Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 affected individuals. We identified recessive mutations in EPG5 (previously KIAA1632), indicating a causative role in Vici syndrome. EPG5 is the human homolog of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomes. Further studies showed a severe block in autophagosomal clearance in muscle and fibroblasts from individuals with mutant EPG5, resulting in the accumulation of autophagic cargo in autophagosomes. These findings position Vici syndrome as a paradigm of human multisystem disorders associated with defective autophagy and suggest a fundamental role of the autophagy pathway in the immune system and the anatomical and functional formation of organs such as the brain and heart.
 ...
PMID:Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy. 2322 57

Sepsis in patients with human immunodeficiency virus (HIV) may be associated with the appearance of cardiac dysfunction. This is a challenge, both when making the differential diagnosis and determining the proper treatment, as there are numerous risk factors: Myocarditis due to the HIV itself, the presence or absence of highly active antiretroviral therapy, toxic substances, and cardiomyopathy associated with sepsis. The diagnostic and therapeutic approach to an HIV positive patient with septic shock and cardiac dysfunction is described, as well as a brief review of the different causes of cardiomyopathy which may affect this group of patients is also presented.
...
PMID:[Sepsis, cardiomyopathy and human immunodeficiency virus infection: presentation of a case]. 2370 36

The association between Castleman's disease (CD) and cardiomyopathy has been rarely reported and the optimal therapeutic approach remains unknown. We report a previously healthy 20-year-old African American female who presented with fever, dyspnea, anasarca, and generalized lymphadenopathy. Diagnostic workup, including an axillary lymph node biopsy, revealed that she had human immunodeficiency virus-negative and human herpes virus-8-negative multicentric CD. She had a non-anaphylactoid infusion reaction during her fourth rituximab infusion. A few weeks later, she developed new-onset severe cardiomyopathy requiring inotropic therapy, warranting consideration for left ventricular assist device. Several clinical clues indicated her new-onset heart failure was a manifestation of her CD. Interestingly, a trial of tocilizumab (an anti-interleukin-6 receptor monoclonal antibody) resulted in complete resolution of her cardiomyopathy and other manifestations of CD. Tocilizumab received orphan drug approval for the treatment of CD in Japan, but is not yet approved for this indication in the United States. Clinicians should be aware of its potential clinical utility in CD.
...
PMID:Reversal of cardiomyopathy with tocilizumab in a case of HIV-negative Castleman's disease. 2378 62

From a global perspective, cardiovascular disease (CVD) in human immunodeficiency virus (HIV) may result from cardiac involvement upon presentation of opportunistic infections in the presence of advanced immunosuppression, be a consequence of HIV-induced immune activation or derive from antiretroviral therapy-associated dyslipidaemia and insulin resistance. Indeed, in developed countries with unlimited access to antiretroviral therapy CVD has become one of the major causes of death in HIV. Therefore, cardiovascular risk reduction and lifestyle modifications are essential and careful selection of the antiretroviral drugs according to underlying cardiovascular risk factors of great importance. In developing countries with delayed roll-out of antiretroviral therapy pericardial disease (often related to TB), HIV-associated cardiomyopathy, and HIV-associated pulmonary hypertension are the most common cardiac manifestations in HIV. In Africa, the epicentre of the HIV epidemic, dynamic socio-economic and lifestyle factors characteristic of epidemiological transition appear to have positioned the urban African community at the cross-roads between historically prevalent and 'new' forms of CVD, such as coronary artery disease. In this context, cardiovascular risk assessment of HIV-infected patients will become a critical element of care in developing countries similar to the developed world, and access to antiretroviral therapy with little or no impact on lipid and glucose metabolism of importance to reduce CVD in HIV.
...
PMID:HIV and the heart: the impact of antiretroviral therapy: a global perspective. 2412 82

Epidemiological studies suggest that retroviruses, including human immunodeficiency virus type 1, are associated with cardiomyopathy and myocarditis, but a causal relationship remains to be established. We encountered unusual cardiomyocyte hypertrophy and mitosis in Japanese native fowls infected with subgroup A of the avian leukosis viruses (ALVs-A), which belong to the genus Alpharetrovirus of the family Retroviridae and mainly induce lymphoid neoplasm in chickens. The affected hearts were evaluated by histopathology and immunohistochemistry, viral isolation, viral genome sequencing and experimental infection. There was non-suppurative myocarditis in eighteen fowls and seven of them had abnormal cardiomyocytes, which were distributed predominantly in the left ventricular wall and showed hypertrophic cytoplasm and atypical large nuclei. Nuclear chains and mitosis were frequently noted in these cardiomyocytes and immunohistochemistry for proliferating cell nuclear antigen supported the enhancement of mitotic activity. ALVs were isolated from all affected cases and phylogenic analysis of envSU genes showed that the isolates were mainly classified into two different clusters, suggesting viral genome diversity. In ovo experimental infection with two of the isolates was demonstrated to cause myocarditis and cardiomyocyte hypertrophy similar to those in the naturally occurring lesions and cardiac hamartoma (rhabdomyoma) in a shorter period of time (at 70 days of age) than expected. These results indicate that ALVs cause myocarditis as well as cardiomyocyte abnormality in chickens, implying a pathogenetic mechanism different from insertional mutagenesis and the existence of retrovirus-induced heart disorder.
...
PMID:Cardiac pathology and molecular epidemiology by avian leukosis viruses in Japan. 2446 46

In 2012, the United Nations estimated that globally, 34 million people were living with human immunodeficiency virus (HIV) infection at the end of 2011. About 6.5% of AIDS-related mortality is attributable to cardiovascular disease. HIV related cardiovascular disease is diverse. In this review we explore the different disease states associated with HIV such as cardiomyopathy, coronary artery disease, dyslipidemia, electrocardiographic abnormalities, prolonged QT interval and sudden death. The pathophysiology of these numerous diseases is complex and multifactorial. Current management of these patients is challenging due to multiple drug-drug interactions and side effects. However, the approach to prevention is quite familiar, taking on the same rules that apply for any patient to minimize cardiovascular disease risk. The challenges are many, therefore for HIV patients who present after a cardiovascular event, or for prevention of cardiovascular disease, the concept of a heart team is essential, where cardiovascular specialists and the HIV care team work side by side to ensure safety of medications (avoid drug interactions) and to institute a goal directed prevention plan of care.
 ...
PMID:Cardiovascular disease in patients with chronic human immunodeficiency virus infection. 2479 79

Vici syndrome is a rare autosomal recessively inherited multisystem disorder characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, psychomotor delay, and hypopigmentation. Cullup et al. recently identified mutations in the gene EPG5 as the cause of Vici syndrome. EPG5 is involved in autophagy, an evolutionarily conserved lysosomal degradation process that is essential for cell homeostasis. Following the first description in 1988 by Vici et al., 24 other cases of Vici syndrome have been published with variable expression of the defining features. Here, we report on a further case of Vici syndrome with a homozygous truncating mutation of EPG5, identified by whole-exome sequencing. The mutation in our patient is the first reported affecting the penultimate exon of EPG5 and presenting with typical clinical manifestations of Vici syndrome. Additionally, we present a detailed clinical analysis of Vici syndrome comprising all cases previously described in the literature.
 ...
PMID:First description of a patient with Vici syndrome due to a mutation affecting the penultimate exon of EPG5 and review of the literature. 2533 54

Acquired immune deficiency syndrome (AIDS) is responsible for significant morbidity and mortality in the United States and other countries. Cardiac involvement in AIDS, which was previously felt to be an unusual manifestation of the disease, is now being described with increasing frequency. Clinical and necropsy studies have demonstrated myocarditis, myocardial necrosis, cardiomyopathy, pericardial disease, endocarditis, pulmonary hypertension, and tumor infiltration in patients dying with AIDS. A direct role for human immunodeficiency virus (HIV-1) in the development of myocarditis, myocardopathy, and pericardial disease has not yet been elucidated. Recent immunopathological evidence suggests a possible role for immune-mediated myocardial inflammatory changes. The drugs used to treat HIV-1 have not been shown to be cardiotoxic; however, there are suggestions that azidothymidine (AZT) can cause mitochondrial changes in myocardial muscle. There are also suggestions that the cardiac complications of AIDS are different in patients whose risk factor for HIV infection is homosexual practice compared with patients having intravenous drug addiction as their major risk factor for HIV disease. Risk factors for myocardial disease, other than HIV, may also be contributors to cardiac complications in patients with AIDS who are intravenous drug abusers.
...
PMID:AIDS and the heart: Clinicopathologic assessment. 2585 Oct 5

We studied two monozygotic twins, born to first cousins, affected by a multisystem disease. At birth, they both presented with bilateral cryptorchidism and malformations. Since early adulthood, they developed a slowly progressive neurological syndrome, with cerebellar and pyramidal signs, cognitive impairment, and depression. Dilating cardiomyopathy is also present in both. By whole-exome sequencing, we found a homozygous nucleotide change in XRCC4 (c.673C>T), predicted to introduce a premature stop codon (p.R225*). XRCC4 transcript levels were profoundly reduced, and the protein was undetectable in patients' skin fibroblasts. XRCC4 plays an important role in non-homologous end joining of DNA double-strand breaks (DSB), a system that is involved in repairing DNA damage from, for example, ionizing radiations. Gamma-irradiated mutant cells demonstrated reduction, but not abolition, of DSB repair. In contrast with embryonic lethality of the Xrcc4 KO mouse, nonsense mutations in human XRCC4 have recently been associated with primordial dwarfism and, in our cases, with adult-onset neurological impairment, suggesting an important role for DNA repair in the brain. Surprisingly, neither immunodeficiency nor predisposition to malignancy was reported in these patients.
...
PMID:A nonsense mutation of human XRCC4 is associated with adult-onset progressive encephalocardiomyopathy. 2587 42

Multisystem deterioration occurs mainly in older individuals and may be related to physiological tissue degeneration. However, genetic predisposition may be unmasked by inappropriate functional and structural system deficiencies. McLeod syndrome (MLS) is a rare, multisystem disease which is X-chromosomal inherited and belongs to the neuroacanthocytosis syndromes (NAS). The main clinical manifestations contain progressive neuro-psychiatric and cognitive deterioration, choreatic movement disorder, as well as myopathy, sensory motor axonal neuropathy and cardiomyopathy. In addition, MLS patients have red blood cell abnormalities including immune-hematological, morphological and functional impairments of red blood cells. In large deletions, contiguous gene syndrome may arise, including Duchenne muscular dystrophia, cellular immunodeficiency or retinitis pigmentosa. Hematological abnormalities such as blood group abnormalities in Kell- and XK blood group system, formation of anti-public red blood cell alloantibodies, acanthocytosis and elevated creatinine phosphokinase may precede clinical disease manifestation for decades and provide tools for early diagnosis. Patients with unexplained neuro-muscular deterioration and/or neuro-psychological pathologies accompanied with hematological abnormalities should be investigated for MLS.
...
PMID:Neurodegeneration in the elderly - When the blood type matters: An overview of the McLeod syndrome with focus on hematological features. 2593 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>