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11.
Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency 总被引:1,自引:0,他引:1
Hong YS; Kerr DS; Craigen WJ; Tan J; Pan Y; Lusk M; Patel MS 《Human molecular genetics》1996,5(12):1925-1930
An infant girl with elevated blood lactate, pyruvate, and plasma
branched-chain amino acids was diagnosed with dihydrolipoamide
dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4)
deficiency. Activities of the pyruvate dehydrogenase complex and E3 from
patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in
cultured skin fibroblasts, respectively. Western blot analysis demonstrated
that the amount of E3 protein in fibroblasts from the patient and her
father was about half of controls, while Northern blot analysis showed
normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs
from the patient revealed two mutations in separate alleles. One is a
single base insertion of an extra adenine in the last codon of the leader
peptide sequence (TAC-->TAAC) leading to a nonsense mutation which
results in the premature termination of the precursor E3 polypeptide
(Y35X). The other is a missense mutation due to substitution of guanine for
adenine, causing an Arg-->Gly substitution at amino acid 460 of the
mature protein (R460G) which triggers the loss of E3 activity probably by
structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the
parents demonstrated that the nonsense mutation was inherited from the
father and the missense mutation was inherited from the mother.
相似文献
12.
Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee. 相似文献
13.
Suleman MA Yole D Wango E Sapolsky R Kithome K Carlsson HE Hau J 《In vivo (Athens, Greece)》1999,13(1):25-27
Capture and prolonged confinement of wild African green monkeys (AGM, C. aethiops) in single housing have been shown to result in high morbidity and mortality. The present study was designed to analyse immune modulation associated with these procedures in AGMs. Four wild resting AGMs were stunned with a rifle shot as controls (group I). Seven newly captured monkeys (group II) and seven laboratory conditioned monkeys (group III) housed singly were anaesthetised with ketamine hydrochloride on day 18 and 45, and 180 and 210 post-capture, respectively. Heparinized blood (10 ml) was drawn from each animal and lymphocytes were cultured in six wells per sample. A triplicate subset was stimulated with 10 microliters Concanavalin A for 48 hours. The cells were pulsed with tritiated thymidine and harvested on filter discs 18 hours later. Lymphocyte stimulation indices (stimulated cell count-unstimulated cell count) were 3598 in group I. 3843 and 4395 in group II and 2809 and 2196 in group III, respectively. This indicates that AGMs confined to single housing for a prolonged period exhibit immune suppression. The results confirm our previous findings that the AGM is more susceptible to stress associated with immune suppression and subsequent high frequency of infectious diseases than other East African nonhuman primates confined to laboratory housing. 相似文献
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Dr. Michèle Gue BS Jean Fioramonti DS Jacques Frexinos MD M. Alvinerie BS Lionel Bueno DS 《Digestive diseases and sciences》1987,32(12):1411-1417
The effects of acoustic stress (AS) on gastrointestinal motility and their prevention by previous treatment with naloxone, phentolamine, propranolol, muscimol, and diazepam were investigated in intact and vagotomized fasted dogs fitted with chronically implanted strain gauges on the antrum at 10 cm from pylorus and on the jejunum at 70 and 140 cm from the pylorus. These effects were compared to those produced by intracerebroventricular administration of ovine corticotropin releasing factor (oCRF). Beginning 40–50 min after the occurrence of a gastric migrating motor complex (MMC), a 1-hr hearing of prerecorded intense music through earpieces (<100 dB) delayed the occurrence of the next gastric MMC observed after 2.8±1.2 hr, while jejunal MMC were still present at a normal frequency. During AS, heart rate and plasma cortisol were significantly increased by 32.7 and 215%, respectively, 10–15 min after the beginning of hearing. The AS-induced lengthening of the gastric MMC cycle as well as cortisol increase were abolished after previous administration of diazepam (0.5 mg/kg intramuscular) or muscimol (10 g/kg intravenous), while they were still present after naloxone (0.1 mg/kg intravenous), phentolamine (0.2 mg/kg intravenous), or propranolol (0.1 mg/kg intravenous). CRF administered intracerebroventricularly (100 ng/kg) also delayed the occurrence of gastric MMC without affecting jejunal motility, and this effect was not antagonized by previous treatment with diazepam or muscimol. Both the effects of AS and CRF were abolished after bilateral thoracic vagotomy. These results suggest that the selective inhibition of gastric motility induced by noise in dog is due to the CNS release of CRF which affects, in turn, the vagal output to the stomach. The suppressive action of diazepam or GABA agonist on noise-induced gastric hypomotility may be related to blockade of the AS-induced CRF release. 相似文献
19.
To clarify the defective erythropoiesis in eight patients with Diamond- Blackfan anemia, we studied their bone marrow response in vitro to recombinant human interleukin-3 (IL-3) and recombinant granulocyte- macrophage colony-stimulating factor (GM-CSF). In an erythropoietin- containing assay system, specimens from six of the eight patients yielded low numbers of erythroid colonies compared to control values, and in five of these no erythropoietin dose-response could be elicited. Addition of IL-3, GM-CSF or both to cultures from the six patients had no effect on CFU-E-derived colonies. In contrast, IL-3 but not GM-CSF induced a marked increase in the number (183%) and size of the BFU-E- derived colonies in five of the six cases and partially corrected the impaired dose-response to erythropoietin in four. Bone marrow from the other two patients yielded numbers of CFU-E and BFU-E colonies comparable to controls and manifested similar increments in colonies with increasing concentrations of erythropoietin. When IL-3 was added to these cultures, further increments were observed in the number and size of BFU-E colonies. We conclude that IL-3 enhanced the marrow erythropoiesis in most of the patients and exerted a corrective effect on the aberrant colony formation in the presence of erythropoietin. The data raise the possibility of IL-3 as a therapeutic agent in Diamond- Blackfan anemia. 相似文献
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