The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform

Heikki Hyöty - One of the best experts on this subject based on the ideXlab platform.

  • Maternal Enterovirus Infection as a Risk Factor for Type 1 Diabetes in the Exposed Offspring
    Diabetes Care, 2012
    Co-Authors: Hanna Viskari, Sisko Tauriainen, Riitta Veijola, Olli Simell, Mikael Knip, Heini Huhtala, Jorma Ilonen, Heljä-marja Surcel, Heikki Hyöty
    Abstract:

    OBJECTIVE Maternal Enterovirus Infections during pregnancy have been linked to an increased risk of type 1 diabetes in the offspring. The aim of this study was to evaluate this association in a unique series of pregnant mothers whose child progressed to clinical type 1 diabetes. RESEARCH DESIGN AND METHODS Maternal and in utero Enterovirus Infections were studied in 171 offspring who presented with type 1 diabetes before the age of 11 years and in 316 control subjects matched for date and place of birth, gender, and HLA-DQ risk alleles for diabetes. Acute Enterovirus Infections were diagnosed by increases in Enterovirus IgG and IgM in samples taken from the mother at the end of the first trimester of pregnancy and cord blood samples taken at delivery. RESULTS Signs of maternal Enterovirus Infection were observed in altogether 19.3% of the mothers of affected children and in 12.0% of the mothers of control children ( P = 0.038). This difference was seen in different HLA risk groups and in both genders of the offspring, and it was unrelated to the age of the child at the diagnosis of diabetes or the age of the mother at delivery. CONCLUSIONS These results suggest that an Enterovirus Infection during pregnancy is not a major risk factor for type 1 diabetes in childhood but may play a role in some susceptible subjects.

  • type 1 diabetes is associated with Enterovirus Infection in gut mucosa
    Diabetes, 2012
    Co-Authors: Maarit Oikarinen, Sisko Tauriainen, Sami Oikarinen, Teemu Honkanen, Pekka Collin, Immo Rantala, Markku Maki, Katri Kaukinen, Heikki Hyöty
    Abstract:

    Enterovirus Infections have been linked to type 1 diabetes in several studies. Enteroviruses also have tropism to pancreatic islets and can cause β-cell damage in experimental models. Viral persistence has been suspected to be an important pathogenetic factor. This study evaluates whether gut mucosa is a reservoir for Enterovirus persistence in type 1 diabetic patients. Small-bowel mucosal biopsy samples from 39 type 1 diabetic patients, 41 control subjects, and 40 celiac disease patients were analyzed for the presence of Enterovirus using in situ hybridization (ISH), RT-PCR, and immunohistochemistry. The presence of virus was compared with inflammatory markers such as infiltrating T cells, HLA-DR expression, and transglutaminase 2–targeted IgA deposits. Enterovirus RNA was found in diabetic patients more frequently than in control subjects and was associated with a clear inflammation response in the gut mucosa. Viral RNA was often detected in the absence of viral protein, suggesting defective replication of the virus. Patients remained virus positive in follow-up samples taken after 12 months’ observation. The results suggest that a large proportion of type 1 diabetic patients have prolonged/persistent Enterovirus Infection associated with an inflammation process in gut mucosa. This finding opens new opportunities for studying the viral etiology of type 1 diabetes.

  • interaction of Enterovirus Infection and cow s milk based formula nutrition in type 1 diabetes associated autoimmunity
    Diabetes-metabolism Research and Reviews, 2012
    Co-Authors: Johanna Lempainen, Heikki Hyöty, Sisko Tauriainen, Outi Vaarala, Miia Makela, Hanna Honkanen, Jane Marttila, Riitta Veijola, Olli Simell, Mikael Knip
    Abstract:

    Background Enteral virus Infections and early introduction of cow's milk (CM)-based formula are among the suggested triggers of type 1 diabetes (T1D)-associated autoimmunity, although studies on their role have remained contradictory. Here, we aimed to analyse whether interactions between these factors might clarify the controversies. Materials The study population comprised 107 subjects developing positivity for at least two T1D-associated autoantibodies and 446 control subjects from the Finnish diabetes prediction and prevention cohort. Enterovirus, rotavirus, adenovirus, respiratory syncytial virus and bovine insulin-binding antibodies were analysed from prospective serum samples at 3–24 months of age. Data on infant cow's milk exposure were available for 472 subjects: 251 subjects were exposed to cow's milk before 3 months of age and 221 subjects later in infancy. Results Signs of an Enterovirus Infection by 12 months of age were associated with the appearance of autoimmunity among children who were exposed to cow's milk before 3 months of age. Cox regression analysis revealed a combined effect of Enterovirus Infection and early cow's milk exposure for the development of ICA and any of the biochemically defined autoantibodies (p = 0.001), of IAA (p = 0.002), GADA (p = 0.001) and IA-2A (p = 0.013). Conclusions The effect of Enterovirus Infection on the appearance of T1D-associated autoimmunity seems to be modified by exposure to cow's milk in early infancy suggesting an interaction between these factors. Moreover, these results provide an explanation for the controversial findings obtained when analysing the effect of any single one of these factors on the appearance of T1D-associated autoimmunity. Copyright © 2011 John Wiley & Sons, Ltd.

  • Enterovirus Infection and progression from islet autoimmunity to type 1 diabetes the diabetes and autoimmunity study in the young daisy
    Diabetes, 2010
    Co-Authors: Lars C Stene, Heikki Hyöty, Sami Oikarinen, Katherine Barriga, Jill M Norris, Georgeanna J Klingensmith, John C Hutton, Henry A Erlich, George S Eisenbarth, Marian Rewers
    Abstract:

    OBJECTIVE To investigate whether Enterovirus Infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies. RESEARCH DESIGN AND METHODS Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3–6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5′ noncoding region, detecting essentially all Enterovirus serotypes. RESULTS Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical type 1 diabetes in the sample interval following detection of enteroviral RNA in serum (three diabetes cases diagnosed among 17 intervals) was significantly increased compared with that in intervals following a negative serum enteroviral RNA test (33 cases diagnosed among 1,064 intervals; hazard ratio 7.02 [95% CI 1.95–25.3] after adjusting for number of autoantibodies). Results remained significant after adjustment for ZnT8-autoantibodies and after restriction to various subgroups. Enteroviral RNA in rectal swabs was not predictive of progression to type 1 diabetes. No evidence for viral persistence was found. CONCLUSIONS This novel observation suggests that progression from islet autoimmunity to type 1 diabetes may increase after an Enterovirus Infection characterized by the presence of viral RNA in blood.

  • detection of Enteroviruses in the intestine of type 1 diabetic patients
    Clinical and Experimental Immunology, 2007
    Co-Authors: Maarit Oikarinen, Sami Oikarinen, Teemu Honkanen, Immo Rantala, Markku Maki, Katri Kaukinen, S Tauriainen, K Vuori, Heikki Hyöty
    Abstract:

    Enterovirus Infections have been diagnosed more frequently in type 1 diabetic patients than in the healthy population, and Enteroviruses have also been found in the pancreas of diabetic patients. Primary replication of the virus occurs in the gut, but there are no previous studies evaluating possible presence of virus in the intestine of diabetic patients. The purpose of this study was to investigate if Enteroviruses can be found in small intestinal tissue of type 1 diabetic patients. Formalin-fixed, paraffin-embedded upper intestinal biopsy samples were analysed for the presence of Enterovirus using in situ hybridization and immunohistochemistry. Enterovirus was detected by in situ hybridization in six (50%) of the type 1 diabetic patients (n = 12) but in none of the control subjects (n = 10, P = 0·015). Immunohistochemistry identified Enterovirus in nine (75%) of the patients and one (10%) control subject (P = 0·004). The presence of the virus was confirmed by reverse transcription–polymerase chain reaction in one of the four patients from whom a frozen and unfixed sample was available. Intestinal morphology was normal in all study subjects. The results suggest that a substantial proportion of type 1 diabetic patients have an ongoing Enterovirus Infection in gut mucosa, possibly reflecting persistent Enterovirus Infection. This observation opens new avenues for further studies on the possible role of Enteroviruses in human type 1 diabetes.

Sami Oikarinen - One of the best experts on this subject based on the ideXlab platform.

  • type 1 diabetes is associated with Enterovirus Infection in gut mucosa
    Diabetes, 2012
    Co-Authors: Maarit Oikarinen, Sisko Tauriainen, Sami Oikarinen, Teemu Honkanen, Pekka Collin, Immo Rantala, Markku Maki, Katri Kaukinen, Heikki Hyöty
    Abstract:

    Enterovirus Infections have been linked to type 1 diabetes in several studies. Enteroviruses also have tropism to pancreatic islets and can cause β-cell damage in experimental models. Viral persistence has been suspected to be an important pathogenetic factor. This study evaluates whether gut mucosa is a reservoir for Enterovirus persistence in type 1 diabetic patients. Small-bowel mucosal biopsy samples from 39 type 1 diabetic patients, 41 control subjects, and 40 celiac disease patients were analyzed for the presence of Enterovirus using in situ hybridization (ISH), RT-PCR, and immunohistochemistry. The presence of virus was compared with inflammatory markers such as infiltrating T cells, HLA-DR expression, and transglutaminase 2–targeted IgA deposits. Enterovirus RNA was found in diabetic patients more frequently than in control subjects and was associated with a clear inflammation response in the gut mucosa. Viral RNA was often detected in the absence of viral protein, suggesting defective replication of the virus. Patients remained virus positive in follow-up samples taken after 12 months’ observation. The results suggest that a large proportion of type 1 diabetic patients have prolonged/persistent Enterovirus Infection associated with an inflammation process in gut mucosa. This finding opens new opportunities for studying the viral etiology of type 1 diabetes.

  • Enterovirus Infection and progression from islet autoimmunity to type 1 diabetes the diabetes and autoimmunity study in the young daisy
    Diabetes, 2010
    Co-Authors: Lars C Stene, Heikki Hyöty, Sami Oikarinen, Katherine Barriga, Jill M Norris, Georgeanna J Klingensmith, John C Hutton, Henry A Erlich, George S Eisenbarth, Marian Rewers
    Abstract:

    OBJECTIVE To investigate whether Enterovirus Infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies. RESEARCH DESIGN AND METHODS Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3–6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5′ noncoding region, detecting essentially all Enterovirus serotypes. RESULTS Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical type 1 diabetes in the sample interval following detection of enteroviral RNA in serum (three diabetes cases diagnosed among 17 intervals) was significantly increased compared with that in intervals following a negative serum enteroviral RNA test (33 cases diagnosed among 1,064 intervals; hazard ratio 7.02 [95% CI 1.95–25.3] after adjusting for number of autoantibodies). Results remained significant after adjustment for ZnT8-autoantibodies and after restriction to various subgroups. Enteroviral RNA in rectal swabs was not predictive of progression to type 1 diabetes. No evidence for viral persistence was found. CONCLUSIONS This novel observation suggests that progression from islet autoimmunity to type 1 diabetes may increase after an Enterovirus Infection characterized by the presence of viral RNA in blood.

  • detection of Enteroviruses in the intestine of type 1 diabetic patients
    Clinical and Experimental Immunology, 2007
    Co-Authors: Maarit Oikarinen, Sami Oikarinen, Teemu Honkanen, Immo Rantala, Markku Maki, Katri Kaukinen, S Tauriainen, K Vuori, Heikki Hyöty
    Abstract:

    Enterovirus Infections have been diagnosed more frequently in type 1 diabetic patients than in the healthy population, and Enteroviruses have also been found in the pancreas of diabetic patients. Primary replication of the virus occurs in the gut, but there are no previous studies evaluating possible presence of virus in the intestine of diabetic patients. The purpose of this study was to investigate if Enteroviruses can be found in small intestinal tissue of type 1 diabetic patients. Formalin-fixed, paraffin-embedded upper intestinal biopsy samples were analysed for the presence of Enterovirus using in situ hybridization and immunohistochemistry. Enterovirus was detected by in situ hybridization in six (50%) of the type 1 diabetic patients (n = 12) but in none of the control subjects (n = 10, P = 0·015). Immunohistochemistry identified Enterovirus in nine (75%) of the patients and one (10%) control subject (P = 0·004). The presence of the virus was confirmed by reverse transcription–polymerase chain reaction in one of the four patients from whom a frozen and unfixed sample was available. Intestinal morphology was normal in all study subjects. The results suggest that a substantial proportion of type 1 diabetic patients have an ongoing Enterovirus Infection in gut mucosa, possibly reflecting persistent Enterovirus Infection. This observation opens new avenues for further studies on the possible role of Enteroviruses in human type 1 diabetes.

Marian Rewers - One of the best experts on this subject based on the ideXlab platform.

  • Enterovirus Infection and progression from islet autoimmunity to type 1 diabetes the diabetes and autoimmunity study in the young daisy
    Diabetes, 2010
    Co-Authors: Lars C Stene, Heikki Hyöty, Sami Oikarinen, Katherine Barriga, Jill M Norris, Georgeanna J Klingensmith, John C Hutton, Henry A Erlich, George S Eisenbarth, Marian Rewers
    Abstract:

    OBJECTIVE To investigate whether Enterovirus Infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies. RESEARCH DESIGN AND METHODS Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3–6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5′ noncoding region, detecting essentially all Enterovirus serotypes. RESULTS Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical type 1 diabetes in the sample interval following detection of enteroviral RNA in serum (three diabetes cases diagnosed among 17 intervals) was significantly increased compared with that in intervals following a negative serum enteroviral RNA test (33 cases diagnosed among 1,064 intervals; hazard ratio 7.02 [95% CI 1.95–25.3] after adjusting for number of autoantibodies). Results remained significant after adjustment for ZnT8-autoantibodies and after restriction to various subgroups. Enteroviral RNA in rectal swabs was not predictive of progression to type 1 diabetes. No evidence for viral persistence was found. CONCLUSIONS This novel observation suggests that progression from islet autoimmunity to type 1 diabetes may increase after an Enterovirus Infection characterized by the presence of viral RNA in blood.

Harley A. Rotbart - One of the best experts on this subject based on the ideXlab platform.

  • neonatal Enterovirus Infection virology serology and effects of intravenous immune globulin
    Clinical Infectious Diseases, 1995
    Co-Authors: Mark J Abzug, Harry L Keyserling, Myron J Levin, Harley A. Rotbart
    Abstract:

    A prospective study of the virology of and serological responses to Enterovirus Infection in 7 6 neonates (≤2 weeks of life) and their mothers was performed. At study entry, 7 7 neonates did not have detectable serum neutralizing antibody to their own viral isolates, despite the presence of neutralizing antibody in 9 of 1 7 mothers of these infants. Viremia and viruria were demonstrated in 8 and 7 neonates, respectively, with maximal detected titers of 6.3×10 3 50% tissue culture infective dose per mL (TCID 50 ) and 6.8×10 1 TCID 50 /mL, respectively. Viremia was associated with onset of illness in the first 5 days of life, low initial serum neutralization titer, and the presence of echovirus serotypes. Randomized administration of intravenous immune globulin (IVIG; 750 mg/kg) to nine neonates overall modestly increased serum neutralization titers but did not reduce the daily incidence of viremia and viruria compared with that of controls. However, receipt of IVIG containing a neutralization titer of ≥1:800 to the patients'own viral isolates was associated with significantly higher serum neutralization titers and more rapid cessation of viremia and viruria. Future trials of IVIG for neonatal Enterovirus disease should assess the efficacy and safety of higher or repeated doses of this agent and for of IVIG lots selected for their high titers to frequently circulating and for particularly virulent Enterovirus serotypes

  • Diagnosis of neonatal Enterovirus Infection by polymerase chain reaction
    The Journal of Pediatrics, 1995
    Co-Authors: Mark J Abzug, Michael J. Loeffelholz, Harley A. Rotbart
    Abstract:

    Abstract A 5-hour colorimetric polymerase chain reaction (PCR) assay was more sensitive than viral culture in identifying viral Infection in initial serum (13/16 vs 5/16; p = 0.008) and urine (10/16 vs 5/16; p = 0.2) specimens from 16 Enterovirus- infected newborn infants, and remained more sensitive throughout their illnesses. Combined sensitivity of serum and urine PCR was 14 of 16 (88%). Results of all acute-phase PCR assays of serum and urine from four neonates with cultures negative for Enterovirus were also negative. PCR assay of serum and urine facilitates rapid, accurate diagnosis of neonatal Enterovirus Infections. (J PEDIATR 1995;126:447-50)

  • Persistent Enterovirus Infection in Culture-Negative Meningoencephalitis: Demonstration by Enzymatic RNA Amplification
    The Journal of Infectious Diseases, 1990
    Co-Authors: Harley A. Rotbart, John R Kinsella, Richard L. Wasserman
    Abstract:

    : Chronic meningoencephalitis due to Enterovirus Infection can occur in patients with antibody deficiencies. A modified polymerase chain reaction technique demonstrated persistent echovirus 11 Infection in such a patient, despite negative routine viral cultures and negative routine nucleic acid hybridization. Although the sequence of echovirus 11 has not yet been determined, genomic conservation among the Enteroviruses is significant, permitting detection of echovirus 11 with a primer pair and probe derived from Enterovirus serotypes that have been fully sequenced. This study provides the first definitive evidence for the persistence of Enterovirus Infection with negative viral cultures.

Sisko Tauriainen - One of the best experts on this subject based on the ideXlab platform.

  • Maternal Enterovirus Infection as a Risk Factor for Type 1 Diabetes in the Exposed Offspring
    Diabetes Care, 2012
    Co-Authors: Hanna Viskari, Sisko Tauriainen, Riitta Veijola, Olli Simell, Mikael Knip, Heini Huhtala, Jorma Ilonen, Heljä-marja Surcel, Heikki Hyöty
    Abstract:

    OBJECTIVE Maternal Enterovirus Infections during pregnancy have been linked to an increased risk of type 1 diabetes in the offspring. The aim of this study was to evaluate this association in a unique series of pregnant mothers whose child progressed to clinical type 1 diabetes. RESEARCH DESIGN AND METHODS Maternal and in utero Enterovirus Infections were studied in 171 offspring who presented with type 1 diabetes before the age of 11 years and in 316 control subjects matched for date and place of birth, gender, and HLA-DQ risk alleles for diabetes. Acute Enterovirus Infections were diagnosed by increases in Enterovirus IgG and IgM in samples taken from the mother at the end of the first trimester of pregnancy and cord blood samples taken at delivery. RESULTS Signs of maternal Enterovirus Infection were observed in altogether 19.3% of the mothers of affected children and in 12.0% of the mothers of control children ( P = 0.038). This difference was seen in different HLA risk groups and in both genders of the offspring, and it was unrelated to the age of the child at the diagnosis of diabetes or the age of the mother at delivery. CONCLUSIONS These results suggest that an Enterovirus Infection during pregnancy is not a major risk factor for type 1 diabetes in childhood but may play a role in some susceptible subjects.

  • type 1 diabetes is associated with Enterovirus Infection in gut mucosa
    Diabetes, 2012
    Co-Authors: Maarit Oikarinen, Sisko Tauriainen, Sami Oikarinen, Teemu Honkanen, Pekka Collin, Immo Rantala, Markku Maki, Katri Kaukinen, Heikki Hyöty
    Abstract:

    Enterovirus Infections have been linked to type 1 diabetes in several studies. Enteroviruses also have tropism to pancreatic islets and can cause β-cell damage in experimental models. Viral persistence has been suspected to be an important pathogenetic factor. This study evaluates whether gut mucosa is a reservoir for Enterovirus persistence in type 1 diabetic patients. Small-bowel mucosal biopsy samples from 39 type 1 diabetic patients, 41 control subjects, and 40 celiac disease patients were analyzed for the presence of Enterovirus using in situ hybridization (ISH), RT-PCR, and immunohistochemistry. The presence of virus was compared with inflammatory markers such as infiltrating T cells, HLA-DR expression, and transglutaminase 2–targeted IgA deposits. Enterovirus RNA was found in diabetic patients more frequently than in control subjects and was associated with a clear inflammation response in the gut mucosa. Viral RNA was often detected in the absence of viral protein, suggesting defective replication of the virus. Patients remained virus positive in follow-up samples taken after 12 months’ observation. The results suggest that a large proportion of type 1 diabetic patients have prolonged/persistent Enterovirus Infection associated with an inflammation process in gut mucosa. This finding opens new opportunities for studying the viral etiology of type 1 diabetes.

  • interaction of Enterovirus Infection and cow s milk based formula nutrition in type 1 diabetes associated autoimmunity
    Diabetes-metabolism Research and Reviews, 2012
    Co-Authors: Johanna Lempainen, Heikki Hyöty, Sisko Tauriainen, Outi Vaarala, Miia Makela, Hanna Honkanen, Jane Marttila, Riitta Veijola, Olli Simell, Mikael Knip
    Abstract:

    Background Enteral virus Infections and early introduction of cow's milk (CM)-based formula are among the suggested triggers of type 1 diabetes (T1D)-associated autoimmunity, although studies on their role have remained contradictory. Here, we aimed to analyse whether interactions between these factors might clarify the controversies. Materials The study population comprised 107 subjects developing positivity for at least two T1D-associated autoantibodies and 446 control subjects from the Finnish diabetes prediction and prevention cohort. Enterovirus, rotavirus, adenovirus, respiratory syncytial virus and bovine insulin-binding antibodies were analysed from prospective serum samples at 3–24 months of age. Data on infant cow's milk exposure were available for 472 subjects: 251 subjects were exposed to cow's milk before 3 months of age and 221 subjects later in infancy. Results Signs of an Enterovirus Infection by 12 months of age were associated with the appearance of autoimmunity among children who were exposed to cow's milk before 3 months of age. Cox regression analysis revealed a combined effect of Enterovirus Infection and early cow's milk exposure for the development of ICA and any of the biochemically defined autoantibodies (p = 0.001), of IAA (p = 0.002), GADA (p = 0.001) and IA-2A (p = 0.013). Conclusions The effect of Enterovirus Infection on the appearance of T1D-associated autoimmunity seems to be modified by exposure to cow's milk in early infancy suggesting an interaction between these factors. Moreover, these results provide an explanation for the controversial findings obtained when analysing the effect of any single one of these factors on the appearance of T1D-associated autoimmunity. Copyright © 2011 John Wiley & Sons, Ltd.