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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
13.
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
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Eun Jung Jung Ju-Yeon Kim Jae-Myung Kim Han Shin Lee Seung-Jin Kwag Ji-Ho Park Taejin Park Sang-Ho Jeong Chi-Young Jeong Young-Tae Ju Young-Joon Lee Soon-Chang Hong 《Medicine》2021,100(11)
This study evaluated the outcomes and prognostic factors for breast cancer according to initial lymph node (LN) status. Among patients with LN-negative breast cancer, we also focused on the prognostic value of estrogen receptor (ER) status.Medical records were retrospectively reviewed for 715 patients who underwent curative surgery for breast cancer between January 2005 and December 2015 at a single Korean institution. We evaluated factors that were associated with metastasis-free survival (MFS) according to LN status.Among the 715 patients (age: 28–87 years), 458 patients (64.1%) did not have axillary LN metastasis. Relative to patients without LN metastasis, patients with LN metastasis had larger tumor sizes and higher histological grades. Among patients with no LN metastasis, ER positivity was associated with non-significantly poorer MFS than ER negativity (mean survival: 138.90 months vs. 146.99 months, p = .17), and patients with LN-negative ER-positive disease had MFS rates of 91.7% at 5 years and 74.5% at 10 years. Among patients with LN-negative ER-positive disease, a poor prognosis was significantly associated with larger tumor size (≥2 cm, P = .03) and older age (≥50 years, P = .03).These results indicate that the risk of metastasis increases over time for patients with LN-negative ER-positive breast cancer, and especially for older patients or patients with larger tumors. 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
20.
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