also been reported in several myeloid neoplasms. We have studied the mutational status of TET2 (complete coding region), ASXL1 (exon12), IDH1 (R132), IDH2 (R140 and R172), and c-CBL (exons 8 and 9) in 62 MPN patients (52 essential thrombocythemia (ET), five polycythemia vera (PV), and five primary myelofibrosis (PMF)) negative for both JAK2 (V617F and exon 12) and MPL (exon 10) mutations. Pathogenic alterations in the TET2 gene were detected in three out 52 ET cases (4.8%). ASXL1 gene pathogenic mutations were also detected in three cases (two ET and one PMF). One ET patient harbored, simultaneously, one TET2 and one ASXL1 mutations. Mutations in the TET2 and ASXL1 genes showed no association with the JAK2 46/1 haplotype. Analysis of a JAK2V617F-positive cohort of 50 ET patients showed no mutations in either the TET2 or ASXL1 genes. Regarding IDH1, IDH2, and c-CBL genes, no mutations were found in any patient. In conclusion, TET2 and ASXL1 pathogenic mutations are found in 8% of MPN lacking JAK2 and MPL mutations, whereas IDH1, IDH2, and c-CBL mutations are not detected in this subset of patients.     

Overexpression of hepatic 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients

11-β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to cortisol, mainly in the liver and visceral adipose tissue (VAT), and has been implicated in several metabolic disorders. The absence of systemic hypercortisolism in central obesity could be due to increased inactivation of cortisol to its tetrahydrometabolites by the hepatic enzymes 5α- and 5β-reductases. Our aim was to assess the expression of the reductases in the liver and of 11β-HSD1 in the liver and VAT in morbidly obese patients and to analyze their association with clinical, anthropometric, and biochemical parameters. Hepatic and VAT samples were obtained during bariatric surgery. 5α- and 5β-reductases, 11β-HSD1, and 18S expression was measured using real-time polymerase chain reaction. Anthropometric and biochemical variables were analyzed. Forty-one patients were recruited (age, 41.8 ± 10.6 years; body mass index, 42.1 ± 6.6 kg/m²; 71% women). The expression of hepatic 5α- and 5β-reductases was positively correlated (r = +0.53, P = .004), and their expression levels were correlated with hepatic 11β-HSD1 expression (r = +0.61, P < .001 for 5α-reductase and r = +0.50, P < .001 for 5β-reductase). Hepatic 5α-reductase was associated with insulin (r = +0.34, P = .015). Visceral adipose tissue 11β-HSD1 expression was associated with glucose (r = +0.37, P = .025) and insulin (r = +0.54, P = .002). Our results showed that 5α-reductase and VAT 11β-HSD1 expressions were associated with insulinemia. These findings suggest that overexpression of 5α-reductase, through a higher inactivation of cortisol in the liver, could have a protective role in preserving hepatic sensitivity to insulin. The overexpression of liver reductases in obesity could be an adaptive response to an increase in cortisol production by the liver and visceral 11β-HSD1 to avoid systemic hypercortisolism.     

Structural characteristics of the cag pathogenicity island and its significance in the classification of Chinese strains of Helicobacter pylori

OBJECTIVE: To investigate the structural characteristics of the cag pathogenicity island (PAI) and its significance in the classification in Chinese strains of Helicobacter pylori. METHODS: In 107 H. pylori strains isolated from Chinese patients, cagA, cagI, cagII, the cagI?cagII junction and IS605 were studied by using the polymerase chain reaction. RESULTS: The positive rates in Chinese H. pylori strains were 95.3% for cag PAI, 92.5% for cagA, 86.9% for cagI and 66.4% for cagII. There was no statistical difference among H. pylori strains from chronic gastritis, peptic ulcers or gastric carcinoma in the detectable rate of cag PAI, cagA, cagI or cagII (P > 0.05). Of the cag PAI‐negative strains, four came from cases of chronic gastritis and one from a patient with cardiac cancer. The products of the cagI?cagII junction were found in only five strains. The continuous cag PAI was much more common in duodenal ulcers than in chronic gastritis (P < 0.01). The positive rates of cagI and cagII were markedly different in chronic gastritis (P < 0.05). One strain of H. pylori tested positive for cagA but negative for other regions of the cag PAI. IS605 was less common in duodenal ulcers than in chronic gastritis (P < 0.05). The amplified fragment of IS605 in one strain from a gastric carcinoma was approximately 1580 bp in size, which was much longer than that in other strains. CONCLUSION: Our results indicate that the cag PAI is very common in Chinese strains of H. pylori. The structural variety of the cag PAI might be related to the virulence of H. pylori. It is suggested that H. pylori may be classified into different virulence groups according to differences in the structure of the cag PAI.     

Daily differential expression of melatonin‐related genes and clock genes in rat cumulus–oocyte complex: changes after pinealectomy

This study investigated the maturational stage (immature and mature ovaries) differences of mRNA expression of melatonin‐forming enzymes (Aanat and Asmt), melatonin membrane receptors (Mt1 and Mt2) and putative nuclear (Rorα) receptors, and clock genes (Clock, Bmal1, Per1, Per2, Cry1, Cry2) in cumulus–oocyte complexes (COC) from weaning Wistar rats. We also examined the effects of pinealectomy and of melatonin pharmacological replacement on the daily expression of these genes in COC. qRT‐PCR analysis revealed that in oocytes, the mRNA expression of Asmt, Mt2, Clock, Bmal1, Per2, and Cry1 were higher (P < 0.05) in immature ovaries than in the mature ones. In cumulus cells, the same pattern of mRNA expression for Asmt, Aanat, Rorα, Clock, Per1, Cry1, and Cry2 genes was observed. In oocytes, pinealectomy altered the daily mRNA expression profiles of Asmt, Mt1, Mt2, Clock, Per1, Cry1, and Cry2 genes. In cumulus cells, removal of the pineal altered the mRNA expression profiles of Mt1, Mt2, Rorα, Aanat, Asmt, Clock, Bmal1, Per2, Cry1, and Cry2 genes. Melatonin treatment partially or completely re‐established the daily mRNA expression profiles of most genes studied. The mRNA expression of melatonin‐related genes and clock genes in rat COC varies with the maturational stage of the meiotic cellular cycle in addition to the hour of the day. This suggests that melatonin might act differentially in accordance with the maturational stage of cumulus/oocyte complex. In addition, it seems that circulating pineal melatonin is very important in the design of the daily profile of mRNA expression of COC clock genes and genes related to melatonin synthesis and action.     

Association between variants in the genes for adiponectin and its receptors with insulin resistance syndrome (IRS)-related phenotypes in Mexican Americans

Aims/hypothesis The aim of this study was to examine whether genetic variation in ADIPOQ, ADIPOR1 and ADIPOR2 may contribute to increased susceptibility to components of the insulin resistance syndrome (IRS). Materials and methods We genotyped single-nucleotide polymorphisms (SNPs) in ADIPOQ, ADIPOR1 and ADIPOR2 in Mexican American subjects (N=439) and performed an association analysis of IRS-related traits. Results Of the eight SNPs examined in the ADIPOQ gene, rs4632532 and rs182052 exhibited significant associations with BMI (p=0.029 and p=0.032), fasting specific insulin (p=0.023 and p=0.026), sum of skin folds (SS) (p=0.0089 and p=0.0084) and homeostasis model assessment of insulin sensitivity (HOMA-%S) (p=0.015 and p=0.016). Two other SNPs, rs266729 and rs2241767, were significantly associated with SS (p=0.036 and p=0.013). SNP rs7539542 of ADIPOR1 was significantly associated with BMI, SS and waist circumference (p=0.025, p=0.047 and p=0.0062). Fourteen of the ADIPOR2 SNPs were found to be significantly (p<0.05) associated with fasting plasma triglyceride concentrations. Four of these SNPs (rs10848569, rs929434, rs3809266 and rs12342) were in high pairwise linkage disequilibrium (r ²=0.99) and were strongly associated with fasting triglyceride levels (p=0.00029, p=0.00016, p=0.00027 and p=0.00021). Adjusting for the effects of BMI and HOMA-%S on triglyceride concentrations increased significance to p=0.000060 for SNP rs929434. Bayesian quantitative trait nucleotide analysis was used to examine all possible models of gene action. Again, SNP rs929434 provided the strongest statistical evidence of an effect on triglyceride concentrations. Conclusions/interpretation These results provide evidence for association of SNPs in ADIPOQ and its receptors with multiple IRS-related phenotypes. Specifically, several genetic variants in ADIPOR2 were strongly associated with decreased triglyceride levels.     

Gastrointestinal helminths found in the three freshwater turtles (<Emphasis Type="Italic">Erymnochelys madagascariensis,Pelomedusa subrufa</Emphasis> and <Emphasis Type="Italic">Pelusios castanoides</Emphasis>) from Ankarafantsika National Park,Madagascar

Summary We conducted a survey of the presence, prevalence and diversity of gastrointestinal helminths in faecal samples and stomach contents of three turtle species, — Erymnochelys madagascariensis (Chelonia: Podocnemididae), Pelomedusa subrufa and Pelusios castanoides (Chelonia: Pelomedusidae), — from several localities in Madagascar. Four nematode species were detected: Atractis chabaudi, Camallanus chelonius, Falcaustra pelusios, and Spiroxys sp. E. madagascariensis, with all four species, had the greatest helminth diversity. A. chabaudi was the community’s core species, whereas Spiroxys sp. was a satellite species. Only two species (A. chabaudi and Spiroxys sp.) were found in P. subrufa and only one, Spiroxys sp., in P. castanoides. These are the first helminthological data on E. madagascariensis, one of the most threatened freshwater turtles in the world.     

Genetic association studies of obesity in Africa: a systematic review

Obesity is increasing in Africa, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within Africa. MEDLINE and EMBASE were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within Africa mostly through the candidate gene approach. Polymorphisms in genes such as ACE, ADIPOQ, ADRB2, AGRP, AR, CAPN10, CD36, C7orf31, DRD4, FTO, MC3R, MC4R, SGIP1 and LEP were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome‐wide association studies (GWAS) elsewhere, only FTO and MC4R polymorphisms showed significant associations with obesity in black South Africans, Nigerians and Ghanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within Africa. There has been recent progress in describing the genetic architecture of obesity among populations within Africa. This effort needs to be sustained via GWAS studies.     

Species of the nematode genus Amidostomum Railliet and Henry, 1909 in aquatic birds in the Netherlands

Summary The presence of gizzard worms belonging to the genus Amidostomum was studied in birds in the Netherlands during the period 1975–2003. Amidostomum acutum was found in Anatidae: Anas acuta, A. clypeata, A. crecca, A. penelope, A. platyrynchos, A. strepera, Aythya ferina, Ay. fuligula, Ay. marila, Bucephala clangula, Melanitta fusca, M. nigra, Tadorna tadorna, Somateria mollissima and Recurvirostra avocetta. No Amidostomum species were found in the following three species of Mergini: Mergus albellus, M. merganser and M. serrator. Amidostomum anseris was seen in Anser albifrons, A. fabalis, Branta bernicla and Branta leucopsis. Amidostomum cygni was detected in Cygnus bewickii and Cygnus olor, while Amidostomum fulicae was found in Fulica atra. The prevalence is only given for bird species where ten or more individuals had been investigated: Anas platyrhynchos (n = 14): 21.4 %; Melanitta nigra (n = 12): 91.7 %; Somateria mollissima (n = 117): 100 %; Anser albifrons (n = 11): 100 % and Cygnus olor (n = 10): 60 %. Based on the present results, much more attention should be paid to the systematics, the epidemiological pattern and the pathogenicity of worms of this genus.     

Life span alteration after irradiation in Drosophila melanogaster strains with mutations of Hsf and Hsps

The life span alteration after γ-irradiation and/or paraquat treatment in Drosophila in wild type strain Canton-S and strains with mutations of heat shock factor (1–4 alleles) and heat shock proteins (Hsp70Ba ³⁰⁴ , Hsp83 ^e6A , Hsp22 ^EY09909 , Hsp67Bb ^EY099099 ) was investigated. Chronic low-dose rate γ-irradiation (0.017 and 0.17 cGy/h) on pre-imago stages was used as a priming dose (absorbed doses were 4 and 40 cGy). Paraquat, a free radical inducing agent, was a challenging factor (20 mM for 1 day). It was shown that chronic irradiation led to adaptive response in both sexes except homozygous males and females with mutations of Hsf ⁴ and Hsp70Ba ³⁰⁴ . The gender-specific differences in stress response were discovered in wild type strain Canton-S, Hsp22 ^EY09909 Hsp67Bb ^EY09909 homozygotes and Hsp83 ^e6A heterozygotes: the adaptive response persisted in males, but not in females. Thus, Drosophila Hsp and Hsf mutation homozygotes did not demonstrate the adaptive response in the majority of cases, implying an important role of those genes in radiation hormesis and adaptation to stresses.     

Determinants of tidal flow volume loop indices in neonates and children with and without asthma

The tidal flow volume (TFV) loop ratios of (1) time to peak flow (tPTEF ) to total expiratory time (tE ) [tPTEF /tE ] and (2) volume to peak flow (VPTEF ) to expired volume (VE ) [VPTEF /VE ] are reported to decrease with age in early life, and to decrease in subjects with obstructive airways disease (OAD). However, the mechanisms behind these changes are not well known. Thus, we reanalyzed data from 24 healthy neonates (mean birthweight: 3.49 kg ± 0.42 kg (SD)), 26 presently asymptomatic asthmatic children (age: 33 ± 21 months), and 26 controls (age: 34 ± 19 months) to elucidate what is responsible for the changes in these ratios in health and disease. Lung function was measured by TFV loops (SensorMedics 2600) at 1 hour of life and on the following day in the neonates, and before and after inhaled nebulized salbutamol (0.05 mg/kg) in the asthmatics and their controls. The observed decreases in mean tPTEF /tE and VPTEF /VE from 1 hour to 1 day of life (neonates) were entirely due to increased tE and VE , respectively secondary to a decrease in respiratory rate (P = 0.03). In asthmatics (young children), the decreased baseline tPTEF /tE and VPTEF /VE were due to lower tPTEF and VPTEF , with no significant differences in tE e and VE in asthmatics and controls. The improved ratios in asthmatic children following inhalation of a bronchodilator were mainly due to increased tPTEF and VPTEF . Our observations point out the importance of evaluating both tPTEF and either tPTEF /tE or VPTEF /VE when attempting to differentiate between changes in ratios that are related to age versus changes that reflect underlying obstructive airways disease. Pediatr. Pulmonol. 1997; 24:391–396. © 1997 Wiley-Liss, Inc.     

Laboratory evaluation and prognostication among adults and children with CEBPA-mutant acute myeloid leukemia

CEBPA-mutant acute myeloid leukemia (AML) encompasses clinically and biologically distinct subtypes of AML in both adults and children. CEBPA-mutant AML may occur with monoallelic (moCEBPA) or biallelic (biCEBPA) mutations, which can be somatic or germline, with each entity impacting prognosis in unique ways. BiCEBPA AML is broadly associated with a favorable prognosis, but differences in the type and location of CEBPA mutations as well as the presence of additional leukemogenic mutations can lead to heterogeneity in survival. Concurrent FLT3-ITD mutations have a well-documented negative effect on survival in adult biCEBPA AML, whereas support for a negative prognostic effect of mutations in TET2, DNMT3A, WT1, CSF3R, ASXL1, and KIT is mixed. NPM1 and GATA2 mutations may have a positive prognostic impact. MoCEBPA AML has similar survival outcomes compared to AML with wild-type CEBPA, and risk stratification is determined by other cytogenetic and molecular findings. Germline CEBPA mutations may lead to familial biCEBPA AML after acquisition of second somatic CEBPA mutation, with variable penetrance and age. BiCEBPA AML in children is likely a favorable-risk diagnosis as it is in adults, but the role of a single CEBPA mutation and the impact of concurrent leukemogenic mutations are not clear in this population. Laboratory evaluation of the CEBPA gene includes PCR-based fragment-length analysis, Sanger sequencing, and next-generation sequencing. Phenotypic analysis using multiparameter flow cytometry can also provide additional data in evaluating CEBPA, helping to assess for the likelihood of mutation presence.     

The prevalence of ay and ad subtypes of the hepatitis B surface antigen in Belgium

Summary Subtyping in various groups of persons positive for hepatitis B surface antigen gave the following results: Among asymptomatic blood donors (healthy carriers) subtypead was found in 20, subtypeay in 24. Among symptomatic patients with acute hepatitis Bad was found in 25,ay in 29. Among patients of an institution for the mentally retardedad was found in 9,ay in 23. Among patients of a geriatric institutionay was found in 9; among medical personnel of the same geriatric institutionay was found in 3 persons. Among symphilis patientsad was found in 6,ay in 29; and in patients of a dialysis centreay was found in 6. These data show that neither subtype is really dominant in Belgium.

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Vorkommen der Hepatitis-B-Oberflächenantigen-Subtypen ay und ad in Belgien

Zusammenfassung Die Bestimmung der Subtypen an verschiedenen Personengruppen mit positivem Hepatitis-B-Oberflächenantigen erbrachte folgende Ergebnisse: Unter asymptomatischen Blutspendern (gesunde Träger) wurde der Subtypad bei 20, der Subtypay bei 24 festgestellt. In einer Gruppe symptomatischer Patienten mit akuter Hepatitis B wurdead bei 25 unday bei 29 ermittelt. Patienten einer Anstalt für geistig Behinderte wiesenad in 9 Fällen unday in 23 Fällen auf. Unter den Patienten einer geriatrischen Klinik wurdeay bei 9 Personen festgestellt, desgleichen bei 3 Personen des ärztlichen Personal derselben geriatrischen Klinik. Bei syphilitischen Patienten wurdead in 6 Fällen unday in 29 Fällen ermittelt. Unter den Patienten eines Dialysezentrums fand sichay in 6 Fällen. Diese Ergebnisse zeigen, daß keiner der beiden Subtypen in Belgien wirlich dominiert.