Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neonatal abnormalities, treatments and outcomes in a group of 13 cloned transgenic calves and fetuses that progressed into the third trimester of pregnancy are described. From these 13 fetuses, 8 calves were born live, 4 stillborn fetuses were recovered from 3 cows that died 7 d to 2 mo before term, and 1 aborted fetus was recovered at 8 mo gestation. All fetuses and calves were derived from the same male fetal Holstein fibroblast cell line transfected with a beta-galactosidase marker gene. Six calves were delivered by Cesarian section and two by vaginal delivery between 278 and 288 d of gestation. Birth weights ranged from 44 to 58.6 kg. Five of the 8 live born calves were judged to be normal within 4 h of birth based on clinical signs and blood gas measurements. One of these 5 calves died at 6 wk of age from a suspected dilated cardiomyopathy. Three of the 8 calves were diagnosed with neonatal respiratory distress immediately following birth, one of which died (at 4 d of age) as a result of pulmonary surfactant deficiency coupled with pulmonary hypertension and elevated systemic venous pressures. Similar findings of chronic pulmonary hypertension were also observed in 2 of 5 fetuses. Placental edema was present in both calves that later died and in the 2 fetuses with cardiopulmonary abnormalities. Hydrallantois occurred with or without placental edema in 6 cows, and only 1 calf from this group survived. The 6 cows without hydrallantois or placental edema produced 5 live calves and 1 aborted fetus. The cardiopulmonary abnormalities observed in the calves and fetuses occurred in utero in conjunction with placental abnormalities, and it is likely that the cloning technique and/or in vitro embryo culture conditions contributed to these abnormalities, although the mechanism remains to be determined.
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PMID:Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies). 1072 73

Arterial inflammatory responses are thought to be a significant component of atherosclerotic disease. We describe here, using a transgenic approach, the mutual perpetuation of immune-mediated arterial inflammation and cholesterol-induced atherosclerosis. Mice expressing the bacterial transgene beta-galactosidase exclusively in cardiomyocytes and in smooth muscle cells in lung arteries and the aorta (SM-LacZ), and hypercholesterolemic apolipoprotein E-deficient SM-LacZ mice (SM-LacZ/apoE(-/-)) developed myocarditis and arteritis after immunization with dendritic cells presenting a beta-galactosidase-derived immunogenic peptide. Hypercholesterolemia amplified acute arteritis and perpetuated chronic arterial inflammation in SM-LacZ/apoE(-/-) mice, but had no major impact on acute myocarditis or the subsequent development of dilated cardiomyopathy. Conversely, arteritis significantly accelerated cholesterol-induced atherosclerosis. Taken together, these data demonstrate that the linkage of immune-mediated arteritis and hypercholesterolemia favors initiation and maintenance of atherosclerotic lesion formation. Therapeutic strategies to prevent or disrupt such self-perpetuating vicious circles may be crucial for the successful treatment of atherosclerosis.
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PMID:Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model. 1105 Jan 73

ZMPSTE24 encodes the only metalloprotease, which transforms prelamin into mature lamin A. Up to now, mutations in ZMPSTE24 have been linked to Restrictive Dermopathy (RD), Progeria or Mandibulo-Acral Dysplasia (MAD). We report here the phenotype of a patient referred for severe metabolic syndrome and cardiomyopathy, carrying a mutation in ZMPSTE24. The patient presented with a partial lipodystrophic syndrome associating hypertriglyceridemia, early onset type 2 diabetes, and android obesity with truncal and abdominal fat accumulation but without subcutaneous lipoatrophy. Other clinical features included acanthosis nigricans, liver steatosis, dilated cardiomyopathy, and high myocardial and hepatic triglycerides content. Mutated fibroblasts from the patient showed increased nuclear shape abnormalities and premature senescence as demonstrated by a decreased Population Doubling Level, an increased beta-galactosidase activity and a decreased BrdU incorporation rate. Reduced prelamin A expression by siRNA targeted toward LMNA transcripts resulted in decreased nuclear anomalies. We show here that a central obesity without subcutaneous lipoatrophy is associated with a laminopathy due to a heterozygous missense mutation in ZMPSTE24. Given the high prevalence of metabolic syndrome and android obesity in the general population, and in the absence of familial study, the causative link between mutation and phenotype cannot be formally established. Nevertheless, altered lamina architecture observed in mutated fibroblasts are responsible for premature cellular senescence and could contribute to the phenotype observed in this patient.
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PMID:A Heterozygous ZMPSTE24 Mutation Associated with Severe Metabolic Syndrome, Ectopic Fat Accumulation, and Dilated Cardiomyopathy. 2712 Jun 22