Browsing by Subject "SERUM"

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  • Junkkari, Reija; Simojoki, Heli; Heiskanen, Minna-Liisa; Pelkonen, Sinikka; Sankari, Satu; Tulamo, Riitta-Mari; Mykkanen, Anna (2017)
    Background: Newly weaned horses in Finland are often moved to unheated loose housing systems in which the weanlings have free access to a paddock and a shelter. This practice is considered to be good for the development of young horses. The daily temperatures can stay below -20 degrees C in Finland for several consecutive weeks during the winter season. However, the effect of unheated housing in a cold climatic environment on the respiratory health of weanlings under field conditions has not been studied before. This investigation was an observational field-study comprising 60 weanlings among 11 different voluntary participant rearing farms in Finland. Weanlings were either kept in unheated loose housing systems (n = 36) or in stables (n = 24) and were clinically examined on two separate occasions 58 days apart in cold winter conditions. Results: The odds of clinical respiratory disease were lower in the older foals(log(e) days); OR = 0.009, P = 0.044). The plasma fibrinogen concentration was higher when the available space (m(2)/weanling) in the sleeping hall was smaller (P = 0.014) and it was lower when the sleeping hall was not insulated (P = 0.010). The plasma fibrinogen concentrations at the second examination were lower with a body condition score above 3 (P = 0.070). Standardbreds kept in loose housing systems had a lower body condition score than Finnhorses or Standardbreds kept in stables at both examinations (P = 0.026 and P = 0.007, respectively). Haemoglobin level was lower in weanlings in loose housing systems compared to their counterparts at the first examination (P = 0.037). Finnhorses had higher white blood cell count than Standardbreds at first (P = 0.002) and at the second examination (P = 0.001). Conclusions: Keeping weanling horses in cold loose housing systems does not seem to increase the occurrence of respiratory disease, but special attention should be focused on ventilation, air quality and feeding-practices. Our field study data suggest it might be advantageous to keep Standardbred foals born late in the season in a stable over the Finnish winter.
  • Hytönen, Marjo K.; Lohi, Hannes (2019)
    Hairlessness is a breed-specific feature selected for in some dog breeds but a rare abnormality in some others such as Scottish Deerhounds (SD). In SDs, the affected puppies are born with sparse hair but lose it within the first 2months leaving the dogs completely hairless. The previous studies have implicated variants in FOXI3 and SGK3 in hairlessness; however, the known variants do not explain hairlessness in all breeds such as SDs. We investigated the genetic cause in 66 SDs, including a litter with two hairless dogs. We utilized a combined approach of genome-wide homozygosity mapping and whole-genome sequencing of a hairless SD followed by recessive filtering according to a recessive model against 340 control genomes. Only two homozygous-coding variants were discovered in the homozygosity regions, including a 1-bp insertion in exon 2 of SGK3. This results in a predicted frameshift and very early truncation (49/490 amino acids) of the SGK3 protein. Additional screening of the recessive variant demonstrated a full segregation with the hairlessness and a 12% carrier frequency in the SD breed. The variant was not found in the related Irish Wolfhound breed. This study identifies the second hairless variant in the SGK3 gene in dogs and further highlights its role as a candidate gene for androgen-independent hair loss or alopecia in human.
  • Motazacker, Mahdi M.; Pirhonen, Juho; van Capelleveen, Julian C.; Weber-Boyvat, Marion; Kuivenhoven, Jan Albert; Shah, Saundarya; Hovingh, G. Kees; Metso, Jari; Li, Shiqian; Ikonen, Elina; Jauhiainen, Matti; Dallinga-Thie, Geesje M.; Olkkonen, Vesa M. (2016)
    Background and aims: Among subjects with high-density-lipoprotein cholesterol (HDL-C) below the 1st percentile in the general population, we identified a heterozygous variant OSBPL1A p.C39X encoding a short truncated protein fragment that co-segregated with low plasma HDL-C. Methods: We investigated the composition and function of HDL from the carriers and non-carriers and studied the properties of the mutant protein in cultured hepatocytes. Results: Plasma HDL-C and apolipoprotein (apo) A-I were lower in carriers versus non-carriers, whereas the other analyzed plasma components or HDL parameters did not differ. Sera of the carriers displayed a reduced capacity to act as cholesterol efflux acceptors (p <0.01), whereas the cholesterol acceptor capacity of their isolated HDL was normal. Fibroblasts from a p.C39X carrier showed reduced cholesterol efflux to lipid-free apoA-I but not to mature HDL particles, suggesting a specific defect in ABCA1-mediated efflux pathway. In hepatic cells, GFP-OSBPL1A partially co-localized in endosomes containing fluorescent apoA-I, suggesting that OSBPL1A may regulate the intracellular handling of apoA-I. The GFP-OSBPL1A-39X mutant protein remained in the cytosol and failed to interact with Rab7, which normally recruits OSBPL1A to late endosomes/lysosomes, suggesting that this mutation represents a loss-of-function. Conclusions: The present work represents the first characterization of a human OSBPL1A mutation. Our observations provide evidence that a familial loss-of-function mutation in OSBPL1A affects the first step of the reverse cholesterol transport process and associates with a low HDL-C phenotype. This suggests that rare mutations in OSBPL genes may contribute to dyslipidemias. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Hepojoki, Satu; Nurmi, Visa; Vaheri, Antti; Hedman, Klaus; Vapalahti, Olli; Hepojoki, Jussi (2014)
  • Simonen, P.; Li, S.; Chua, N. K.; Lampi, A-M; Piironen, V.; Lommi, J.; Sinisalo, J.; Brown, A. J.; Ikonen, E.; Gylling, H. (2020)
    Background We have earlier reported that amiodarone, a potent and commonly used antiarrhythmic drug increases serum desmosterol, the last precursor of cholesterol, in 20 cardiac patients by an unknown mechanism. Objective Here, we extended our study to a large number of cardiac patients of heterogeneous diagnoses, evaluated the effects of combining amiodarone and statins (inhibitors of cholesterol synthesis at the rate-limiting step of hydroxy-methyl-glutaryl CoA reductase) on desmosterol levels and investigated the mechanism(s) by which amiodarone interferes with the metabolism of desmosterol using in vitro studies. Methods and Results We report in a clinical case-control setting of 236 cardiac patients (126 with and 110 without amiodarone treatment) that amiodarone medication is accompanied by a robust increase in serum desmosterol levels independently of gender, age, body mass index, cardiac and other diseases, and the use of statins. Lipid analyses in patient samples taken before and after initiation of amiodarone therapy showed a systematic increase of desmosterol upon drug administration, strongly arguing for a direct causal link between amiodarone and desmosterol accumulation. Mechanistically, we found that amiodarone resulted in desmosterol accumulation in cultured human cells and that the compound directly inhibited the 24-dehydrocholesterol reductase (DHCR24) enzyme activity. Conclusion These novel findings demonstrate that amiodarone blocks the cholesterol synthesis pathway by inhibiting DHCR24, causing a robust accumulation of cellular desmosterol in cells and in the sera of amiodarone-treated patients. It is conceivable that the antiarrhythmic potential and side effects of amiodarone may in part result from inhibition of the cholesterol synthesis pathway.
  • Korhonen, Kati V. M.; Savolainen-Peltonen, Hanna; Mikkola, Tomi S.; Tiitinen, Aila E.; Unkila-Kallio, Leila S. (2016)
    Objectives: Many in vitro fertilization (IVF) complications are inflammatory by nature, some of which are even life-threatening. We evaluated the response of C-reactive protein (CRP) in IVF complications, especially in early and late ovarian hyperstimulation syndrome (OHSS), to support clinical decision making in gynecological emergency policlinics. Study design: In a prospective two-year study at Helsinki University Hospital, Finland, we recruited patients with IVF complications including moderate or severe OHSS (n = 47 patients: 36 early and 14 late OHSS cases), or other IVF complications (n = 13). As controls, we recruited women in an uncomplicated IVF cycle (n = 27). Serial blood samples (CRP, blood count, platelets, albumin, estradiol, creatinine, and electrolytes) were collected from patients upon admission to the emergency polyclinic and during and after treatment on the ward, and from the controls prior, during, and after the IVF protocol. All samples were categorized according to oocyte pick-up (OPU). The statistics included comparisons between and within the study groups, and receiver-operating characteristic (ROC) curve analysis for diagnostic accuracy of CRP for early OHSS at emergency polyclinics. Results: On admission, CRP did not differentiate OHSS from other IVF complications, but CRP was higher in early (median 21; IQR 8-33 mg/L) than in late (6; 3-9 mg/L, p = 0.001) OHSS. In ROC analysis for CRP (12 mg/L), the area under the curve (AUC) was 0.74 (p = 0.001) with sensitivity of 69% and specificity of 71% for early OHSS. CRP was significantly higher (28; 10-46 mg/L) in patients with early OHSS two days after oocyte pick-up (OPU) than in the controls (5; Conclusions: Early OHSS associates with a distinct rise in CRP level beyond that induced by uncomplicated oocyte pick-up, whereas the CRP levels in late OHSS are comparable to those in the control cycles. CRP identifies, but cannot distinguish IVF complications. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Nerenz, Robert D.; Yarbrough, Melanie L.; Stenman, Ulf-Hakan; Gronowski, Ann M. (2016)
    Objective: Elevated concentrations of hCG beta core fragment (hCG beta cf) are known to cause false-negative results in qualitative urine pregnancy test devices, but the pattern of urinary hCG beta cf during normal pregnancy has not been well characterized. Here, we evaluate the relationship between urine hCG, hCG beta cf, and hCG free beta subunit (hCG beta) during pregnancy. Design and methods: Banked second trimester urine specimens from 100 pregnant women were screened for high concentrations of hCG beta cf using a qualitative point-of-care device known to demonstrate false-negative results in the presence of elevated hCG beta cf concentrations. Additional first and third trimester specimens from the same pregnancy were obtained from 10 women who generated negative/faint positive results, 5 women who generated intermediate positive results, and 10 women who generated strong positive results on the point-of care device. Intact hCG, hCG beta cf, hCG beta, and specific gravity were quantified in these 75 specimens. Results: Urinary hCG beta cf concentrations were greater than intact hCG concentrations at all times. A strong correlation (r(2) = 0.70) was observed between urine intact hCG and hCG beta cf concentrations. A poor correlation was observed between specific gravity and intact hCG (r(2) = 0.32), hCG beta (r(2) = 0.32), and hCG beta cf (r(2) = 0.32). The highest hCG beta cf concentrations were observed between 10 and 16 weeks gestation but individual women demonstrated very different patterns of hCG beta cf excretion. Conclusions: Urine specimens with elevated hCG beta cf are frequently encountered during pregnancy but hCG beta cf excretion patterns are unpredictable. Manufacturers and clinicians must appreciate that hCG beta cf is the major immunoreactive component in urine during pregnancy and must design and interpret qualitative urine hCG test results accordingly. (C) 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
  • Piltonen, Terhi T.; Giacobini, Paolo; Edvinsson, Asa; Hustad, Steinar; Lager, Susanne; Morin-Papunen, Laure; Tapanainen, Juha S.; Sundström-Poromaa, Inger; Arffman, Riikka K. (2019)
    Objective: To investigate plasma antimullerian hormone (AMH) concentration and its relation to steroid hormone levels in pregnant women with polycystic ovary syndrome (PCOS) and controls at term. Design: Case-control study. Setting: University-affiliated hospital. Patient(s): A total of 74 pregnant women at term: 25 women with PCOS (aged 31.6 +/- 3.9 years [mean +/- standard deviation], body mass index 24.0 +/- 3.9 kg/m2, mean gestational length 279 +/- 9 days) and 49 controls (aged 31.7 +/- 3.3 years, body mass index 24.0 +/- 3.3 kg/m2, mean gestational length 281 +/- 9 days). Intervention(s): None. Main Outcome Measure(s): Plasma AMH and steroid hormone levels. Result(s): Antimullerian hormone, T, and androstenedione levels were higher in women with PCOS at term compared with controls, whereas estrogen and P levels were similar. The differences were pronounced in women carrying a female fetus. Testosterone and AMH levels correlated positively in both groups, but E2 levels only in women with PCOS. Conclusion(s): Pregnant women with PCOS present with elevated AMH and androgen levels even at term, suggesting a hormonal imbalance during PCOS pregnancy. Differences were detected especially in pregnancies with a female fetus, raising the question of whether female pregnancies are more susceptible to AMH and steroid hormone actions. (C) Copyright (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the American Society for Reproductive Medicine. This is an open access article under the CC BY-NC-ND license (
  • Williams, Monique; Valayannopoulos, Vassili; Altassan, Ruqaiah; Chung, Wendy K.; Heijboer, Annemieke C.; Keng, Wei Teik; Lapatto, Risto; McClean, Patricia; Mulder, Margot F.; Tylki-Szymanska, Anna; Walenkamp, Marie-Jose E.; Alfadhel, Majid; Alakeel, Hajar; Salomons, Gajja S.; Eyaid, Wafaa; Wamelink, Mirjam M. C. (2019)
    BackgroundTransaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation. MethodsWe performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations on blood of 14 patients. Results and conclusionsMost patients (n =22) had an early-onset presentation (prenatally or before 1 month of age); 12 patients had a late-onset presentation (3 months to 9 years). Main presenting symptoms were intrauterine growth restriction, dysmorphic facial features, congenital heart disease, anemia, thrombocytopenia, and hepato(spleno)megaly. An older sib of two affected patients was asymptomatic until the age of 9 years, and only after molecular diagnosis was hepatomegaly noted. In some patients, there was gonadal dysfunction with low levels of testosterone and secondary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) abnormalities later in life. This overview provides information that can be helpful for managing patients and counseling families regarding prognosis. Diagnostic guidelines, possible genotype-phenotype correlations, treatment options, and pathophysiological disease mechanisms are proposed.
  • Felin, Elina; Näreaho, Anu; Fredriksson-Ahomaa, Maria (2017)
    Toxoplasmosis is a globally distributed protozoal zoonosis. Pigs are considered an important reservoir of Toxoplasma gondii and pork a major infection source of human toxoplasmosis. ELISA methods are commonly used diagnostic tools for detecting Toxoplasma infections. They are also used for slaughterhouse-based serological monitoring of toxoplasmosis in pigs to identify positive farms. The methods used are non-standardised with varying sensitivity and specificity. In our study, four commercial ELISA tests for the detection of Toxoplasma antibodies in the meat juice of slaughter pigs were compared with a modified agglutination test (MAT) as a reference. The cut-off values of the ELISA tests provided by the manufacturer varied between 0.20 and 0.50, and clearly influenced prevalence. The sensitivity of tests I, II and III varied between 96.4 and 78.6. Sensitivity was unacceptably low (3.6) for test IV (cut-off=0.30). Tests I, II and III had the highest accuracy and the best agreement with the reference test when a cut-off of 0.30 was used. Test II and III showed very good agreement (K=0.92 and 0.84, respectively) with the MAT. A very strong correlation (Pearson correlation >0.89) was observed between the S/P values of tests I, II and III. Our results demonstrate that the test and cut-off value used influence the results of the apparent seroprevalence studies. (C) 2017 Elsevier B.V. All rights reserved.
  • Murto, Tiina; Yngve, Agneta; Svanberg, Agneta Skoog; Altmae, Signe; Salumets, Andres; Wanggren, Kjell; Stavreus-Evers, Anneli (2017)
    Background: Folate has been discussed in relation to fertility among women, but studies on women under treatment for infertility are lacking. Objective: The objective of this study was to investigate folic acid supplement use and folate status among women under treatment for infertility (hereafter infertile) and fertile women also in regard to socioeconomic and lifestyle factors. Design: Lifestyle and dietary habits, and use of dietary supplements were assessed using a questionnaire. Blood samples were obtained for analysis of folate status. 24-hour recall interviews were also performed. Results: Highly educated, employed and infertile women were most prone to using folic acid supplements. The infertile women had a significantly better folate status than the fertile women. Folate status did not correlate with socioeconomic or lifestyle factors. The infertile women were physically more active, smoked less and were employed. Our questionnaire data had only fair agreement with the data from 24-hour recalls, but the folate status data was clearly correlated to our questionnaire results. Conclusions: Infertile women were most prone to using folic acid supplements and had better folate status than the controls. High educational and employment status were found to be key factors for high compliance to the recommended use folic acid supplements.
  • Hirvonen, Eveliina; Stepanov, Mikhael; Kilpeläinen, Maritta; Lindqvist, Ari; Laitinen, Tarja (2019)
    Introduction: Smoking has a significant impact on the development and progression of asthma and chronic obstructive pulmonary disease (COPD). Self-reported questionnaires and structured interviews are usually the only way to study patients' smoking history. In this study, we aim to examine the consistency of the responses of asthma and COPD patients to repeated standardised questions on their smoking habits over the period of 10 years. Methods: The study population consisted of 1329 asthma and 959 COPD patients, who enrolled in the study during years 2005-2007. A follow-up questionnaire was mailed to the participants 1, 2, 4, 6, 8, and 10 years after the recruitment. Results: Among the participants who returned three or more questionnaires (N = 1454), 78.5 % of the patients reported unchanged smoking status (never smoker, ex-smoker or current smoker) across the time. In 4.5% of the answers, the reported smoking statuses were considered unreliable/conflicting (first never smoker and, later, smoker or ex-smoker). The remainder of the patients changed their status from current smoker to ex-smoker and vice versa at least once, most likely due to struggling with quitting. COPD patients were more frequently heavy ex- or current smokers compared to the asthma group. The intraclass coefficient correlations between self-reported starting (0.85) and stopping (0.94) years as well as the consumption of cigarettes (0.74) over time showed good reliability among both asthma and COPD patients. Conclusion: Self-reported smoking data among elderly asthma and COPD patients over a 10-year follow-up is reliable. Pack years can be considered a rough estimate for their comprehensive consumption of tobacco products over time. We also observed that the questionnaire we used was not designed for dynamic changes in smoking which are rather common among heavy smokers especially when the follow-up time is several years, as in our study.
  • Kerola, Anna; Lohi, Jouko; Heikkilä, Päivi; Mutanen, Annika; Jalanko, Hannu; Pakarinen, Mikko P. (2019)
    Background: Pathogenesis of progressive liver fibrosis in biliary atresia after successful portoenterostomy remains unclear. We related hepatic expression of transforming growth factor beta (TGF-beta) superfamily cytokines to histologic liver injury after successful portoenterostomy. Methods: Enrolled in our study were 28 patients with biliary atresia who had liver biopsies obtained during and after successful portoenterostomy, which normalized serum bilirubin ( Results: After median follow-up of 3.0 years, histologic cholestasis resolved, whereas fibrosis had progressed only in isolated biliary atresia. Liver protein expression of transforming growth factor beta 1 and connective tissue growth factor (P Conclusion: These findings support a central role of transforming growth factor beta superfamily in mediating continuing liver fibrogenesis after successful portoenterostomy. Transforming growth factor beta pathway cytokines responded divergently to clearance of jaundice, which was reflected by differential progression of fibrosis between syndromic and isolated patients. (C) 2018 Elsevier Inc. All rights reserved.
  • Zhang, Xue; Viitala, Tapani; Harjumäki, Riina; Kartal-Hodzic, Alma; Valle-Delgado, Juan Jose; Österberg, Monika (2021)
    The development of in vitro cell models that mimic cell behavior in organs and tissues is an approach that may have remarkable impact on drug testing and tissue engineering applications in the future. Plant based, chemically unmodified cellulose nanofibrils (CNF) hydrogel is a natural, abundant, and biocompatible material that has attracted great attention for biomedical applications, in particular for threedimensional cell cultures. However, the mechanisms of cell-CNF interactions and factors that affect these interactions are not yet fully understood. In this work, multi-parametric surface plasmon resonance (SPR) was used to study how the adsorption of human hepatocellular carcinoma (HepG2) cells on CNF films is affected by the different proteins and components of the cell medium. Both human recombinant laminin 521 (LN-521, a natural protein of the extracellular matrix) and poly -L-lysine (PLL) adsorbed on CNF films and enhanced the attachment of HepG2 cells. Cell medium components (glucose and amino acids) and serum proteins (fetal bovine serum, FBS) also adsorbed on both bare CNF and on protein-coated CNF substrates. However, the adsorption of FBS hindered the attachment of HepG2 cells to LN-521and PLLcoated CNF substrates, suggesting that serum proteins blocked the formation of laminin-integrin bonds and decreased favorable PLL-cell electrostatic interactions. This work sheds light on the effect of different factors on cell attachment to CNF, paving the way for the utilization and optimization of CNF-based materials for different tissue engineering applications. (C) 2020 The Authors. Published by Elsevier Inc.
  • Lassenius, Mariann I.; Ahola, Aila J.; Harjutsalo, Valma; Forsblom, Carol; Groop, Per-Henrik; Lehto, Markku (2016)
    Bacterial lipopolysaccharides (LPS), potent inducers of inflammation, have been associated with chronic metabolic disturbances. Obesity is linked to dyslipidemia, increased body adiposity, and endotoxemia. We investigated the cross-sectional relationships between serum LPS activity and body adiposity as well as inflammation in 242 subjects with type 1 diabetes. Body fat distribution was measured by DXA and serum LPS activity by the limulus amebocyte lysate end-point assay. Since no interaction between visceral fat mass and sex was observed, data were pooled for the subsequent analyses. LPS was independently associated with visceral fat mass, when adjusted for traditional risk factors (age, sex, kidney status, hsCRP, insulin sensitivity). In the multivariate analysis, serum LPS activity and triglyceride concentrations had a joint effect on visceral fat mass, independent of these factors alone. A combination of high LPS and high hsCRP concentrations was also observed in those with the largest visceral fat mass. In conclusion, high serum LPS activity levels were associated with visceral fat mass in subjects with type 1 diabetes strengthening its role in the development of central obesity, inflammation and insulin resistance.
  • Savolainen-Peltonen, Hanna; Vihma, Veera; Wang, Feng; Turpeinen, Ursula; Hämäläinen, Esa; Haanpää, Mikko; Leidenius, Marjut; Tikkanen, Matti J.; Mikkola, Tomi S. (2018)
    Circulating estrogens fluctuate during the menstrual cycle but it is not known whether this fluctuation is related to local hormone levels in adipose tissue. We analyzed estrogen concentrations and gene expression of estrogen-regulating enzymes in breast subcutaneous adipose tissue in premenopausal women with (n = 11) and without (n = 17) estrogen receptor-positive breast cancer. Estrone (E-1) was the predominant estrogen in premenopausal breast adipose tissue, and E-1 and mRNA expression of CYP19A1 in adipose tissue correlated positively with BMI. Adipose tissue estradiol (E-2) concentrations fluctuated during the menstrual cycle, similarly to the serum concentrations. In women with breast cancer median adipose tissue E-1 (1519 vs. 3244, p <.05) and E-2 (404 vs. 889 pmol/kg, p <.05) levels were lower in the follicular than in the luteal phase whereas in control women no significant differences were observed. In the follicular phase, mRNA expressions of HSD17B1 (median 0.06; interquartile range 0.05-0.07 vs. 0.17; 0.03-0.2, p = .010) and CYP19A1 (0.08; 0.07-0.14 vs. 0.22; 0.09-0.54, p = .025) were lower in women with breast cancer than in controls. In conclusion, the changes in adipose tissue E-1 and E-2 concentrations and the estrogen-regulating CYP19A1 and HSD17B1 during the menstrual cycle may be related to dysfunctional local estrogen metabolism in women with breast cancer.
  • Niinisto, Sari; Takkinen, Hanna-Mari; Erlund, Iris; Ahonen, Suvi; Toppari, Jorma; Ilonen, Jorma; Veijola, Riitta; Knip, Mikael; Vaarala, Outi; Virtanen, Suvi M. (2017)
    Aims/hypothesis We investigated the association of early serum fatty acid composition with the risk of type 1 diabetes-associated autoimmunity. Our hypothesis was that fatty acid status during infancy is related to type 1 diabetes-associated autoimmunity and that long-chain n-3 fatty acids, in particular, are associated with decreased risk. Methods We performed a nested case-control analysis within the Finnish Type 1 Diabetes Prediction and Prevention Study birth cohort, carrying HLA-conferred susceptibility to type 1 diabetes (n = 7782). Serum total fatty acid composition was analysed by gas chromatography in 240 infants with islet autoimmunity and 480 control infants at the age of 3 and 6 months. Islet autoimmunity was defined as repeated positivity for islet cell autoantibodies in combination with at least one of three selected autoantibodies. In addition, a subset of 43 infants with primary insulin autoimmunity (i.e. those with insulin autoantibodies as the first autoantibody with no concomitant other autoantibodies) and a control group (n = 86) were analysed. A third endpoint was primary GAD autoimmunity defined as GAD autoantibody appearing as the first antibody without other concomitant autoantibodies (22 infants with GAD autoimmunity; 42 infants in control group). Conditional logistic regression was applied, considering multiple comparisons by false discovery rate <0.05. Results Serum fatty acid composition differed between breastfed and non-breastfed infants, reflecting differences in the fatty acid composition of the milk. Fatty acids were associated with islet autoimmunity (higher serum pentadecanoic, palmitic, palmitoleic and docosahexaenoic acids decreased risk; higher arachidonic: docosahexaenoic and n-6: n-3 acid ratios increased risk). Furthermore, fatty acids were associated with primary insulin autoimmunity, these associations being stronger (higher palmitoleic acid, cis-vaccenic, arachidonic, docosapentaenoic and docosahexaenoic acids decreased risk; higher a-linoleic acid and arachidonic: docosahexaenoic and n-6: n-3 acid ratios increased risk). Moreover, the quantity of breast milk consumed per day was inversely associated with primary insulin autoimmunity, while the quantity of cow's milk consumed per day was directly associated. Conclusions/interpretation Fatty acid status may play a role in the development of type 1 diabetes-associated autoimmunity. Fish-derived fatty acids may be protective, particularly during infancy. Furthermore, fatty acids consumed during breastfeeding may provide protection against type 1 diabetes-associated autoimmunity. Further studies are warranted to clarify the independent role of fatty acids in the development of type 1 diabetes.
  • Jäntti, Toni; Tarvasmäki, Tuukka; Harjola, Veli-Pekka; Parissis, John; Pulkki, Kari; Sionis, Alessandro; Silva-Cardoso, Jose; Kober, Lars; Banaszewski, Marek; Spinar, Jindrich; Fuhrmann, Valentin; Tolonen, Jukka; Carubelli, Valentina; diSomma, Salvatore; Mebazaa, Alexandre; Lassus, Johan; CardShock Investigators (2017)
    Cardiogenic shock (CS) is a cardiac emergency often leading to multiple organ failure and death. Assessing organ dysfunction and appropriate risk stratification are central for the optimal management of these patients. The purpose of this study was to assess the prevalence of abnormal liver function tests (LFTs), as well as early changes of LFTs and their impact on outcome in CS. We measured LFTs in 178 patients in CS from serial blood samples taken at 0 hours, 12 hours, and 24 hours. The associations of LFT abnormalities and their early changes with all-cause 90-day mortality were estimated using Fisher's exact test and Cox proportional hazards regression analysis. Baseline alanine aminotransferase (ALT) was abnormal in 58% of the patients, more frequently in nonsurvivors. Abnormalities in other LFTs analyzed (alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin) were not associated with short-term mortality. An increase in ALT of >20% within 24 hours (AALT>+20%) was observed in 24% of patients. AALT>+20% was associated with a more than 2-fold increase in mortality compared with those with stable or decreasing ALT (70% and 28%, p +20% was associated with increased 90-day mortality independent of other known" risk factors. In conclusion, an increase in ALT in the initial phase was seen in 1/4 of patients in CS and was independently associated with 90-day mortality. This finding suggests that serial ALT measurements should be incorporated in the clinical assessment of patients in CS. (C) 2017 Elsevier Inc. All rights reserved.
  • Hepojoki, Jussi; Cabrera, Luz E.; Hepojoki, Satu; Bellomo, Carla; Kareinen, Lauri; Andersson, Leif C.; Vaheri, Antti; Mäkelä, Satu; Mustonen, Jukka; Vapalahti, Olli; Martinez, Valeria; Strandin, Tomas (2021)
    In humans, orthohantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). An earlier study reported that acute Andes virus HPS caused a massive and transient elevation in the number of circulating plasmablasts with specificity towards both viral and host antigens suggestive of polyclonal B cell activation. Immunoglobulins (Igs), produced by different B cell populations, comprise heavy and light chains; however, a certain amount of free light chains (FLCs) is constantly present in serum. Upregulation of FLCs, especially clonal species, associates with renal pathogenesis by fibril or deposit formations affecting the glomeruli, induction of epithelial cell disorders, or cast formation in the tubular network. We report that acute orthohantavirus infection increases the level of Ig FLCs in serum of both HFRS and HPS patients, and that the increase correlates with the severity of acute kidney injury in HFRS. The fact that the kappa to lambda FLC ratio in the sera of HFRS and HPS patients remained within the normal range suggests polyclonal B cell activation rather than proliferation of a single B cell clone. HFRS patients demonstrated increased urinary excretion of FLCs, and we found plasma cell infiltration in archival patient kidney biopsies that we speculate to contribute to the observed FLC excreta. Analysis of hospitalized HFRS patients' peripheral blood mononuclear cells showed elevated plasmablast levels, a fraction of which stained positive for Puumala virus antigen. Furthermore, B cells isolated from healthy donors were susceptible to Puumala virus in vitro, and the virus infection induced increased production of Igs and FLCs. The findings propose that hantaviruses directly activate B cells, and that the ensuing intense production of polyclonal Igs and FLCs may contribute to acute hantavirus infection-associated pathological findings. Author summary Orthohantaviruses are globally spread zoonotic pathogens, which can cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) with significant burden to human health. The pathogenesis mechanisms of orthohantavirus-caused diseases are not known in detail; however, excessive immune response towards the virus with concomitant pathological effects against host tissues appears to be a contributing factor. Here we report an increase of free immunoglobulin (Ig) light chains (FLCs), components required to make complete Ig molecules, in blood of acute HFRS and HPS. Samples collected during acute HFRS demonstrated increased FLCs levels in the urine and blood of patients hospitalized due the disease. Furthermore, the FLC levels positively correlated with markers of acute kidney injury. In addition, our results show that orthohantaviruses can infect and activate B cells to produce FLCs as well as whole Igs, which provides a mechanistic explanation of the increased FLC levels in patients. Taken together, our results suggest that aberrant antibody responses might play a role in the pathogenesis of orthantavirus infections.
  • Vihma, Veera; Heinonen, Sini; Naukkarinen, Jussi; Kaprio, Jaakko; Rissanen, Aila; Turpeinen, Ursula; Hämäläinen, Esa; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Mikkola, Tomi S.; Tikkanen, Matti J.; Pietiläinen, Kirsi H. (2018)
    Objective: Obesity may alter serum steroid concentrations and metabolism. We investigated this in healthy young women with increased body fat and their leaner co-twin sisters. Design: Age and genetic background both strongly influence serum steroid levels and body composition. This is a cross-sectional study of 13 female monozygotic twin pairs (age, 23-36 years), ten of which were discordant for body mass index (median difference in body weight between the co-twins, 19 kg). Methods: We determined body composition by dual energy X-ray absorptiometry and magnetic resonance imaging, serum androgens by liquid chromatography-tandem mass spectrometry, and mRNA expression of genes in subcutaneous adipose tissue and adipocytes. Results: The heavier women had lower serum dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) (P <0.05 for all) compared to their leaner co-twins with no differences in serum testosterone or androstenedione levels. Serum DHEA correlated inversely with %body fat (r = -0.905, P = 0.002), and DHT positively with SHBG (r = 0.842, P = 0.002). In adipose tissue or adipocytes, expressions of STS (steroid sulfatase) and androgen-related genes were significantly higher in the heavier compared to the leaner co-twin, and within pairs, correlated positively with adiposity but were not related to serum androgen levels. None of the serum androgen or SHBG levels correlated with indices of insulin resistance. Conclusions: Serum DHEA levels were best predicted by %body fat, and serum DHT by SHBG. These or other serum androgen concentrations did not reflect differences in androgen-related genes in adipose tissue. General or intra-abdominal adiposity were not associated with increased androgenicity in young women.