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Search Results: 1 - 10 of 1427 matches for " Johanna Tommiska "
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Reversible Congenital Hypogonadotropic Hypogonadism in Patients with CHD7, FGFR1 or GNRHR Mutations
Eeva-Maria Laitinen, Johanna Tommiska, Timo Sane, Kirsi Vaaralahti, Jorma Toppari, Taneli Raivio
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039450
Abstract: Background Congenital hypogonadotropic hypogonadism (HH) is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH) have common phenotypic or genotypic features. Methods and Findings Thirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26) or normal sense of smell (nHH; n = 6) were enrolled (age range, 18–61 yrs). The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, WDR11, GNRHR, GNRH1, KISS1R, KISS1, TAC3, TACR3, and LHβ were screened for mutations. Six HH patients (2 KS, 4 nHH) were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21–39 yrs). All had spontaneous testicular growth while on testosterone replacement therapy (TRT). One nHH subject was restarted on TRT due to a decline in serum T. Two reversal variants had a same GNRHR mutation (R262Q), which was accompanied by another GNRHR mutation (R139H or del309F). In addition, both of the KS patients had a mutation in CHD7 (p.Q51X) or FGFR1 (c.91+2T>A). Conclusions Considerable proportion of patients with HH (8% of KS probands) may recover in early adulthood. Spontaneous testicular enlargement during TRT was highly suggestive for reversal of HH. Those with the GNRHR mutation R262Q accompanied by another GNRHR mutation may be prone to reversal, although even patients with a truncating mutation in CHD7 or a splice-site mutation in FGFR1 can recover. We recommend that all adolescents and young adults with congenital HH should be informed on the possibility of reversal.
LIN28B, LIN28A, KISS1, and KISS1R in idiopathic central precocious puberty
Johanna Tommiska, Kaspar S?rensen, Lise Aksglaede, Rosanna Koivu, Lea Puhakka, Anders Juul, Taneli Raivio
BMC Research Notes , 2011, DOI: 10.1186/1756-0500-4-363
Abstract: Thirty girls with ICPP were included in the study. ICPP was defined by pubertal onset before 8 yrs of age, and a pubertal LH response to GnRH testing. The coding regions of LIN28B, LIN28A, KISS1, and KISS1R were sequenced. The missense change in LIN28B was also screened in 132 control subjects.No rare variants were detected in KISS1 or KISS1R in the 30 subjects with ICPP. In LIN28B, one missense change, His199Arg, was found in one subject with ICPP. However, this variant was also detected in one of the 132 controls. No variation in LIN28A was found.We did not find any evidence that mutations in LIN28B or LIN28A would underlie ICPP. In addition, we confirmed that mutations in KISS1 and KISS1R are not a common cause for ICPP.During the last decades, a decline in age at pubertal onset in girls has been reported worldwide [1,2], paralleled by an increase in the incidence of idiopathic central precocious puberty (ICPP) [3]. However, the etiology underlying the precocious reactivation of the hypothalamic-pituitary-gonadal (HPG) axis in girls with ICPP is still largely unresolved. As compared with normal-timed pubertal controls, girls with ICPP have increased adiposity and decreased insulin sensitivity at diagnosis, suggesting a causal link between these metabolic factors and HPG axis programming [4]. However, these metabolic factors may only elicit an early HPG activation in the presence of a susceptible genetic background. Overall, the genetic modulation of pubertal onset most likely arises from the additive effect of multiple genes [5], but also monogenic causes of ICPP probably exist, as cases of familial ICPP have been reported (reviewed in [5]). For example, a 27.5% prevalence of familial ICPP has been reported in one study; the suggested mode of inheritance was autosomal dominant with incomplete sex-dependent penetrance [6].Only few genes have been investigated in mutation screening studies in ICPP. Inactivating mutations in the KISS1R (GPR54) gene cause autosomal r
Incidence, Phenotypic Features and Molecular Genetics of Kallmann Syndrome in Finland
Eeva-Maria Laitinen, Kirsi Vaaralahti, Johanna Tommiska, Elina Eklund, Mari Tervaniemi, Leena Valanne, Taneli Raivio
Orphanet Journal of Rare Diseases , 2011, DOI: 10.1186/1750-1172-6-41
Abstract: Herein, we investigated epidemiological, clinical, and genetic features of KS in Finland.The minimal incidence estimate of KS in Finland was 1:48 000, with clear difference between males (1:30 000) and females (1:125 000) (p = 0.02). The reproductive phenotype of 30 probands (25 men; 5 women) ranged from severe HH to partial puberty. Comprehensive mutation analysis of all 7 known KS genes (KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, and WDR11) in these 30 well-phenotyped probands revealed mutations in KAL1 (3 men) and FGFR1 (all 5 women vs. 4/25 men), but not in other genes.Our results suggest that Finnish KS men harbor mutations in gene(s) yet-to-be discovered with sex-dependent penetrance of the disease phenotype. In addition, some KS patients without CHD7 mutations display CHARGE-syndrome associated phenotypic features (e.g. ear or eye anomalies), possibly implying that, in addition to CHD7, there may be other genes associated with phenotypes ranging from KS to CHARGE.Kallmann syndrome (KS; MIM# 147950), a combination of congenital hypogonadotropic hypogonadism (HH; MIM# 146110) and decreased/absent sense of smell, results from disturbed intrauterine migration of gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode to the hypothalamus [1-3]. Patients with KS usually lack puberty, but the reproductive phenotype may vary from severe hypogonadism (cryptorchidism or micropenis in male infants) to reversal of hypogonadotropism later in life [4,5]. Associated phenotypic features include cleft lip/palate, hearing impairment, dental agenesis, limb anomalies, renal agenesis, and mirror movements [6]. The incidence estimates of KS are scarce and variable, and the condition appears to be 3-5 times more frequent in men [6-8].KS is genetically heterogeneous, and the majority of cases (~60%) present as sporadic cases (only one person affected in the family). In familial KS, autosomal recessive, autosomal dominant, and X-chromosomal recessive inheritance have be
Variants on the promoter region of PTEN affect breast cancer progression and patient survival
Tuomas Heikkinen, Dario Greco, Liisa M Pelttari, Johanna Tommiska, Pia Vahteristo, P?ivi Heikkil?, Carl Blomqvist, Kristiina Aittom?ki, Heli Nevanlinna
Breast Cancer Research , 2011, DOI: 10.1186/bcr3076
Abstract: We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes.All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets.Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer.Hereditary predisposition to breast cancer is caused by variation in multiple genes affecting the cancer risk with varying penetrance. Mutations in the main high penetrance genes BRCA1 and BRCA2 are mostly found in families with multiple breast cancer cases particularly with early onset and with ovarian cancer [1,2], and may also affect breast cancer survival among the mutation carriers [3,4]. Strong familial breast cancer predisposition is also present in rare cancer s
ATM variants and cancer risk in breast cancer patients from Southern Finland
Johanna Tommiska, Laila Jansen, Outi Kilpivaara, Hege Edvardsen, Vessela Kristensen, Anitta Tamminen, Kristiina Aittom?ki, Carl Blomqvist, Anne-Lise B?rresen-Dale, Heli Nevanlinna
BMC Cancer , 2006, DOI: 10.1186/1471-2407-6-209
Abstract: Two common ATM variants, 5557G>A and ivs38-8T>C, previously suggested to associate with bilateral breast cancer, were genotyped in an extensive set of 786 familial and 884 unselected breast cancer cases as well as 708 healthy controls. We also screened the entire coding region and exon-intron boundaries of the ATM gene in 47 familial breast cancer patients and constructed haplotypes of the patients. The identified variants were also evaluated for increased breast cancer risk among additional breast cancer cases and controls.Neither of the two common variants, 5557G>A and ivs38-8T>C, nor any haplotype containing them, was significantly associated with breast cancer risk, bilateral breast cancer or multiple primary cancers in any of the patient groups or subgoups. Three rare missense alterations and one intronic change were each found in only one patient of over 250 familial patients studied and not among controls. The fourth missense alteration studied further was found with closely similar frequencies in over 600 familial cases and controls.Altogether, our results suggest very minor effect, if any, of ATM genetic variants on familial breast cancer in Southern Finland. Our results do not support association of the 5557G>A or ivs38-8T>C variant with increased breast cancer risk or with bilateral breast cancer.The ATM (Ataxia-Telangiectasia Mutated) kinase has an essential role in maintaining genomic integrity. It is a key activator of the cellular responses to DNA double-strand breaks [1]. Mutations in the ATM gene cause ataxia-telangiectasia (A-T) [2], a rare recessive disorder characterized by progressive neurodegeneration, cell cycle checkpoint defects, radiosensitivity and increased risk of cancer, particularly of lymphoid malignancies [3]. As radiation exposure is associated with an increased risk of breast cancer, the function of the ATM protein makes it a good candidate for a role in breast cancer predisposition [4]. The first suggestion that ATM might be a bre
Combined effects of single nucleotide polymorphisms TP53 R72P and MDM2 SNP309, and p53 expression on survival of breast cancer patients
Marjanka K Schmidt, Johanna Tommiska, Annegien Broeks, Flora E van Leeuwen, Laura J Van't Veer, Paul DP Pharoah, Douglas F Easton, Mitul Shah, Manjeet Humphreys, Thilo D?rk, Scarlett A Reincke, Rainer Fagerholm, Carl Blomqvist, Heli Nevanlinna
Breast Cancer Research , 2009, DOI: 10.1186/bcr2460
Abstract: We pooled data from four breast cancer cohorts within the Breast Cancer Association Consortium for which both TP53 R72P and MDM2 SNP309 were genotyped and follow-up was available (n = 3,749). Overall and breast cancer-specific survival analyses were performed using Kaplan-Meier analysis and multivariate Cox's proportional hazards regression models.Survival of patients did not differ by carriership of either germ-line variant, R72P (215G>C) or SNP309 (-410G>T) alone. Immunohistochemical p53 staining of the tumor was available for two cohorts (n = 1,109 patients). Survival was worse in patients with p53-positive tumors (n = 301) compared to patients with p53-negative tumors (n = 808); breast cancer-specific survival: HR 1.6 (95% CI 1.2 to 2.1), P = 0.001. Within the patient group with p53-negative tumors, TP53 rare homozygous (CC) carriers had a worse survival than G-allele (GG/GC) carriers; actuarial breast cancer-specific survival 71% versus 80%, P = 0.07; HR 1.8 (1.1 to 3.1), P = 0.03. We also found a differential effect of combinations of the two germ-line variants on overall survival; homozygous carriers of the G-allele in MDM2 had worse survival only within the group of TP53 C-allele carriers; actuarial overall survival (GG versus TT/TG) 64% versus 75%, P = 0.001; HR (GG versus TT) 1.5 (1.1 to 2.0), P = 0.01. We found no evidence for a differential effect of MDM2 SNP309 by p53 protein expression on survival.The TP53 R72P variant may be an independent predictor for survival of patients with p53-negative tumors. The combined effect of TP53 R72P and MDM2 SNP309 on survival is in line with our a priori biologically-supported hypothesis, that is, the role of enhanced DNA repair function of the TP53 Pro-variant, combined with increased expression of the Mdm2 protein, and thus overall attenuation of the p53 pathway in the tumor cells.Breast cancer outcome may be affected by germ-line variants in genes that play a role in DNA damage control and repair such as TP53 (R72P
An Information-Theoretic Analysis of Genetics, Gender and Age in Cancer Patients
Gurinder Singh Atwal, Raúl Rabadán, Guillermina Lozano, Louise C. Strong, Mari?lle W. G. Ruijs, Marjanka K. Schmidt, Laura J. van't Veer, Heli Nevanlinna, Johanna Tommiska, Kristiina Aittom?ki, Gaelle Bougeard, Thierry Frebourg, Arnold J. Levine, Gareth L. Bond
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001951
Abstract: Germline genetics, gender and hormonal-signaling pathways are all well described modifiers of cancer risk and progression. Although an improved understanding of how germline genetic variants interact with other cancer risk factors may allow better prevention and treatment of human cancer, measuring and quantifying these interactions is challenging. In other areas of research, Information Theory has been used to quantitatively describe similar multivariate interactions. We implemented a novel information-theoretic analysis to measure the joint effect of a high frequency germline genetic variant of the p53 tumor suppressor pathway (MDM2 SNP309 T/G) and gender on clinical cancer phenotypes. This analysis quantitatively describes synergistic interactions among gender, the MDM2 SNP309 locus, and the age of onset of tumorigenesis in p53 mutation carriers. These results offer a molecular and genetic basis for the observed sexual dimorphism of cancer risk in p53 mutation carriers and a model is proposed that suggests a novel cancer prevention strategy for p53 mutation carriers.
Perspectives for Wearable Electronics in Healthcare and Childcare  [PDF]
Johanna Virkki, Pasi Raumonen
E-Health Telecommunication Systems and Networks (ETSN) , 2013, DOI: 10.4236/etsn.2013.23008
Abstract: This paper starts with a literature survey that introduces possibilities of wearable electronics (WE) in different healthcare and childcare applications. Next, 24 personal interviews and an Internet forum survey were conducted in Finland about the use of WE in applications mentioned above. According to the results, most of the people feel positive about clothes used for wireless identification purposes in healthcare and childcare, but when more information about the person is added that can be wirelessly read, the feelings become more negative. Several important points to consider before implementation of WE for healthcare and childcare environments were brought up.
Process Adaption and Modifications of a Nutrient Removing Wastewater Treatment Plant in Sri Lanka Operated at Low Loading Conditions  [PDF]
Johanna Berg, Stig Morling
Materials Sciences and Applications (MSA) , 2013, DOI: 10.4236/msa.2013.45038

The Sri Lankan national water authority, that is The National Water Supply and Drainage Board (NWS&DB) has taken a new wastewater treatment plant into operation at Ja Ela, North of Colombo. The plant has been in operation since September 2011. In April 2012, it was concluded how a test of the aeration efficiency and a performance test should be carried out. The tests have been based on the actual loading of the plant and the analysis results from the daily process control. The evaluation of the aeration efficiency is not reported in this paper. The paper presents the overall performance of the water treatment part of the plant during start-up conditions, from fall 2011 through the first five months of 2012. The results from the operation are found in Table 1. An important circumstance at the plant is the current very low loading in comparison with the design load. This fact has resulted in an introduction of an intermittent mode of the aeration (nitrification) reactor. Based on operation figures, during more than a month (May 2012), it has been possible to give a realistic assessment of the overall performance. The most striking results are summarized as follows: 1) The intermittent operation has enabled an energy efficient operation of the plant. By the introduction of the intermittent aeration, the energy consumption has been reduced by around 75%, compared with the continuous operation mode; 2) The plant performance during the intermittent operation has been improved with respect to virtually all important pollu

Personal Perspectives: Individual Privacy in the IOT  [PDF]
Johanna Virkki, Liquan Chen
Advances in Internet of Things (AIT) , 2013, DOI: 10.4236/ait.2013.32003

The Internet of Things (IOT) is the extension of the Internet to the next level, i.e., bringing the Internet to the real physical world of things. In this research, 22 people working with different aspects of IOT development were interviewed in Finland and in China, in order to investigate their thoughts and personal opinions on the IOT and the individual privacy in the IOT. This paper presents the background of the IOT, interviews and collected answers, as well as highlights of collected free comments.

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