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101.
Genetics of the low density lipoprotein receptor: 总被引:1,自引:0,他引:1
Fibroblast association (plasma membrane binding plus intracellular accumulation) and degradation of radioiodinated low density lipoprotein (125I-LDL) index plasma membrane LDL receptor activity. Cultured fibroblasts from 23 subjects affected with familial hypercholesterolemia (HC) and from 95 subjects without HC (non-HCs) were tested for 125I-LDL association and degradation. Both LDL receptor activity indices were twice as high in non-HC and HC heterozygous cell strains. This is compatible with a major gene effect on LDL receptor activity. However, a considerable overlap between non-HC and HC heterozygous values was found in the 125I-LDL association assay [median (range) 970 (330-2500), and 450 (250-490), respectively] and in the degradation assay [median (range) 810 (280-2020), and 470 (160-790), respectively]. The values are expressed as ng 125I-LDL X mg cell protein-1 X 4.5 h-1. These great overlaps in the LDL receptor activity indices support the view that the influence of LDL receptor activity on the HC phenotype may be smaller than believed previously. Furthermore, for the diagnosis of HC, these LDL receptor activity assays are far more expensive and have less sensitivity and specificity than simple serum cholesterol determination. The LDL receptor-dependent 125I-LDL association values for the HC heterozygous individuals clustered into four groups. Family data supported the hypothesis that this variation could be due to four different LDL receptor variants, each coded for by different alleles at the LDL receptor locus. If confirmed, this finding may have implications for the understanding of the variable expression of HC and also of the genetic impact on lipoprotein metabolism and susceptibility to atherosclerosis in non-HCs. 相似文献
102.
OBJECTIVE: To describe the clinical picture, pathophysiology, and treatment of concomitant lesions of the peroneus brevis tendon and lateral ligament injuries to the ankle. BACKGROUND: In some cases, chronic lateral ankle instability is associated with a longitudinal partial tear in the peroneus brevis tendon. Patients who suffer from this lesion usually have atypical posterolateral ankle pain combined with signs of recurrent ligament instability ("giving way"). The tendon injury is often overlooked because it is combined with the ligament injury, and the injury mechanisms are similar. DESCRIPTION: Tears or laxity in the superior peroneal retinaculum allow the anterior part of the injured peroneus brevis tendon to ride over the sharp posterior edge of the fibula, leading to a longitudinal tear in the tendon. This combined injury should be suspected in patients with recurrent giving way of the ankle joint and retromalleolar pain. The diagnosis can be established using either ultrasonography or magnetic resonance imaging. DIFFERENTIAL DIAGNOSIS: Ligament injury, tenosynovitis, peroneus longus tendon lesion, os peroneum fracture, distal peroneus brevis tendon tear, or anomalous peroneus tertius tendon. TREATMENT: The tendon injury and the ligament insufficiency should be repaired at the same time. CONCLUSIONS: We recommend reconstruction of the superior peroneal retinaculum, combined with repair of the tendon, using side-to-side sutures and anatomical reconstruction of the lateral ankle ligaments. 相似文献
103.
104.
Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder and is traditionally classified into two major types, CMT type 1 (CMT1) and CMT type 2 (CMT2). Most CMT1 patients are associated with the duplication of 17p11.2-p12 (CMT1A duplication) and small numbers of patients have mutations of the peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), connexin 32 (Cx32/GJB1), and early growth response 2 (EGR2) genes. Some mutations of MPZ and Cx32 were also associated with the clinical CMT2 phenotype. We constructed denaturing gradient gel electrophoresis (DGGE) analysis as a screening method for PMP22, MPZ, and Cx32 mutations and studied 161 CMT patients without CMT1A duplication. We detected 27 mutations of three genes including 15 novel mutations; six of PMP22, three of MPZ, and six of Cx32. We finally identified 21 causative mutations in 22 unrelated patients and five polymorphic mutations. Eighteen of 22 patients carrying PMP22, MPZ, or Cx32 mutations presented with CMT1 and four of them with MPZ or Cx32 mutations presented with the CMT2 phenotype. DGGE analysis was sensitive for screening for those gene mutations, but causative gene mutation was not identified in many of the Japanese patients with CMT, especially with CMT1. Other candidate genes should be studied to elucidate the genetic basis of Japanese CMT patients. 相似文献
105.
The behavioural response to intrathecal i.th. serotonin (5-HT) was examined in mice pretreated with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) which produce similar extensive depletion of central 5-HT levels. Intrathecal 5-HT (0.4 micrograms) elicited a behavioural response consisting of reciprocal hindlimb scratching and biting or licking of the hindquarters indicative of nociceptive stimulation. The response to i.th. 5-HT was markedly increased 5 days after intracerebroventricular (i.c.v.) injection of 5,7-DHT (80 micrograms base per mouse). On the other hand, 24 h after the last pretreatment injection of PCPA (400 mg kg-1 for 6 consecutive days), the response to i.th. 5-HT was unaltered. These results indicate that i.c.v. 5,7-DHT produces supersensitivity to 5-HT. Since PCPA failed to alter the effect of 5-HT, the supersensitivity seems not to be due to depletion of 5-HT levels after the lesion. 相似文献
106.
Per H.B. Carstens MD Cyrus Ghazi MD Robert H. Carnighan MD PhD McHenry S. Brewer MD 《Human pathology》1986,17(12):1282-1285
Biliary tract obstruction in a 30-year-old man was found to be caused by a malignant melanoma in the common bile duct. Melanin pigment was demonstrated by immunohistochemistry and electron microscopy. Extensive search for a primary malignant melanoma elsewhere was unsuccessful. No pigmented lesions had been removed previously. There were junctional changes in the mucosa of the common bile duct close to the tumor. The malignant melanoma in the common bile duct therefore is considered to be primary. Only one other case of primary malignant melanoma in the common bile duct has been described in the literature, whereas metastases to the major bile ducts in one autopsy study of malignant melanoma in the more common locations were found with a frequency of 6 per cent. 相似文献
107.
The effect of a cold pressor test (CPT) on haemodynamics in relation to general and regional sympathetic activity and arginin vasopressin (AVP), was studied in eleven patients with severe congestive heart failure (CHF). Compared to an age-matched control group (C), resting arterial plasma noradrenaline (NA) (419 +/- 77 vs. 182 +/- 15 pg ml-1), and adrenaline (A) (142 +/- 28 vs 54 +/- 10 pg ml-1) were higher (P less than 0.05) in CHF. AVP showed no significant difference (14 +/- 4 vs. 9 +/- 4 pg ml-1). During CPT systolic and diastolic blood pressure and systemic vascular resistance increased (P less than 0.01), as did NA (delta 114 +/- 39 pg ml-1, P less than 0.01), A (delta 33 +/- 10 pg ml-1, P less than 0.01) and heart rate (delta 10 beats min-1, P less than 0.01). The myocardial v-a difference of NA decreased (P less than 0.05), but was unchanged across the renal vascular bed during CPT. The a-v difference of NA in the hepatic vascular bed, and fractional extraction of A in the coronary sinus, renal and hepatic vascular beds remained unchanged during CPT. AVP did not change significantly and no change in cardiac index or left ventricular filling pressure was observed during CPT. These data suggest that despite an increased activation of the sympathetic nervous system at rest, a further increase in blood pressure and catecholamines took place during CPT. Thus, the effect of a CPT which activates the central sympathetic system seems not to be altered in patients with severe CHF. 相似文献
108.
The effects of catecholamines on histamine release from rat peritoneal mast cells, was studied in an in vitro system. It was found that norepinephrine (10–5–10–3
M) exerts a significant, dose related, repressive effect on compound 48/80-induced histamine release. This effect is greatly potentiated by -antagonists and is noticeable throughout the concentration range 10–11–10–3
M norepinephrine. Phentolamine diminishes the repressive effect that norepinephrine shows at 10–5
M.Norepinephrine (10–5
M) totally inhibits the progressive histamine release induced by both compound 48/80 and strontium (10 M) in non-Ca2+-depleted cells. The release that is dependent on extracellular calcium is inhibited by norepinephrine.The repressive effect of norepinephrine at 10–3 is counteracted by 5.6 mM
d-glucose, 2-deoxyglucose abolishes this effect. The repression of histamine release by 10–5
M norepinephrine is not influenced byd-glucose.These results suggest that the effects on histamine release, observed within a low concentration range of norepinephrine (<10–3
M), may be due to -adrenoreceptor mechanisms and an interference in transmembrane calcium transport. Our data further suggest that norepinephrine at 10–3
M may inhibit oxidative phosphorylation.Isoproterenol and epinephrine (10–9–10–5
M) show little effect on 48/80-induced histamine release in a normal medium. However, when calcium is excluded from the medium, histamine release is potentiated. These results seem to indicate that isoproterenol and epinephrine act by displacing intracellular calcium, making it available for the exocytosis process. 相似文献
109.
The disposition of the plasticizer di-(2-ethylhexyl) phthalate (DEHP) and four of its major metabolites was studied in male rats given single infusions of a DEHP emulsion in doses of 5, 50 or 500 mg DEHP/kg body weight. Plasma concentrations of DEHP and metabolites were followed for 24 h after the start of the infusion. The kinetics of the primary metabolite mono-(2-ethylhexyl) phthalate (MEHP) was studied separately.The concentrations of DEHP in plasma were at all times considerably higher than those of MEHP, and the concentrations of MEHP were much higher than those of the other investigated metabolites. In animals given 500 mg DEHP/kg, the areas under the plasma concentration-time curves (AUCs) of the other investigated metabolites were at most 15% of that of MEHP. Parallel decreases in the plasma concentrations of DEHP, MEHP and the and (-1) oxidized metabolites indicated that the elimination of DEHP was the rate-limiting step in the disposition of the metabolites. This was partly supported by the observation that the clearance of MEHP was higher than that of DEHP. Nonlinear increases in the AUCs of DEHP and MEHP indicated saturation in the formation as well as the elimination of the potentially toxic metabolite MEHP. 相似文献
110.
Radiographic quantification of alveolar bone level changes 总被引:3,自引:0,他引:3
Jasim M. Albandar Jostein Rise Per Gjermo Jan R. Johansen 《Journal of clinical periodontology》1986,13(3):195-200
The "random burst" theory has recently been proposed as an explanation of the pattern of periodontal disease progression. The theory predicts that the progression of bone loss at individual sites is not dependent upon previous bone loss and age. A longitudinal radiographic study was designed to test this hypothesis, and to describe the changes in bone level over 2 years in a group of 180 subjects (18-68 years of age) who were not under systematic periodontal treatment. The results indicated that 94% of the sites did not show significant changes in the alveolar bone level during the observation period. The mean annual bone loss for the total population was 0.11 mm. By regressing longitudinal bone loss upon age, it was shown that the rate of bone loss increased rapidly between 33 and 56 years of age while a different pattern was shown for the age intervals 18-32 and 57-68 years. Also, the rate of bone loss increased with increasing initial bone loss. This was less evident in the oldest age group. It was concluded that the progression of bone loss in the present material is consistent with a "burst" theory. However, the progression did not occur randomly with regard to previous loss of alveolar bone and time. 相似文献