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Article ; Online: Large-for-gestational-age (LGA) neonate predicts a 2.5-fold increased odds of neonatal hypoglycaemia in women with type 1 diabetes.

Yamamoto, Jennifer M / Kallas-Koeman, Melissa M / Butalia, Sonia / Lodha, Abhay K / Donovan, Lois E

Diabetes/metabolism research and reviews

2017 Volume 33, Issue 1

Abstract: Objective: The objective of the study is to assess the impact of maternal glycaemic control and large-for-gestational-age (LGA) infant size on the risk of developing neonatal hypoglycaemia in offspring of women with type 1 diabetes and to determine ... ...

Abstract	Objective: The objective of the study is to assess the impact of maternal glycaemic control and large-for-gestational-age (LGA) infant size on the risk of developing neonatal hypoglycaemia in offspring of women with type 1 diabetes and to determine possible predictors of neonatal hypoglycaemia and LGA. Research methods and design: This retrospective cohort study evaluated pregnancies in 161 women with type 1 diabetes mellitus at a large urban centre between 2006 and 2010. Mean trimester A Results: Hypoglycaemia occurred in 36.6% of neonates. There was not a linear association between trimester specific A Conclusions: Large-for-gestational-age imparts a 2.5-fold increased odds of hypoglycaemia in neonates of women with type 1 diabetes and may be a better predictor of neonatal hypoglycaemia than maternal glycaemic control. Our data suggest that LGA neonates of women with type 1 diabetes should prompt increased surveillance for neonatal hypoglycaemia and that the presence of optimum maternal glycaemic control should not reduce this surveillance. Copyright © 2016 John Wiley & Sons, Ltd.
MeSH term(s)	Adult ; Body Size ; Diabetes Mellitus, Type 1/physiopathology ; Diabetes, Gestational/physiopathology ; Female ; Fetal Macrosomia/complications ; Follow-Up Studies ; Gestational Age ; Humans ; Hypoglycemia/etiology ; Infant, Newborn ; Male ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, Second ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2017-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1470192-3
ISSN	1520-7560 ; 1520-7552
ISSN (online)	1520-7560
ISSN	1520-7552
DOI	10.1002/dmrr.2824
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Article ; Online: Rare causes of calcitriol-mediated hypercalcemia: a case report and literature review.

Kallas, Melissa / Green, Francis / Hewison, Martin / White, Christopher / Kline, Gregory

The Journal of clinical endocrinology and metabolism

2010 Volume 95, Issue 7, Page(s) 3111–3117

Abstract: Context: Calcitriol-mediated hypercalcemia resulting from elevated extrarenal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase) activity has not previously been described in giant cell polymyositis.: Case: We report an unusual case of ... ...

Abstract	Context: Calcitriol-mediated hypercalcemia resulting from elevated extrarenal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase) activity has not previously been described in giant cell polymyositis. Case: We report an unusual case of hypercalcemia due to disseminated granulomatous disease in a 62-yr-old woman with profound proximal muscle weakness and weight loss. She was initially diagnosed with vitamin D deficiency myopathy with a low serum 25-hydroxyvitamin D; serum calcium at this time was low-normal. Vitamin D(3) 3000 IU daily was prescribed. One month later, blood work showed new hypercalcemia and hypercalciuria with normalized 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D was high-normal, despite a suppressed PTH, undetectable PTHrP, and essentially normal renal function. Her hypercalcemia resolved, and her strength improved only after prednisone was added to bisphosphonate therapy. Two weeks later, she died from acute congestive heart failure. Methods and results: Autopsy revealed a disseminated giant cell myositis affecting skeletal, cardiac, and gastrointestinal smooth muscle. Immunohistochemistry localized 1alpha-hydroxylase to the inflammatory infiltrates in skeletal and cardiac muscle. Evidence: A review of English publications in Medline and Embase, including a reference search of retrieved articles, revealed that calcitriol-mediated hypercalcemia has been described in over 30 conditions, most of which are granulomatous in nature, ranging from inflammatory conditions and foreign body exposures to infections and neoplasms. Conclusions: Hypercalcemia resulting from autonomous 1alpha-hydroxylase activity may be unmasked by low-dose vitamin D supplementation and should not be excluded from the differential diagnosis of nonparathyroid causes if the serum calcitriol is inappropriately normal, rather than frankly elevated.
MeSH term(s)	Calcitriol/blood ; Cholecalciferol/therapeutic use ; Fatal Outcome ; Female ; Heart Failure/etiology ; Humans ; Hypercalcemia/blood ; Hypercalcemia/diagnosis ; Hypercalcemia/etiology ; Middle Aged ; Neurologic Examination ; Polymyositis/blood ; Polymyositis/complications ; Polymyositis/diagnosis ; Vitamin D Deficiency/complications ; Vitamin D Deficiency/drug therapy
Chemical Substances	Cholecalciferol (1C6V77QF41) ; Calcitriol (FXC9231JVH)
Language	English
Publishing date	2010-07
Publishing country	United States
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2009-2673
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Article ; Online: Insulin pump use in pregnancy is associated with lower HbA1c without increasing the rate of severe hypoglycaemia or diabetic ketoacidosis in women with type 1 diabetes.

Kallas-Koeman, Melissa M / Kong, Jason M / Klinke, Jennifer A / Butalia, Sonia / Lodha, Abhay K / Lim, Ken I / Duan, Qiuli M / Donovan, Lois E

Diabetologia

2014 Volume 57, Issue 4, Page(s) 681–689

Abstract: Aims/hypothesis: The aim of this study was to compare glycaemic control and maternal-fetal outcomes in women with type 1 diabetes managed on insulin pumps compared with multiple daily injections of insulin (MDI).: Methods: In a retrospective study, ... ...

Abstract	Aims/hypothesis: The aim of this study was to compare glycaemic control and maternal-fetal outcomes in women with type 1 diabetes managed on insulin pumps compared with multiple daily injections of insulin (MDI). Methods: In a retrospective study, glycaemic control and outcomes of 387 consecutive pregnancies in women with type 1 diabetes who attended specialised clinics at three centres 2006-2010 were assessed. Results: Women using insulin pumps (129/387) were older and had a longer duration of diabetes, more retinopathy, smoked less in pregnancy, and had more preconception care (p < 0.01 for each). Among 113 pregnancies >20 weeks' gestation in women on insulin pumps and 218 in women on MDI, there was a significant difference in HbA1c in the first trimester (mean HbA1c 6.90 ± 0.71% (52 ± 7.8 mmol/mol) vs 7.60 ± 1.38% (60 ± 15.1 mmol/mol), p < 0.001), which persisted until the third trimester (mean HbA1c 6.49 ± 0.52% (47 ± 5.7 mmol/mol) vs 6.81 ± 0.85% (51 ± 9.3 mmol/mol), p = 0.002). Rates of diabetic ketoacidosis were similar in women on insulin pumps vs MDI (1.8% vs 3.0%, p = 0.72). Despite lower HbA1c, women on insulin pumps did not have an increased incidence of severe hypoglycaemia (8.0% vs 7.6%, p = 0.90) or more weight gain (16.3 ± 8.7 vs 15.2 ± 6.2 kg, p = 0.18). More large-for-gestational-age infants in the pump group (55.0% vs 39.2%, p = 0.007) may have resulted from confounding by parity. Conclusions/interpretation: In this large multicentre study, women using insulin pumps in pregnancy had lower HbA1c without increased risk of severe hypoglycaemia or diabetic ketoacidosis but no improvement in other pregnancy outcomes. This information can help inform care providers and patients about the glycaemic effectiveness and safety of insulin pumps in pregnancy.
MeSH term(s)	Adult ; Diabetes Mellitus, Type 1/drug therapy ; Diabetes Mellitus, Type 1/metabolism ; Diabetic Ketoacidosis/epidemiology ; Diabetic Ketoacidosis/metabolism ; Female ; Glycated Hemoglobin A/metabolism ; Humans ; Hypoglycemia/epidemiology ; Hypoglycemia/metabolism ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/therapeutic use ; Insulin/administration & dosage ; Insulin/therapeutic use ; Insulin Infusion Systems/adverse effects ; Male ; Pregnancy ; Retrospective Studies ; Young Adult
Chemical Substances	Glycated Hemoglobin A ; Hypoglycemic Agents ; Insulin
Language	English
Publishing date	2014-01-17
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-014-3163-6
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Article ; Online: CD4+ CD25+ Foxp3+ regulatory T cells, dendritic cells, and circulating cytokines in uncomplicated malaria: do different parasite species elicit similar host responses?

Gonçalves, Raquel M / Salmazi, Karina C / Santos, Bianca A N / Bastos, Melissa S / Rocha, Sandra C / Boscardin, Sílvia B / Silber, Ariel M / Kallás, Esper G / Ferreira, Marcelo U / Scopel, Kézia K G

Infection and immunity

2010 Volume 78, Issue 11, Page(s) 4763–4772

Abstract: Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key ... ...

Abstract	Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4(+) CD25(+) Foxp3(+) Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123(+)), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.
MeSH term(s)	Adult ; Animals ; CD4 Antigens/metabolism ; Cytokines/blood ; Dendritic Cells/immunology ; Female ; Forkhead Transcription Factors/metabolism ; Host-Parasite Interactions/immunology ; Humans ; Interleukin-2 Receptor alpha Subunit/metabolism ; Lymphocyte Activation ; Malaria, Falciparum/immunology ; Malaria, Falciparum/parasitology ; Malaria, Vivax/immunology ; Malaria, Vivax/parasitology ; Male ; Middle Aged ; Plasmodium falciparum/immunology ; Plasmodium falciparum/physiology ; Plasmodium vivax/immunology ; Plasmodium vivax/physiology ; Species Specificity ; T-Lymphocytes, Regulatory/immunology ; Young Adult
Chemical Substances	CD4 Antigens ; Cytokines ; FOXP3 protein, human ; Forkhead Transcription Factors ; IL2RA protein, human ; Interleukin-2 Receptor alpha Subunit
Language	English
Publishing date	2010-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.00578-10
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Article ; Online: Dengue Virus Evades AAV-Mediated Neutralizing Antibody Prophylaxis in Rhesus Monkeys.

Magnani, Diogo M / Ricciardi, Michael J / Bailey, Varian K / Gutman, Martin J / Pedreño-Lopez, Núria / Silveira, Cassia G T / Maxwell, Helen S / Domingues, Aline / Gonzalez-Nieto, Lucas / Su, Qin / Newman, Ruchi M / Pack, Melissa / Martins, Mauricio A / Martinez-Navio, José M / Fuchs, Sebastian P / Rakasz, Eva G / Allen, Todd M / Whitehead, Stephen S / Burton, Dennis R /

Gao, Guangping / Desrosiers, Ronald C / Kallas, Esper G / Watkins, David I

Molecular therapy : the journal of the American Society of Gene Therapy

2017 Volume 25, Issue 10, Page(s) 2323–2331

Abstract: Development of vaccines against mosquito-borne Flaviviruses is complicated by the occurrence of antibody-dependent enhancement (ADE), which can increase disease severity. Long-term delivery of neutralizing antibodies (nAbs) has the potential to ... ...

Abstract	Development of vaccines against mosquito-borne Flaviviruses is complicated by the occurrence of antibody-dependent enhancement (ADE), which can increase disease severity. Long-term delivery of neutralizing antibodies (nAbs) has the potential to effectively block infection and represents an alternative to vaccination. The risk of ADE may be avoided by using prophylactic nAbs harboring amino acid mutations L234A and L235A (LALA) in the immunoglobulin G (IgG) constant region. Here, we used recombinant adeno-associated viruses (rAAVs) to deliver the anti-dengue virus 3 (DENV3) nAb P3D05. While the administration of rAAV-P3D05-rhesus immunoglobulin G1 (rhIgG1)-LALA to rhesus macaques engendered DENV3-neutralizing activity in serum, it did not prevent infection. The emergence of viremia following DENV3 challenge was delayed by 3-6 days in the rAAV-treated group, and replicating virus contained the envelope mutation K64R. This neutralization-resistant variant was also confirmed by virus outgrowth experiments in vitro. By delivering P3D05 with unmutated Fc sequences, we further demonstrated that DENV3 also evaded wild-type nAb prophylaxis, and serum viral loads appeared to be higher in the presence of low levels of unmutated P3D05-rhIgG1. Our study shows that a vectored approach for long-term delivery of nAbs with the LALA mutations is promising, but prophylaxis using a single nAb is likely insufficient at preventing DENV infection and replication.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Dengue Virus/immunology ; Dependovirus/genetics ; Enzyme-Linked Immunosorbent Assay ; Female ; Macaca mulatta ; Male
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2017-07-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2017.06.020
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Zs.A 5640: Show issues

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Article: CD4⁺ CD25⁺ Foxp3⁺ Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

Gonçalves, Raquel M / Salmazi, Karina C / Santos, Bianca A.N / Bastos, Melissa S / Rocha, Sandra C / Boscardin, Sílvia B / Silber, Ariel M / Kallás, Esper G / Ferreira, Marcelo U / Scopel, Kézia K.G

Infection and immunity. 2010 Nov., v. 78, no. 11

2010

Abstract	Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4⁺ CD25⁺ Foxp3⁺ Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123⁺), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.
Keywords	Plasmodium falciparum ; T-lymphocytes ; dendritic cells ; human diseases ; immunity ; indigenous species ; interleukin-10 ; malaria ; models ; parasites ; pathogenesis ; patients ; tumor necrosis factor-alpha
Language	English
Size	p. 4763-4772.
Publishing place	American Society for Microbiology
Document type	Article
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Large-for-gestational-age (LGA) neonate predicts a 2.5-fold increased odds of neonatal hypoglycaemia in women with type 1 diabetes.

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Article ; Online: Rare causes of calcitriol-mediated hypercalcemia: a case report and literature review.

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Article ; Online: Insulin pump use in pregnancy is associated with lower HbA1c without increasing the rate of severe hypoglycaemia or diabetic ketoacidosis in women with type 1 diabetes.

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Article ; Online: CD4+ CD25+ Foxp3+ regulatory T cells, dendritic cells, and circulating cytokines in uncomplicated malaria: do different parasite species elicit similar host responses?

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Article ; Online: Dengue Virus Evades AAV-Mediated Neutralizing Antibody Prophylaxis in Rhesus Monkeys.

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Article: CD4⁺ CD25⁺ Foxp3⁺ Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

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