Glutaminase is considered as the main glutamate producer enzyme in brain. Consequently, the enzym... more Glutaminase is considered as the main glutamate producer enzyme in brain. Consequently, the enzyme is essential for both glutamatergic and gabaergic transmissions. Glutamine-derived glutamate and ammonia, the products of glutaminase reaction, fulfill crucial roles in energy metabolism and in the biosynthesis of basic metabolites, such as GABA, proteins and glutathione. However, glutamate and ammonia are also hazardous compounds and danger lurks in their generation beyond normal physiological thresholds; hence, glutaminase activity must be carefully regulated in the mammalian brain. The differential distribution and regulation of glutaminase are key factors to modulate the metabolism of glutamate and glutamine in brain. The discovery of novel isoenzymes, protein interacting partners and subcellular localizations indicate new functions for brain glutaminase. In this short review, we summarize recent findings that point consistently towards glutaminase as a multifaceted protein able to perform different tasks. Finally, we will highlight the involvement of glutaminase in pathological states and its consideration as a potential therapeutic target.
International Journal of Biochemistry & Cell Biology, 2002
Glutamine is a multifaceted amino acid used for hepatic urea synthesis, renal ammoniagenesis, glu... more Glutamine is a multifaceted amino acid used for hepatic urea synthesis, renal ammoniagenesis, gluconeogenesis in both liver and kidney, and as a major respiratory fuel for many cells. Decreased glutamine concentrations are found during catabolic stress and are related to susceptibility to infections. Besides, glutamine is not only an important energy source in mitochondria, but is also a precursor of the brain neurotransmitter glutamate, which is likewise used for biosynthesis of the cellular antioxidant glutathione. Reactive oxygen species, such as superoxide anions and hydrogen peroxide, function as intracellular second messengers activating, among others, apoptosis, whereas glutamine is an apoptosis suppressor. In fact, it could contribute to block apoptosis induced by exogenous agents or by intracellular stimuli. In conclusion, this article shows evidences for the important role of glutamine in the regulation of the cellular redox balance, including brain oxidative metabolism, apoptosis and tumour cell proliferation.
The enzyme glutaminase in brain is responsible for the synthesis of neurotransmitter glutamate. W... more The enzyme glutaminase in brain is responsible for the synthesis of neurotransmitter glutamate. We used the two-hybrid genetic selection system in yeast to look for interactors of glutaminase in human brain. We have identified two proteins containing PDZ domains, α1-syntrophin and a glutaminase-interacting protein, named GIP, that showed association with human glutaminase L, as deduced from specificity test of the two-hybrid system. The complete GIP cDNA clone has 1315 nucleotides with a 372-base open reading frame encoding a 124-amino acids protein. Glutaminase associates with both PDZ proteins through its C-terminal end; mutagenesis of single amino acids revealed the sequence -ESXV as essential for the interaction. These data suggest the possibility that PDZ domain-containing proteins are involved in the regulation of glutaminase in brain.
Ferricyanide reductase activity of plasma membranes isolated from Ehrlich ascites tumour cells wa... more Ferricyanide reductase activity of plasma membranes isolated from Ehrlich ascites tumour cells was very sensitive to trypsin treatment. The decreases of activity observed after treatment with different glycosidases suggests that ferricyanide reductase is a glycoprotein. The opposite effects of phospholipase A2 and phospholipase C on the redox activity indicate that the phospholipidic environment plays an important role in the function of ferricyanide reductase. Sodium ions at millimolar concentrations, and some divalent cations at micromolar concentrations (Ca2+, Mg2+, Sr2+, and Mn2+) behaved as stimulators of ferricyanide reductase activity.
Glutaminase (EC 3.5.1.2) is a key enzyme in rapidly proliferating cells. Using anti-sense technol... more Glutaminase (EC 3.5.1.2) is a key enzyme in rapidly proliferating cells. Using anti-sense technology, an Ehrlich ascites tumor cell line (0.28AS-2) with reduced glutaminase activity has been obtained. We investigated the in vivo growth characteristics of the 0.28AS-2 cells. When injected i.p. into normal Swiss albino mice, the 0.28AS-2 cells were unable to grow. On the contrary, when injected into nude mice, they developed into solid tumors. Mice inoculated with 0.28AS-2 cells kept immunologic memory and rejected a second inoculation with parental Ehrlich ascites tumor cells. Expression of both polymorphic epithelial mucin-1 (MUC-1) and the enzyme N-acetyl-␣-D-galactosaminidase, proteins implicated in host immune system escape, were markedly diminished in 0.
Tumor cells suffer a metabolic reprogramming which allows them to use metabolic fuels (glucose, g... more Tumor cells suffer a metabolic reprogramming which allows them to use metabolic fuels (glucose, glutamine, lipids) through anabolic fates to support their enhanced proliferation and other carcinogenesis-related features. The present review tries to address and summarize the broad and growing information available about this reprogramming, whose pieces, put together, make up a complex scheme that encompasses different complexity scales, from cells to systemic networks.
During the growth of a tumor, there are very relevant changes in the metabolism of the host to pr... more During the growth of a tumor, there are very relevant changes in the metabolism of the host to produce the metabolites rapidly consumed by the tumor. In this context, the exchanges of amino acids between the tumor and its host are especially important; however, they have received little attention. A rigorous study must provide data on the growth curve of the tumor, as well as on amino acid levels in tumor cells, plasma, and metabolically relevant tissues and organs from the host during the whole growth of the tumor. The main conclusions arising from a complete study in a tumor model are discussed.
The protein glutaminase has been traditionally considered as a mitochondrial enzyme, playing a ke... more The protein glutaminase has been traditionally considered as a mitochondrial enzyme, playing a key role in the energy and nitrogen metabolism of mammalian cells. However, new experimental evidence in the last few years has challenged this simplified view. The recent discovery of novel extramitochondrial localizations, the identification of potential protein interacting partners, the existence of multiple transcripts for mammalian glutaminase genes, and the presence of signature sequences and protein motifs on its sequence support the notion of glutaminase being a multifaceted protein, which may be involved in other functions besides glutamate generation from glutamine. In this short review, we will briefly summarize recent works on glutaminase proteins in mammals, with particular emphasis in brain studies. This experimental evidence will then be used to highlight new potential roles for this classical metabolic enzyme.
Glutamine is an essential amino acid in cancer cells and is required for the growth of many other... more Glutamine is an essential amino acid in cancer cells and is required for the growth of many other cell types. Glutaminase activity is positively correlated with malignancy in tumours and with growth rate in normal cells. In the present work, Ehrlich ascites tumour cells, and their derivative, 0.28AS-2 cells, expressing antisense glutaminase mRNA, were assayed for apoptosis induced by methotrexate and hydrogen peroxide. It is shown that Ehrlich ascites tumour cells, expressing antisense mRNA for glutaminase, contain lower levels of glutathione than normal ascites cells. In addition, 0.28AS-2 cells contain a higher number of apoptotic cells and are more sensitive to both methotrexate and hydrogen peroxide toxicity than normal cells. Taken together, these results provide insights into the role of glutaminase in apoptosis by demonstrating that the expression of antisense mRNA for glutaminase alters apoptosis and glutathione antioxidant capacity.
Tumours must avoid host immune response to survive and proliferate; to achieve this purpose, tumo... more Tumours must avoid host immune response to survive and proliferate; to achieve this purpose, tumours interact with cells of the immune system by means of tumour secreted factors. The alterations of splenic cell populations in mice bearing the Ehrlich ascites tumour have been studied. A rapid and acute response was observed, characterized by a decrease in both CD4 and CD8 T cells, and a transient increase in the number of B cells, which peaked 2 days after tumour inoculation. An increase in macrophage population and in the homing antigen CD18 was also detected. In vitro incubations of splenic cells with the Staphylococcus aureus enterotoxin B (SEB) showed that tumour induces a state of reduced responsiveness to stimulation of T cells, mainly affecting CD8 T cells, and a diminished IFN-g expression.
Biochimica Et Biophysica Acta-molecular Cell Research, 1996
Diacyl glycerols and phorbol esters, which activate protein kinases C, stimulated Ehrlich ascites... more Diacyl glycerols and phorbol esters, which activate protein kinases C, stimulated Ehrlich ascites tumor cell ferricyanide reductase activity. On the contrary, selective inhibition of active protein kinases C with bis-indolyl maleimide did not change the rate of ferricyanide reduction by Ehrlich cells. Selective inhibitors of phosphoprotein phosphatases, okadaic acid and cyclosporin A, also stimulated plasma membrane redox system. Taking all these data together, protein kinases or phosphoprotein phosphatases seemed to be involved in the multiple and complex regulation of Ehrlich cell plasma membrane redox system.
Ehrlich cell plasma membrane ferricyanide reductase activity increased in the presence of mastopa... more Ehrlich cell plasma membrane ferricyanide reductase activity increased in the presence of mastoparan, a generic activator of G proteins, using either whole cells or isolated plasma membrane fractions. Agents that increase intracellularcAMP also increased the rate of ferricyanide reduction by Ehrlich cells. For the first time, evidence is shown on a modulation of plasma membrane redox system bycGMP. In fact, permeant analogs ofcGMP, dibutyrylcGMP, and 8-bromo-cGMP increased the rate of ferricyanide reduction by the Ehrlich cell plasma membrane redox system. Furthermore, specific inhibition ofcGMP-phosphodiesterases by dipyridamole was also accompanied by an enhancement in the rate of ferricyanide reduction. On the other hand, treatments expected to increase cytoplasmic Ca2+ concentrations were accompanied by a remarkable stimulation of the reductase activity. Taking all these data together, it seems that the Ehrlich cell plasma membrane redox system is under a multiple and complex regulation by different signal transduction pathways involving G proteins, cyclic nucleotides, and Ca2+ ions.
Tumors are characterized by their ability to avoid the host immune system. Ehrlich ascites tumor ... more Tumors are characterized by their ability to avoid the host immune system. Ehrlich ascites tumor cells were used to investigate the early alterations of the host immune system after tumor inoculation. The results show that frequencies of splenic Th lymphocytes were drastically reduced during tumor growth, reaching a minimum only two days after tumor inoculation. The frequency of splenic CD4+ lymphocytes expressing IFN-γ was significantly increased, although the total number was unchanged, suggesting that there was no net induction of Th1-type response. Splenic macrophages were increased, in both frequency and cell number, after four days of tumor growth. The same pattern was observed when mice were inoculated with cell free ascitic fluid. TGF-β precursors were detected in tumor cells as well as in ascitic fluid. The data suggest that tumor actively interacts with host immune system by means of tumor cell secreted factors.
To review the course, predisposing risk factors, treatment employed, and complications of autoimm... more To review the course, predisposing risk factors, treatment employed, and complications of autoimmune hepatitis (AIH) during pregnancy. Maternal and fetal outcomes will be discussed. We reviewed the literature from February 1966 to January 2004 using MEDLINE and the key words autoimmune hepatitis, chronic active hepatitis, lupoid hepatitis, and pregnancy. An additional case of ours was included as she had AIH since childhood with worsening of liver disease during pregnancy. Including the present case, 58 pregnant women with AIH were reported in 17 case reports and series. In the 101 pregnancies documented in these cases, there were 47 flare-ups, 5 clinical improvements, 45 stabilizations of the disease during pregnancy, and 4 cases in which the disease course was not reported. Two maternal deaths occurred. A perinatal mortality of 4% and 19 fetal deaths were described. Most women were treated with prednisone alone; however azathioprine was used in a number of patients. Pregnancy course in patients with AIH is unpredictable. AIH exacerbates in some patients and is associated with a high rate of fetal complications including prematurity and death. Low-dose prednisone seems to be the preferred treatment. The use of azathioprine must be individualized and further studies are needed to better define its role and safety during pregnancy in patients with AIH. A better understanding of the course of pregnancy in patients with AIH should help design appropriate therapeutic schemes to improve pregnancy outcomes for both mother and fetus.
The idiopathic inflammatory myopathies embody the largest group of acquired and potentially treat... more The idiopathic inflammatory myopathies embody the largest group of acquired and potentially treatable causes of skeletal muscle weakness. The three major groups of this disorder are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. Corticosteroids continue to be the mainstay of initial treatment in the majority of cases of PM/DM. The treatment of refractory disease can be challenging despite the utilization of the medications currently available. We report two patients with refractory DM who were treated with infliximab. We describe their presentation, clinical course, treatment, and outcomes.
Kawasaki disease (KD) is a systemic vasculitis that predominantly affects infants and young child... more Kawasaki disease (KD) is a systemic vasculitis that predominantly affects infants and young children. Asian race has been described as an important factor for the development of this disease. We reported our experience in a cohort of patients with KD. Clinical and laboratory data from initial presentation and follow-up visits were reviewed in 88 patients with KD treated at Children's Hospital of New Orleans between March 1993 and November 2004. Forty-nine (56%) patients were African American, 35 (40%) Caucasian, two (3%) Asian and two (3%) Hispanic. Coronary artery aneurysms (CAAs) were detected in 15 (17%) patients. CAAs were less frequent in African-American patients compared to Caucasians [relative risk (RR)=0.2, 95% CI: 0.04400-0.8405, p=0.0164]. Eighty-three patients responded to one dose of intravenous human immunoglobulin (IVIG), five patients responded to a second infusion of IVIG, and two who were IVIG resistant responded only following methylprednisolone pulse. Hemoglobin (Hb) levels of <10 g/dl and presence of polymorphic rash were significantly correlated with development of CAAs. No deaths were observed.
Reactive arthritis (ReA) is characterized by an aseptic inflammatory articular involvement occurr... more Reactive arthritis (ReA) is characterized by an aseptic inflammatory articular involvement occurring in a genetically predisposed individual secondary to an infectious process localized outside the joint. ReA usually refers to an acute or insidious oligoarthritis process after enteric (enteroarthritis) or urogenital (uroarthritis) infection. Conventional antirheumatic therapeutic modalities based on nonsteroid anti-inflammatory drugs, sulfasalazine, and steroids are effective in the majority of patients. In more refractory cases, the use of second-line agents including methotrexate and more recently biological agents such as etanercept and infliximab has been found highly effective. The role of antibiotics remains not well established, although they appear to be effective in acute ReA of urogenital origin.
Glutaminase is considered as the main glutamate producer enzyme in brain. Consequently, the enzym... more Glutaminase is considered as the main glutamate producer enzyme in brain. Consequently, the enzyme is essential for both glutamatergic and gabaergic transmissions. Glutamine-derived glutamate and ammonia, the products of glutaminase reaction, fulfill crucial roles in energy metabolism and in the biosynthesis of basic metabolites, such as GABA, proteins and glutathione. However, glutamate and ammonia are also hazardous compounds and danger lurks in their generation beyond normal physiological thresholds; hence, glutaminase activity must be carefully regulated in the mammalian brain. The differential distribution and regulation of glutaminase are key factors to modulate the metabolism of glutamate and glutamine in brain. The discovery of novel isoenzymes, protein interacting partners and subcellular localizations indicate new functions for brain glutaminase. In this short review, we summarize recent findings that point consistently towards glutaminase as a multifaceted protein able to perform different tasks. Finally, we will highlight the involvement of glutaminase in pathological states and its consideration as a potential therapeutic target.
International Journal of Biochemistry & Cell Biology, 2002
Glutamine is a multifaceted amino acid used for hepatic urea synthesis, renal ammoniagenesis, glu... more Glutamine is a multifaceted amino acid used for hepatic urea synthesis, renal ammoniagenesis, gluconeogenesis in both liver and kidney, and as a major respiratory fuel for many cells. Decreased glutamine concentrations are found during catabolic stress and are related to susceptibility to infections. Besides, glutamine is not only an important energy source in mitochondria, but is also a precursor of the brain neurotransmitter glutamate, which is likewise used for biosynthesis of the cellular antioxidant glutathione. Reactive oxygen species, such as superoxide anions and hydrogen peroxide, function as intracellular second messengers activating, among others, apoptosis, whereas glutamine is an apoptosis suppressor. In fact, it could contribute to block apoptosis induced by exogenous agents or by intracellular stimuli. In conclusion, this article shows evidences for the important role of glutamine in the regulation of the cellular redox balance, including brain oxidative metabolism, apoptosis and tumour cell proliferation.
The enzyme glutaminase in brain is responsible for the synthesis of neurotransmitter glutamate. W... more The enzyme glutaminase in brain is responsible for the synthesis of neurotransmitter glutamate. We used the two-hybrid genetic selection system in yeast to look for interactors of glutaminase in human brain. We have identified two proteins containing PDZ domains, α1-syntrophin and a glutaminase-interacting protein, named GIP, that showed association with human glutaminase L, as deduced from specificity test of the two-hybrid system. The complete GIP cDNA clone has 1315 nucleotides with a 372-base open reading frame encoding a 124-amino acids protein. Glutaminase associates with both PDZ proteins through its C-terminal end; mutagenesis of single amino acids revealed the sequence -ESXV as essential for the interaction. These data suggest the possibility that PDZ domain-containing proteins are involved in the regulation of glutaminase in brain.
Ferricyanide reductase activity of plasma membranes isolated from Ehrlich ascites tumour cells wa... more Ferricyanide reductase activity of plasma membranes isolated from Ehrlich ascites tumour cells was very sensitive to trypsin treatment. The decreases of activity observed after treatment with different glycosidases suggests that ferricyanide reductase is a glycoprotein. The opposite effects of phospholipase A2 and phospholipase C on the redox activity indicate that the phospholipidic environment plays an important role in the function of ferricyanide reductase. Sodium ions at millimolar concentrations, and some divalent cations at micromolar concentrations (Ca2+, Mg2+, Sr2+, and Mn2+) behaved as stimulators of ferricyanide reductase activity.
Glutaminase (EC 3.5.1.2) is a key enzyme in rapidly proliferating cells. Using anti-sense technol... more Glutaminase (EC 3.5.1.2) is a key enzyme in rapidly proliferating cells. Using anti-sense technology, an Ehrlich ascites tumor cell line (0.28AS-2) with reduced glutaminase activity has been obtained. We investigated the in vivo growth characteristics of the 0.28AS-2 cells. When injected i.p. into normal Swiss albino mice, the 0.28AS-2 cells were unable to grow. On the contrary, when injected into nude mice, they developed into solid tumors. Mice inoculated with 0.28AS-2 cells kept immunologic memory and rejected a second inoculation with parental Ehrlich ascites tumor cells. Expression of both polymorphic epithelial mucin-1 (MUC-1) and the enzyme N-acetyl-␣-D-galactosaminidase, proteins implicated in host immune system escape, were markedly diminished in 0.
Tumor cells suffer a metabolic reprogramming which allows them to use metabolic fuels (glucose, g... more Tumor cells suffer a metabolic reprogramming which allows them to use metabolic fuels (glucose, glutamine, lipids) through anabolic fates to support their enhanced proliferation and other carcinogenesis-related features. The present review tries to address and summarize the broad and growing information available about this reprogramming, whose pieces, put together, make up a complex scheme that encompasses different complexity scales, from cells to systemic networks.
During the growth of a tumor, there are very relevant changes in the metabolism of the host to pr... more During the growth of a tumor, there are very relevant changes in the metabolism of the host to produce the metabolites rapidly consumed by the tumor. In this context, the exchanges of amino acids between the tumor and its host are especially important; however, they have received little attention. A rigorous study must provide data on the growth curve of the tumor, as well as on amino acid levels in tumor cells, plasma, and metabolically relevant tissues and organs from the host during the whole growth of the tumor. The main conclusions arising from a complete study in a tumor model are discussed.
The protein glutaminase has been traditionally considered as a mitochondrial enzyme, playing a ke... more The protein glutaminase has been traditionally considered as a mitochondrial enzyme, playing a key role in the energy and nitrogen metabolism of mammalian cells. However, new experimental evidence in the last few years has challenged this simplified view. The recent discovery of novel extramitochondrial localizations, the identification of potential protein interacting partners, the existence of multiple transcripts for mammalian glutaminase genes, and the presence of signature sequences and protein motifs on its sequence support the notion of glutaminase being a multifaceted protein, which may be involved in other functions besides glutamate generation from glutamine. In this short review, we will briefly summarize recent works on glutaminase proteins in mammals, with particular emphasis in brain studies. This experimental evidence will then be used to highlight new potential roles for this classical metabolic enzyme.
Glutamine is an essential amino acid in cancer cells and is required for the growth of many other... more Glutamine is an essential amino acid in cancer cells and is required for the growth of many other cell types. Glutaminase activity is positively correlated with malignancy in tumours and with growth rate in normal cells. In the present work, Ehrlich ascites tumour cells, and their derivative, 0.28AS-2 cells, expressing antisense glutaminase mRNA, were assayed for apoptosis induced by methotrexate and hydrogen peroxide. It is shown that Ehrlich ascites tumour cells, expressing antisense mRNA for glutaminase, contain lower levels of glutathione than normal ascites cells. In addition, 0.28AS-2 cells contain a higher number of apoptotic cells and are more sensitive to both methotrexate and hydrogen peroxide toxicity than normal cells. Taken together, these results provide insights into the role of glutaminase in apoptosis by demonstrating that the expression of antisense mRNA for glutaminase alters apoptosis and glutathione antioxidant capacity.
Tumours must avoid host immune response to survive and proliferate; to achieve this purpose, tumo... more Tumours must avoid host immune response to survive and proliferate; to achieve this purpose, tumours interact with cells of the immune system by means of tumour secreted factors. The alterations of splenic cell populations in mice bearing the Ehrlich ascites tumour have been studied. A rapid and acute response was observed, characterized by a decrease in both CD4 and CD8 T cells, and a transient increase in the number of B cells, which peaked 2 days after tumour inoculation. An increase in macrophage population and in the homing antigen CD18 was also detected. In vitro incubations of splenic cells with the Staphylococcus aureus enterotoxin B (SEB) showed that tumour induces a state of reduced responsiveness to stimulation of T cells, mainly affecting CD8 T cells, and a diminished IFN-g expression.
Biochimica Et Biophysica Acta-molecular Cell Research, 1996
Diacyl glycerols and phorbol esters, which activate protein kinases C, stimulated Ehrlich ascites... more Diacyl glycerols and phorbol esters, which activate protein kinases C, stimulated Ehrlich ascites tumor cell ferricyanide reductase activity. On the contrary, selective inhibition of active protein kinases C with bis-indolyl maleimide did not change the rate of ferricyanide reduction by Ehrlich cells. Selective inhibitors of phosphoprotein phosphatases, okadaic acid and cyclosporin A, also stimulated plasma membrane redox system. Taking all these data together, protein kinases or phosphoprotein phosphatases seemed to be involved in the multiple and complex regulation of Ehrlich cell plasma membrane redox system.
Ehrlich cell plasma membrane ferricyanide reductase activity increased in the presence of mastopa... more Ehrlich cell plasma membrane ferricyanide reductase activity increased in the presence of mastoparan, a generic activator of G proteins, using either whole cells or isolated plasma membrane fractions. Agents that increase intracellularcAMP also increased the rate of ferricyanide reduction by Ehrlich cells. For the first time, evidence is shown on a modulation of plasma membrane redox system bycGMP. In fact, permeant analogs ofcGMP, dibutyrylcGMP, and 8-bromo-cGMP increased the rate of ferricyanide reduction by the Ehrlich cell plasma membrane redox system. Furthermore, specific inhibition ofcGMP-phosphodiesterases by dipyridamole was also accompanied by an enhancement in the rate of ferricyanide reduction. On the other hand, treatments expected to increase cytoplasmic Ca2+ concentrations were accompanied by a remarkable stimulation of the reductase activity. Taking all these data together, it seems that the Ehrlich cell plasma membrane redox system is under a multiple and complex regulation by different signal transduction pathways involving G proteins, cyclic nucleotides, and Ca2+ ions.
Tumors are characterized by their ability to avoid the host immune system. Ehrlich ascites tumor ... more Tumors are characterized by their ability to avoid the host immune system. Ehrlich ascites tumor cells were used to investigate the early alterations of the host immune system after tumor inoculation. The results show that frequencies of splenic Th lymphocytes were drastically reduced during tumor growth, reaching a minimum only two days after tumor inoculation. The frequency of splenic CD4+ lymphocytes expressing IFN-γ was significantly increased, although the total number was unchanged, suggesting that there was no net induction of Th1-type response. Splenic macrophages were increased, in both frequency and cell number, after four days of tumor growth. The same pattern was observed when mice were inoculated with cell free ascitic fluid. TGF-β precursors were detected in tumor cells as well as in ascitic fluid. The data suggest that tumor actively interacts with host immune system by means of tumor cell secreted factors.
To review the course, predisposing risk factors, treatment employed, and complications of autoimm... more To review the course, predisposing risk factors, treatment employed, and complications of autoimmune hepatitis (AIH) during pregnancy. Maternal and fetal outcomes will be discussed. We reviewed the literature from February 1966 to January 2004 using MEDLINE and the key words autoimmune hepatitis, chronic active hepatitis, lupoid hepatitis, and pregnancy. An additional case of ours was included as she had AIH since childhood with worsening of liver disease during pregnancy. Including the present case, 58 pregnant women with AIH were reported in 17 case reports and series. In the 101 pregnancies documented in these cases, there were 47 flare-ups, 5 clinical improvements, 45 stabilizations of the disease during pregnancy, and 4 cases in which the disease course was not reported. Two maternal deaths occurred. A perinatal mortality of 4% and 19 fetal deaths were described. Most women were treated with prednisone alone; however azathioprine was used in a number of patients. Pregnancy course in patients with AIH is unpredictable. AIH exacerbates in some patients and is associated with a high rate of fetal complications including prematurity and death. Low-dose prednisone seems to be the preferred treatment. The use of azathioprine must be individualized and further studies are needed to better define its role and safety during pregnancy in patients with AIH. A better understanding of the course of pregnancy in patients with AIH should help design appropriate therapeutic schemes to improve pregnancy outcomes for both mother and fetus.
The idiopathic inflammatory myopathies embody the largest group of acquired and potentially treat... more The idiopathic inflammatory myopathies embody the largest group of acquired and potentially treatable causes of skeletal muscle weakness. The three major groups of this disorder are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. Corticosteroids continue to be the mainstay of initial treatment in the majority of cases of PM/DM. The treatment of refractory disease can be challenging despite the utilization of the medications currently available. We report two patients with refractory DM who were treated with infliximab. We describe their presentation, clinical course, treatment, and outcomes.
Kawasaki disease (KD) is a systemic vasculitis that predominantly affects infants and young child... more Kawasaki disease (KD) is a systemic vasculitis that predominantly affects infants and young children. Asian race has been described as an important factor for the development of this disease. We reported our experience in a cohort of patients with KD. Clinical and laboratory data from initial presentation and follow-up visits were reviewed in 88 patients with KD treated at Children's Hospital of New Orleans between March 1993 and November 2004. Forty-nine (56%) patients were African American, 35 (40%) Caucasian, two (3%) Asian and two (3%) Hispanic. Coronary artery aneurysms (CAAs) were detected in 15 (17%) patients. CAAs were less frequent in African-American patients compared to Caucasians [relative risk (RR)=0.2, 95% CI: 0.04400-0.8405, p=0.0164]. Eighty-three patients responded to one dose of intravenous human immunoglobulin (IVIG), five patients responded to a second infusion of IVIG, and two who were IVIG resistant responded only following methylprednisolone pulse. Hemoglobin (Hb) levels of <10 g/dl and presence of polymorphic rash were significantly correlated with development of CAAs. No deaths were observed.
Reactive arthritis (ReA) is characterized by an aseptic inflammatory articular involvement occurr... more Reactive arthritis (ReA) is characterized by an aseptic inflammatory articular involvement occurring in a genetically predisposed individual secondary to an infectious process localized outside the joint. ReA usually refers to an acute or insidious oligoarthritis process after enteric (enteroarthritis) or urogenital (uroarthritis) infection. Conventional antirheumatic therapeutic modalities based on nonsteroid anti-inflammatory drugs, sulfasalazine, and steroids are effective in the majority of patients. In more refractory cases, the use of second-line agents including methotrexate and more recently biological agents such as etanercept and infliximab has been found highly effective. The role of antibiotics remains not well established, although they appear to be effective in acute ReA of urogenital origin.
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Papers by Javier Marquez