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1.
Orphanet J Rare Dis ; 17(Suppl 1): 170, 2022 04 19.
Article in English | MEDLINE | ID: mdl-35440056

ABSTRACT

Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Dunnigan syndrome is characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome, associated with a risk of metabolic, cardiovascular and muscular complications. Its prevalence, assessed at 1/100.000 in Europe, is probably considerably underestimated. Thorough clinical examination is key to diagnosis. Biochemical testing frequently shows hyperinsulinemia, abnormal glucose tolerance and hypertriglyceridemia. Elevated hepatic transaminases (hepatic steatosis) and creatine phosphokinase, and hyperandrogenism in women, are common. Molecular analysis of the LMNA gene confirms diagnosis and allows for family investigations. Regular screening and multidisciplinary monitoring of the associated complications are necessary. Diabetes frequently develops from puberty onwards. Hypertriglyceridemia may lead to acute pancreatitis. Early atherosclerosis and cardiomyopathy should be monitored. In women, polycystic ovary syndrome is common. Overall, the management of patients with Dunnigan syndrome requires the collaboration of several health care providers. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are described to provide such a support.


Subject(s)
Hypertriglyceridemia , Insulin Resistance , Lipodystrophy, Familial Partial , Lipodystrophy , Pancreatitis , Acute Disease , Female , Humans , Hypertriglyceridemia/complications , Lipodystrophy, Familial Partial/diagnosis , Lipodystrophy, Familial Partial/genetics , Lipodystrophy, Familial Partial/therapy
2.
Diabetes Metab ; 48(3): 101306, 2022 05.
Article in English | MEDLINE | ID: mdl-34813929

ABSTRACT

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 1 , Adult , Blood Glucose , Blood Glucose Self-Monitoring , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Child , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Heart Disease Risk Factors , Humans , Prospective Studies , Risk Factors
3.
Diabetes Metab ; 47(3): 101206, 2021 05.
Article in English | MEDLINE | ID: mdl-33152550

ABSTRACT

Automated closed-loop (CL) insulin therapy has come of age. This major technological advance is expected to significantly improve the quality of care for adults, adolescents and children with type 1 diabetes. To improve access to this innovation for both patients and healthcare professionals (HCPs), and to promote adherence to its requirements in terms of safety, regulations, ethics and practice, the French Diabetes Society (SFD) brought together a French Working Group of experts to discuss the current practical consensus. The result is the present statement describing the indications for CL therapy with emphasis on the idea that treatment expectations must be clearly defined in advance. Specifications for expert care centres in charge of initiating the treatment were also proposed. Great importance was also attached to the crucial place of high-quality training for patients and healthcare professionals. Long-term follow-up should collect not only metabolic and clinical results, but also indicators related to psychosocial and human factors. Overall, this national consensus statement aims to promote the introduction of marketed CL devices into standard clinical practice.


Subject(s)
Diabetes Mellitus, Type 1 , Insulin Infusion Systems , Insulin , Adolescent , Adult , Child , Diabetes Mellitus, Type 1/drug therapy , France , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage
4.
BMC Med ; 16(1): 159, 2018 08 25.
Article in English | MEDLINE | ID: mdl-30143037

ABSTRACT

The original article [1] contains errors in Table 1 affecting some of the presented oligonucleotide sequences and readthrough values in Table 1.

6.
Diabetes Metab ; 44(1): 61-72, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29174479

ABSTRACT

The use by diabetes patients of real-time continuous interstitial glucose monitoring (CGM) or the FreeStyle Libre® (FSL) flash glucose monitoring (FGM) system is becoming widespread and has changed diabetic practice. The working group bringing together a number of French experts has proposed the present practical consensus. Training of professionals and patient education are crucial for the success of CGM. Also, institutional recommendations must pay particular attention to the indications for and reimbursement of CGM devices in populations at risk of hypoglycaemia. The rules of good practice for CGM are the precursors of those that need to be enacted, given the oncoming emergence of artificial pancreas devices. It is necessary to have software combining user-friendliness, multiplatform usage and average glucose profile (AGP) presentation, while integrating glucose and insulin data as well as events. Expression of CGM data must strive for standardization that facilitates patient phenotyping and their follow-up, while integrating indicators of variability. The introduction of CGM involves a transformation of treatment support, rendering it longer and more complex as it also includes specific educational and technical dimensions. This complexity must be taken into account in discussions of organization of diabetes care.


Subject(s)
Blood Glucose Self-Monitoring , Patient Education as Topic , Practice Guidelines as Topic , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/therapy , France , Humans , Retrospective Studies
7.
Diabetes Metab ; 39(2): 174-7, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23206896

ABSTRACT

AIM: Insulin allergy is a rare but serious and challenging condition in patients with type 1 diabetes (T1D). This is a case report of an 8-year-old boy with T1D and an allergy to insulin. CASE REPORT: Three months after being diagnosed with T1D, the patient developed progressive skin reactions to insulin, characterized by small 1.5-cm pruritic wheals at injection sites that persisted for several days. Seven months after diagnosis, he experienced two episodes of generalized urticaria with systemic symptoms that were seen within a few seconds of insulin injection. Examination revealed lipoatrophy of the thighs. Intradermal skin tests were positive for protamine, glargine and lispro. The patient was started on a continuous subcutaneous insulin infusion (CSII) tolerance induction protocol, consisting of a very low basal rate that was progressively increased, with the first bolus given under medical supervision, and was well tolerated for 4 months. After this period of time, the skin wheals reappeared, localized to the infusion sites, but without urticaria or any other generalized reactions. Intradermal skin tests were repeated and were again positive. Serum insulin-specific IgE measured 30 months after the first allergic reactions were positive. After 3 years, pump therapy is ongoing and blood glucose control has remained relatively good (HbA1c 7.6%). CONCLUSION: In T1D children with insulin allergy, CSII can successfully be used to both induce insulin tolerance and allow diabetes insulin therapy, although insulin desensitization cannot always be fully achieved. The induction protocol was easily manageable partly due to the "honeymoon" period that the patient was still in, but it should nonetheless be used even when the patient has higher insulin requirements.


Subject(s)
Diabetes Mellitus, Lipoatrophic/immunology , Diabetes Mellitus, Type 1/immunology , Drug Hypersensitivity/immunology , Hypoglycemic Agents/immunology , Infusions, Subcutaneous/adverse effects , Insulin/immunology , Blood Glucose , Child , Diabetes Mellitus, Lipoatrophic/drug therapy , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/drug therapy , Drug Hypersensitivity/drug therapy , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Insulin/administration & dosage , Insulin/adverse effects , Insulin Infusion Systems , Male , Thigh , Treatment Outcome , Urticaria
8.
Diabetes Metab ; 38(3): 205-16, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22521040

ABSTRACT

AIM: The clinical guidelines reported by the French-Speaking Diabetes Society (Société francophone du diabète) include updated recommendations for preconceptual planning and care in the management of pregnancy in women with type 1 diabetes mellitus (T1DM). METHODS: The working group included diabetologists, as well as an obstetrician, a nurse and a dietician. A review of the literature was performed using PubMed and Cochrane databases. Guidelines published by foreign diabetes societies were also consulted. RESULTS: In women with T1DM, pregnancy increased the risks of hypoglycaemia, diabetic ketoacidosis, pregnancy-induced hypertension, infections and worsening of diabetic microvascular disease. Moreover, T1DM during pregnancy had an impact on the embryo and the fetus, and may have increased the risk of spontaneous miscarriages, malformations, premature births, and fetal and neonatal complications. However, intensive glycaemic control and preconceptual care have been shown to decrease the rate of fetal demise and malformations. Also, the use of insulin analogues during pregnancy is now regarded as safe. Tight glucose control and frequent follow-up are recommended throughout pregnancy in women with T1DM. Their obstetric management should take place in a maternity hospital with an appropriate perinatal environment and in close collaboration with diabetologists. CONCLUSION: Pregnancy planning and adequate management during pregnancy are mandatory for improving the outcomes of women with T1DM.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1/drug therapy , Diabetic Ketoacidosis/drug therapy , Hypoglycemia/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Pregnancy in Diabetics/drug therapy , Abortion, Spontaneous/prevention & control , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Diabetic Ketoacidosis/blood , Diabetic Ketoacidosis/complications , Female , France , Humans , Hypoglycemia/blood , Hypoglycemia/complications , Pregnancy , Premature Birth/prevention & control
9.
Arch Pediatr ; 15(4): 462-8, 2008 Apr.
Article in French | MEDLINE | ID: mdl-18321691

ABSTRACT

The child is an individual in constant development, dependent on his/her parents with whom he interacts everyday to open out, and in particular, to construct a dependable image of his body for growing up comfortably. Announcement of a disease, real traumatism for the whole family, upsets these exchanges and can often induce psychological difficulties masked by the therapeutic somatic stakes placed at the foreground of concerns of each one: child, parents and doctors. The child's stakes are construction of a good image of the body (basis of his own) which can be deteriorated by the disease whatever it is (chronic disease, with relapse or vital prognosis engaged). The family's stakes are the perception of the disease by the parents (distress, culpability, depression) and sibling's reactions (aggressiveness, identification with the sick child, masked depression, functional troubles). Doctor's stakes in the chronic disease is to obtain therapeutic alliance of the child and his family to allow the good progress of the treatments. In front of the chronic disease's reality, it is essential to establish and maintain a multidisciplinary follow up. The child's psychiatrist role will be to take care of the exchanges, and listening among the doctors, the patient and his family are favoured.


Subject(s)
Body Image , Chronic Disease/psychology , Adult , Child , Chronic Disease/classification , Developmental Disabilities/psychology , Female , Humans , Male , Parent-Child Relations , Perception , Physician-Patient Relations , Self Concept
10.
J Immunol ; 165(6): 3301-8, 2000 Sep 15.
Article in English | MEDLINE | ID: mdl-10975847

ABSTRACT

Immunization with peptide or recombinant proteins generally fails to elicit CTL, which are thought to play a key role in the control of virus-infected cells and tumor growth. In this study we show that the nontoxic B subunit of Shiga toxin fused to a tumor peptide derived from the mouse mastocytoma P815 can induce specific CTL in mice without the use of adjuvant. The Shiga B subunit acts as a vector rather than as an adjuvant, because coinjection of the tumor peptide and the B subunit as separate entities does not lead to CTL induction. We also demonstrated that in vitro the B subunit mediates the delivery of various exogenous CD8 T cell epitopes into the conventional MHC class I-restricted pathway, as this process is inhibited by brefeldin A and lactacystin and requires a functional TAP system. In contrast to other nonviral methods for transport of exogenous Ags into the endogenous MHC class I pathway that involve macropinocytosis or phagocytosis, the Shiga B subunit targets this pathway in a receptor-dependent manner, namely via binding to the glycolipid Gb3. Because this receptor is highly expressed on various dendritic cells, it should allow preferential targeting of the Shiga B subunit to these professional APCs. Therefore, the Shiga B subunit appears to represent an attractive vector for vaccine development due to its ability to target dendritic cells and to induce specific CTL without the need for adjuvant.


Subject(s)
Acetylcysteine/analogs & derivatives , Antigen Presentation/genetics , Antigens, Neoplasm/genetics , Bacterial Toxins/immunology , Dendritic Cells/immunology , Histocompatibility Antigens Class I/immunology , Peptides/immunology , Recombinant Fusion Proteins/immunology , T-Lymphocytes, Cytotoxic/immunology , ATP Binding Cassette Transporter, Subfamily B, Member 2 , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/physiology , Acetylcysteine/pharmacology , Animals , Antigen Presentation/drug effects , Antigens, Neoplasm/administration & dosage , Antigens, Neoplasm/immunology , Bacterial Toxins/administration & dosage , Bacterial Toxins/genetics , Bacterial Toxins/metabolism , Brefeldin A/pharmacology , Cytotoxicity, Immunologic/genetics , Dendritic Cells/metabolism , Female , Injections, Intraperitoneal , Intracellular Fluid/immunology , Intracellular Fluid/metabolism , Leukemia L1210 , Lymphocyte Activation/genetics , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Knockout , Ovalbumin/administration & dosage , Ovalbumin/immunology , Ovalbumin/metabolism , Peptides/metabolism , Protein Processing, Post-Translational/drug effects , Protein Processing, Post-Translational/immunology , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/genetics , Sarcoma, Experimental/genetics , Sarcoma, Experimental/immunology , Shiga Toxins , Signal Transduction/genetics , Signal Transduction/immunology , T-Lymphocytes, Cytotoxic/metabolism , Tumor Cells, Cultured
11.
Plant Physiol ; 120(3): 717-26, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10398706

ABSTRACT

Mitochondrial NAD-dependent (IDH) and cytosolic NADP-dependent isocitrate dehydrogenases have been considered as candidates for the production of 2-oxoglutarate required by the glutamine synthetase/glutamate synthase cycle. The increase in IDH transcripts in leaf and root tissues, induced by nitrate or NH4+ resupply to short-term N-starved tobacco (Nicotiana tabacum) plants, suggested that this enzyme could play such a role. The leaf and root steady-state mRNA levels of citrate synthase, acotinase, IDH, and glutamine synthetase were found to respond similarly to nitrate, whereas those for cytosolic NADP-dependent isocitrate dehydrogenase and fumarase responded differently. This apparent coordination occurred only at the mRNA level, since activity and protein levels of certain corresponding enzymes were not altered. Roots and leaves were not affected to the same extent either by N starvation or nitrate addition, the roots showing smaller changes in N metabolite levels. After nitrate resupply, these organs showed different response kinetics with respect to mRNA and N metabolite levels, suggesting that under such conditions nitrate assimilation was preferentially carried out in the roots. The differential effects appeared to reflect the C/N status after N starvation, the response kinetics being associated with the nitrate assimilatory capacity of each organ, signaled either by nitrate status or by metabolite(s) associated with its metabolism.

12.
Proc Natl Acad Sci U S A ; 95(13): 7813-8, 1998 Jun 23.
Article in English | MEDLINE | ID: mdl-9636233

ABSTRACT

In this work, we describe the isolation of a new cDNA encoding an NADP-dependent isocitrate dehydrogenase (ICDH). The nucleotide sequence in its 5' region gives a deduced amino acid sequence indicative of a targeting peptide. However, even if this cDNA clearly encodes a noncytosolic ICDH, it is not possible to say from the targeting peptide sequence to which subcellular compartment the protein is addressed. To respond to this question, we have transformed tobacco plants with a construct containing the entire targeting signal-encoding sequence in front of a modified green fluorescent protein (GFP) gene. This construct was placed under the control of the cauliflower mosaic virus 35S promoter, and transgenic tobacco plants were regenerated. At the same time, and as a control, we also have transformed tobacco plants with the same construct but lacking the nucleotide sequence corresponding to the ICDH-targeting peptide, in which the GFP is retained in the cytoplasm. By optical and confocal microscopy of leaf epiderm and Western blot analyses, we show that the putative-targeting sequence encoded by the cDNA addresses the GFP exclusively into the mitochondria of plant cells. Therefore, we conclude that this cDNA encodes a mitochondrial ICDH.


Subject(s)
Isocitrate Dehydrogenase/isolation & purification , Mitochondria/enzymology , Amino Acid Sequence , Biomarkers , Flow Cytometry , Gene Library , Genetic Markers , Green Fluorescent Proteins , Isocitrate Dehydrogenase/metabolism , Isoenzymes/isolation & purification , Isoenzymes/metabolism , Luminescent Proteins/metabolism , Microscopy, Confocal , Molecular Sequence Data , Plants, Toxic , Nicotiana
13.
Plant Mol Biol ; 30(2): 307-20, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8616254

ABSTRACT

A cDNA which encodes a specific member of the NADP-dependent isocitrate dehydrogenase (ICDH) multi-isoenzyme family has been isolated from a tobacco cell suspension library, and the expression pattern of ICDH transcripts examined in various plant tissues. To assign this cDNA to a specific ICDH isoenzyme, the major, cytosolic ICDH isoenzyme of tobacco leaves (ICDH1) was purified to homogeneity and its N-terminus as well as several tryptic peptides, representing 30% of the protein, were sequenced. The comparison of these amino acid sequences with the deduced protein sequence of the cDNA confirmed that this clone encodes for ICDH1. The total ICDH specific activity and protein content were higher in vascular-enriched tobacco leaf tissue than in deveined (depleted in midrib and first-order veins) leaves. Taking advantage of antibodies raised against either ICDH1 or the chloroplastic ICDH2 isoenzyme from tobacco cell suspensions, an immuno-cytochemical approach indicated that the ICDH1 isoenzyme, located in the cytosolic compartment of tobacco leaf cells, is responsible for this expression pattern. This observation was confirmed by northern blot analyses, using a specific probe obtained from the 3' non-coding region of the ICDH1 cDNA. A comparison of ICDH protein sequences shows a large degree of similarity between eukaryotes (> 60%) but a poor homology is observed when compared to Escherichia coli ICDH (< 20%). However, it was found that the amino acids implicated in substrate binding, deduced from the 3-dimensional structure of the E. coli NADP-ICDH, appear to be conserved in all the deduced eukaryotic ICDH proteins reported until now.


Subject(s)
Cytosol/enzymology , Isocitrate Dehydrogenase/genetics , Isoenzymes/genetics , Nicotiana/genetics , Plants, Toxic , Amino Acid Sequence , Base Sequence , Blotting, Northern , Blotting, Western , Cell Compartmentation , Cloning, Molecular , Conserved Sequence , DNA, Complementary/genetics , Immunohistochemistry , Isocitrate Dehydrogenase/isolation & purification , Molecular Sequence Data , Plant Leaves/enzymology , Plant Leaves/ultrastructure , RNA, Messenger/genetics , RNA, Plant/genetics , Sequence Analysis , Sequence Homology, Amino Acid , Species Specificity , Tissue Distribution , Nicotiana/enzymology
14.
Arch Biochem Biophys ; 323(1): 164-8, 1995 Oct 20.
Article in English | MEDLINE | ID: mdl-7487062

ABSTRACT

The recently isolated full-length NADP-dependent isocitrate dehydrogenase (ICDH) cDNA encoding the tobacco cytosolic isoenzyme has been cloned into the expression vector pET8c and used to transform Escherichia coli strain BL21 (DE3). The recombinant protein was purified to electrophoretic homogeneity and used to raise polyclonal antibodies. Its kinetic properties were found to be identical to those of the cytosolic ICDH isoenzyme purified from tobacco cell cultures. The recombinant and the endogenous bacterial ICDH could be easily distinguished by their different behaviors during anion-exchange column chromatography and immunological response. An incomplete ICDH-encoding cDNA clone, encoding a protein lacking the first 36 amino acids at the N-terminus, was cloned into the expression vector pKK233-2 and used to transform ICDH-lacking E. coli cells (strain 2004). The truncated, recombinant ICDH produced by the bacteria was found to be inactive.


Subject(s)
Escherichia coli/enzymology , Isocitrate Dehydrogenase/metabolism , Nicotiana/enzymology , Plants, Toxic , Amino Acid Sequence , Base Sequence , DNA, Complementary/genetics , DNA, Complementary/isolation & purification , Enzyme Activation , Escherichia coli/genetics , Isocitrate Dehydrogenase/chemistry , Isocitrate Dehydrogenase/genetics , Isocitrate Dehydrogenase/isolation & purification , Molecular Sequence Data , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism
15.
Planta ; 197(2): 324-32, 1995.
Article in English | MEDLINE | ID: mdl-8547818

ABSTRACT

Chloroplastic NADP(+)-malate dehydrogenase (cpMDH, EC 1.1.1.82) is a key enzyme in the carbon-fixation pathway of some C4 plants such as the monocotyledons maize or Sorghum. We have expressed cpMDH from Sorghum vulgare Pers. in transgenic tobacco (Nicotiana tabacum L.) (a dicotyledonous C3 plant) by using a gene composed of the Sorghum cpMDH cDNA under the control of cauliflower mosaic virus 35S promoter. High steady-state levels of cpMDH mRNA were observed in isogenic dihaploid transgenic tobacco lines. Sorghum cpMDH protein was detected in transgenic leaf extracts, where a threefold higher cpMDH activity could be measured, compared with control tobacco leaves. The recombinant protein was identical in molecular mass and in N-terminal sequence to Sorghum cpMDH. The tobacco cpMDH protein which has a distinct N-terminal sequence, could not be detected in transgenic plants. Immunocytochemical analyses showed that Sorghum cpMDH was specifically localized in transgenic tobacco chloroplasts. These data indicate that Sorghum cpMDH preprotein was efficiently synthesized, transported into and processed in tobacco chloroplasts. Thus, C3-C4 photosynthesis specialization or monocotyledon-dicotyledon evolution did not affect the chloroplastic protein-import machinery. The higher levels of cpMDH in transgenic leaves resulted in an increase of L-malate content, suggesting that carbon metabolism was altered by the expression of the Sorghum enzyme.


Subject(s)
Chloroplasts/metabolism , Cotyledon/enzymology , Malate Dehydrogenase/metabolism , Poaceae/enzymology , Amino Acid Sequence , Carboxylic Acids/metabolism , Gene Expression Regulation, Plant , Immunohistochemistry , Malate Dehydrogenase/genetics , Malate Dehydrogenase (NADP+) , Molecular Sequence Data , Plant Leaves/metabolism , Plants, Genetically Modified , Plants, Toxic , Poaceae/genetics , Protein Processing, Post-Translational , RNA, Messenger/metabolism , RNA, Plant/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Starch/metabolism , Nicotiana , Transformation, Genetic
16.
Plant Physiol ; 105(2): 593-600, 1994 Jun.
Article in English | MEDLINE | ID: mdl-12232226

ABSTRACT

Green, mixotrophic tobacco (Nicotiana tabacum) cell cultures in the exponential growth phase were found to have two clearly distinguishable NADP-isocitrate dehydrogenase (ICDH; EC 1.1.1.42) isoenzymes. Their elution behavior during anion-exchange column chromatography was similar to that described previously for the cytosolic (ICDH1) and chloroplastic (ICDH2) enzymes from pea (Pisum sativum) leaves. ICDH2 was absent in etiolated tobacco cell suspensions and appeared during the greening process. Both isoforms were purified to apparent electrophoretic homogeneity by ammonium sulfate fractionation and anion-exchange and affinity chromatography. The isoenzymes were separated on a DEAE-Sephacel column, but the most effective step was a Matrex Red-A column, which enabled an overall purification of 833- and 1328-fold for ICDH1 and ICDH2, respectively. Polyclonal antibodies were raised against each isoform. The ICDH2-specific antibody was used to localize tobacco leaf ICDH2 in situ by an immunogold labeling technique. The enzyme was found largely, if not exclusively, in the chloroplasts of green leaves. ICDH1 and ICDH2 were shown to have apparent native molecular weights of 117,000 and 136,000, respectively, and to consist of identical, 48.5-kD subunits. Similar apparent Km values for NADP, D(+)isocitrate, and Mg2+ were found for the two enzymes when assayed with Mg2+ as the metal cofactor.

17.
Hepatology ; 15(1): 32-6, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1727796

ABSTRACT

The objective was to determine the proportion of patients with chronic hepatitis B in whom hepatitis B virus DNA is demonstrated by polymerase chain reaction after HBeAg to anti-HBe or HBsAg to anti-HBs spontaneous or therapeutically induced seroconversion. Polymerase chain reaction was performed on serum 6 and 12 mo after HBeAg to anti-HBe seroconversion in 12 patients and 2, 6 and 12 mo after HBsAg to anti-HBs seroconversion in 13 patients. Polymerase chain reaction was performed on liver tissue after HBeAg to anti-HBe seroconversion in five patients and after HBsAg to anti-HBs seroconversion in one patient. Serum HBV DNA was demonstrated by polymerase chain reaction in 83% of patients 6 or 12 mo after HBeAg to anti-HBe seroconversion and in 58%, 31% and 15% of patients at 2, 6 and 12 mo, respectively, after HBsAg to anti-HBs seroconversion. Liver HBV DNA was demonstrated by polymerase chain reaction in all patients tested. Our results show that (a) a reduced level of hepatitis B virus replication persists in most of the patients after HBeAg to anti-HBe seroconversion and might be predictive of reactivation, and (b) in contrast, hepatitis B virus replication progressively disappears in most of the patients after HBsAg to anti-HBs seroconversion.


Subject(s)
DNA, Viral/analysis , Hepatitis Antibodies/analysis , Hepatitis B Surface Antigens/immunology , Hepatitis B e Antigens/immunology , Hepatitis B virus/genetics , Hepatitis B/immunology , Liver/metabolism , Polymerase Chain Reaction , Adult , Aged , Chronic Disease , Female , Hepatitis B/genetics , Hepatitis B/therapy , Humans , Male , Middle Aged
19.
Hepatology ; 11(6): 969-74, 1990 Jun.
Article in English | MEDLINE | ID: mdl-2194924

ABSTRACT

We describe four patients with hepatic vein thrombosis caused by Behçet's disease and review the 17 previously published cases. In addition, we compared these 21 cases of hepatic vein thrombosis to our 24 cases of hepatic vein thrombosis caused by primary myeloproliferative disorders. In patients with Behçet's disease, a male predominance (male/female ratio, 19:1) contrasted with the female predominance found in patients with hepatic vein thrombosis complicating primary myeloproliferative disorders (sex ratio = 1:3). The mean age at clinical onset was younger in patients with Behçet's disease than in those with primary myeloproliferative disorders (29 vs. 35 yr). Obstruction of the inferior vena cava was found in 90% of patients with hepatic vein thrombosis caused by Behçet's disease. Inferior vena caval thrombosis appears to be the main pathophysiological mechanism of hepatic vein thrombosis in patients with Behçet's disease. Unlike patients with primary myeloproliferative disorders who often had a progressive course, one third of patients with Behçet's disease had acute liver failure and died within 2 wk of clinical onset. These findings suggest that, in patients with Behçet's disease, hepatic vein thrombosis is a sudden event usually related to the extension of a caval thrombus to the ostium of the hepatic veins.


Subject(s)
Behcet Syndrome/complications , Budd-Chiari Syndrome/etiology , Adolescent , Adult , Aged , Budd-Chiari Syndrome/drug therapy , Budd-Chiari Syndrome/surgery , Female , Humans , Male , Middle Aged , Myeloproliferative Disorders/complications , Survival Analysis
20.
Gastroenterol Clin Biol ; 14(6-7): 596-8, 1990.
Article in French | MEDLINE | ID: mdl-2397870

ABSTRACT

A 24 year-old patient with a short-bowel syndrome receiving home parenteral nutrition in addition to oral feeding for 32 months was treated by oral trimethoprim-sulfamethoxazole for urinary tract infection. Three days later, he developed neurologic disorders associated with severe hyperchloremic acidosis and high plasma level of D-lactate. This is a rare complication of intestinal malabsorption due to small bowel by-pass or extensive resection due to transient alteration of intestinal microflora induced by the oral antibiotic treatment. Diagnosis requires a high indice of suspicion.


Subject(s)
Acidosis, Lactic/complications , Malabsorption Syndromes/complications , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects , Acidosis, Lactic/blood , Adult , Humans , Intestine, Small , Lactates/blood , Male , Nervous System Diseases/etiology , Syndrome , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Urinary Tract Infections/drug therapy
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