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1.
Systemic deficiency of glutathione in cystic fibrosis 总被引:9,自引:0,他引:9
Roum J. H.; Buhl R.; McElvaney N. G.; Borok Z.; Crystal R. G. 《Journal of applied physiology》1993,75(6):2419-2424
2.
Galactorrhea was found in 5 patients with subclinical hypothyroidism. The galactorrhea consisted of the discharge of a few drops of milk only under pressure. Serum T4 was in the lower level of the normal range, but serum T3 was normal (T4: 6.3 +/- 1.2 micrograms/dl, T3: 113 +/- 7 ng/dl). Basal serum TSH and PRL were slightly increased only in 2 and 1 cases, respectively. The PRL responses to TRH stimulation were exaggerated in all cases, although the basal levels were normal. An enlarged pituitary gland was observed in 1 patient by means of CT scanning. All patients were treated by T4 replacement. In serial TRH tests during the T4 replacement therapy, the PRL response was still increased even when the TSH response was normalized. Galactorrhea disappeared when the patients were treated with an increased dose of T4 (150-200 micrograms/day). Recurrence of galactorrhea was not observed even though replacement dose of T4 was later decreased to 100 micrograms/day in 4 cases. In patients with galactorrhea of unknown origin, subclinical hypothyroidism should not be ruled out even when their serum T4, T3, TSH and PRL are in the normal range. The TRH stimulation test is necessary to detect an exaggerated PRL response, as the cause of the galactorrhea. To differentiate this from pituitary microadenoma, observation of the effects of T4 replacement therapy on galactorrhea is essential. 相似文献
3.
G Napolitano G Palka S Lio I Bucci P De Remigis L Stuppia F Monaco 《Annales de génétique》1990,33(1):9-15
In Down syndrome there is a high incidence of overt or subclinical hypothyroidism as well as some immunological defects, early thymic involution associated to low serum zinc levels. Zinc supplementation to the diet has been reported to transiently improve thymic function; moreover thymic function has been shown to be in relation with the pituitary-thyroid axis. The aim of this study was to evaluate if, in Down patients, zinc therapy could improve also thyroid function, by determining serum levels of total and free thyroid hormones and basal TSH levels. In 52 patients studied, we found a high incidence of subclinical hypothyroidism (30%); in 17 patients treated with zinc sulphate we showed a reduction of FT3. More significantly, we detected 9 patients with low zinc levels in which zinc supplementation improved thyroid function, thus reducing the incidence of subclinical hypothyroidism. 相似文献
4.
Protease activity in plasma is assayed using 4-methylumbelliferylguanidinobenzoate. The assay is modified by carrying out the reaction in the presence and absence of benzamidine, a competitive inhibitor of trypsin-like proteases. The parameters of the assay are described in detail. Using this assay, our earlier demonstration of a deficiency of protease activity in plasma of patients with cystic fibrosis is confirmed. The activity, corrected for the nonspecific hydrolysis of 4-methylumbelliferylguanidinobenzoate by benzamidine, is expressed as nanomoles of 4-methylumbelliferone released per milliliter plasma. Under standard conditions, the activity in plasma activated with chloroform-ellagic acid was 127.2 +/- 23.1 in 7 controls, 70.4 +/- 11.7 in 11 obligate heterozygotes, and 48.7 +/- 16.6 in 12 patients with cystic fibrosis. Identical results were obtained when unactivated plasma was used. These data demonstrate that the judicious use of specific inhibitors such as benzamidine might be useful in assaying low levels of protease activity in crude systems. 相似文献
5.
Eberhard Kauf Horst Dawczynski Gerhard Jahreis Evelyn Janitzky Klaus Winnefeld 《Biological trace element research》1994,40(3):247-253
The effectiveness of a peroral sodium selenite therapy (115 μg Se/m2 BSA/d) administered to cystic fibrosis patients (n=32) could after three months be identified in a significant serum selenium increase (0.69→0.96 μmol/L), a significant malondialdehyde
decrease (2.72→1.64 μmol/L), as well as in a significant serum vitamin E increase (4.31→5.72 μg/mL) Parallel to that, a serum
T3 increase as well as a highly significant decrease in the serum T4/T3-ratio were found, too, which point to improved peripheral T4→T3 conversion during selenium medication. Type-I-iodothyronine-5′-deiodinase has recently been identified as a specific selenoenzyme.
In the case of congenital hypothyroidism (n=37) application of sodium selenite in the above specified dosage yielded a mean serum selenium increase (0.87→1.12 μmol/L),
a not significant T3 increase (2.57→2.61 nmol/L) as well as a not significant TSH decrease (5.34→4.49 mIU/L) without an expected T4 decrease. With the serum lipids, however, a lowering of total cholesterol (4.85→4.53 mmol/L) simultaneous with a mean increase
in HDL-cholesterol (1.52→1.66 mmol/L) as well as a decrease in LDL-cholesterol (2.93→2.52) could be observed. We view the
reduction of the atherogenic serum lipid constellation in the course of selenium medication as an expression of increased
thyroid-hormone efficacy. 相似文献
6.
Verloo P Kocken CH Van der Wel A Tilly BC Hogema BM Sinaasappel M Thomas AW De Jonge HR 《The Journal of biological chemistry》2004,279(11):10316-10322
An inwardly rectifying anion channel in malaria-infected red blood cells has been proposed to function as the "new permeation pathway" for parasite nutrient acquisition. As the channel shares several properties with the cystic fibrosis transmembrane conductance regulator (CFTR), we tested their interrelationship by whole-cell current measurements in Plasmodium falciparum-infected and uninfected red blood cells from control and cystic fibrosis (CF) patients. A CFTR-like linear chloride conductance as well as a malaria parasite-induced and a shrinkage-activated endogenous inwardly rectifying chloride conductance with properties identical to the malaria-induced channel were all found to be defective in CF erythrocytes. Surprisingly, the absence of the inwardly rectifying chloride conductance in CF erythrocytes had no gross effect on in vitro parasite growth or new permeation pathway activity, supporting an argument against a close association between the Plasmodium-activated chloride channel and the new permeation pathway. The functional expression of CFTR in red blood cells opens new perspectives to exploit the erythrocyte as a readily available cell type in electrophysiological, diagnostic, and therapeutic studies of CF. 相似文献
7.
Multiple mutations in highly conserved residues are found in mildly affected cystic fibrosis patients 总被引:49,自引:0,他引:49
We have identified three different point mutations in the coding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Each mutation segregates with the disease in two- or three-generation pedigrees and is not found on the normal chromosome of any documented cystic fibrosis carrier. One of the mutations is found in two independent families that contain at least one individual with a mild course of disease. All of these alterations replace charged amino acids with less polar residues and are found in the putative transmembrane sections of the molecule. The mutated amino acids are found to be conserved in both rodents and amphibians and lie in a region of CFTR that is believed to form a channel in the membrane. Although these alterations are rare, they provide important clues to functionally important regions of the molecule. 相似文献
8.
Transient subclinical hypothyroidism in early pregnancy 总被引:10,自引:0,他引:10
K Kamijo T Saito M Sato A Yachi A Mukai M Fukusi N Takasugi 《Endocrinologia japonica》1990,37(3):397-403
In the present study, a new clinical state of transient subclinical hypothyroidism in 12 early pregnant women is documented. The incidence of transient subclinical hypothyroidism was 18 (0.19%) among 9,453 pregnant women examined in this series in Sapporo. The characteristics of transient subclinical early gestational hypothyroidism in our study may be summarized as follows: temporarily increased TSH in the blood (11.7 +/- 6.3 microU/ml; mean +/- S.D.) in early pregnant women at 8.5 +/- 2.4 weeks of gestation, accompanied with or without reduced FT4 which spontaneously return to normal at 17.9 +/- 7.1 weeks; no subjective complaints and no previous history of thyroid disease; small struma; positive titers of antimicrosome antibody and antithyroglobulin antibody; normal serum hCG; negative results for TSH receptor antibody. None of the infants show any physical abnormality such as struma and none of the patients had neck pain or fever suggesting subacute thyroiditis. The presence of autoantibody to the thyroid gland and echographical findings strongly suggest the existence of Hashimoto's thyroiditis in early pregnant women with transient subclinical hypothyroidism, although the cause of transient subclinical early gestational hypothyroidism remains obscure. 相似文献
9.
Inside-out vesicles (10) were prepared from red cells obtained from cystic fibrosis (CF) patients and approximately aged-matched controls. Ca2+-uptake activity was found to be significantly reduced in the preparations derived from CF patients. This reduction was apparent at all time points studied (10 sec-120 min) and at all free calcium concentrations used (10–150 μM). Reciprocal plots of the data revealed that the Kdiss for calcium of the calcium pump, was similar in control and CF samples but that the VCa2+ was significantly reduced (P<0.001) in the CF preparations. Calmodulin prepared from red cell hemolysates of controls was found to stimulate Ca2+-transport activity to a similar extent in both CF and control samples. 相似文献
10.
11.
Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%. 总被引:2,自引:0,他引:2
M Macek Jr A Mackova A Hamosh B C Hilman R F Selden G Lucotte K J Friedman M R Knowles B J Rosenstein G R Cutting 《American journal of human genetics》1997,60(5):1122-1127
Cystic fibrosis (CF)--an autosomal recessive disorder caused by mutations in CF transmembrane conductance regulator (CFTR) and characterized by abnormal chloride conduction across epithelial membranes, leading to chronic lung and exocrine pancreatic disease--is less common in African-Americans than in Caucasians. No large-scale studies of mutation identification and screening in African-American CF patients have been reported, to date. In this study, the entire coding and flanking intronic sequence of the CFTR gene was analyzed by denaturing gradient-gel electrophoresis and sequencing in an index group of 82 African-American CF chromosomes to identify mutations. One novel mutation, 3120+1G-->A, occurred with a frequency of 12.3% and was also detected in a native African patient. To establish frequencies, an additional group of 66 African-American CF chromosomes were screened for mutations identified in two or more African-American patients. Screening for 16 "common Caucasian" mutations identified 52% of CF alleles in African-Americans, while screening for 8 "common African" mutations accounted for an additional 23%. The combined detection rate of 75% was comparable to the sensitivity of mutation analysis in Caucasian CF patients. These results indicate that African-Americans have their own set of "common" CF mutations that originate from the native African population. Inclusion of these "common" mutations substantially improves CF mutation detection rates in African-Americans. 相似文献
12.
B. Strandvik E. Svensson H. W. Seyberth 《Prostaglandins, leukotrienes, and essential fatty acids》1996,55(6):419-425
The urinary excretion rate (ng/h/1.73 m2) of prostanoids was determined with a capillary gas-liquid chromatographic mass spectrometric method in 19 patients with cystic fibrosis (CF) aged 1–29 years. Patients with CF showed an increased excretion of prostaglandin E2 metabolites (PGE-M) and thromboxane B2 and its metabolites at all ages. An imbalance in the excretion pattern of thromboxane B2 metabolites also suggested a relative impairment of β-oxidation. There was no increased excretion of dinor-6-keto-PGF1α, indicating normal prostacyclin biosynthesis. No correlation was found to genotype, clinical score, lung function or bacterial colonization but a significant negative relation was found between the main prostanoids in the urine and serum phospholipid levels of essential fatty acids. The results show that, contrary to the generally accepted decrease of prostanoid excretion in essential fatty acid deficiency, patients with CF increase their production parallel to the development of the deficiency. Since prostanoid synthesis is rate limited by arachidonic acid release, our data support a previously presented hypothesis about a pathological regulation of the release of arachidonic acid in CF. 相似文献
13.
Mendes F Roxo Rosa M Dragomir A Farinha CM Roomans GM Amaral MD Penque D 《Biochemical and biophysical research communications》2003,311(3):665-671
A561E, a novel cystic fibrosis (CF) associated mutation in the first nucleotide binding domain of CFTR, is the second most common CF mutation in Portugal. Properties of the A561E-CFTR protein were studied by immunoblotting, pulse-chase, immunocytochemistry, and MQAE halide-efflux assay in stably transfected BHK cells. Altogether, results presented here suggest that A561E causes protein mislocalization in the endoplasmic reticulum where the mutant protein must be trapped by the quality control mechanism. We conclude that A561E originates a protein trafficking defect, thus belonging to class II of CFTR mutations. As it is the case for F508del-CFTR (the most common CF mutant), low temperature treatment partially rescues a functional A561E-CFTR channel, suggesting that substitution of glutamic acid for alanine at position 561 does not completely abolish CFTR function. Pharmacological strategies previously reported for treatment of CF patients with the F508del mutation could thus be also effective in CF patients bearing the A561E mutation. 相似文献
14.
T Onay J Zielenski O Topaloglu N Gokgoz H Kayserili M Y Apak Y Camcioglu H Cokugras N Akcakaya L C Tsui B Kirdar 《Human biology; an international record of research》2001,73(2):191-203
Identification of mutations causing cystic fibrosis (CF) in the Turkish population is essential for assessment of the molecular basis of CF in Turkey and the development of strategies for prenatal diagnosis and genetic counseling. Here, we present an updated report of mutations found in the Turkish CF population from an extensive screening study of the entire coding region, including exon-intron boundaries and the promoter region. Cases for which mutations could not be identified were also screened for previously defined large alterations and (TG)mTn-M470V loci. This study revealed a total of 27 different mutations accounting for almost 60% of disease genes in the Turkish population. In this study, we also identified the haplotypes associated with 17 mutations and those associated with unknown mutations. The mutation spectrum of CF in Turkey and its associated haplotypes indicated the presence of a major Mediterranean component in the contemporary Turkish population. 相似文献
15.
G M Cabello J L Cabello EH Jr O Fernande A Harris 《Human biology; an international record of research》2001,73(3):403-409
Cystic fibrosis patients from Rio de Janeiro, Brazil, were screened for mutations in exons 11 and 16 of the cystic fibrosis transmembrane conductance regulator gene (CFTR) by a nonradioactive single-stranded conformational polymorphism (SSCP) analysis technique. This procedure was used to evaluate the undefined mutations in one or both alleles of 64 cystic fibrosis patients. Unusual SSCP profiles were investigated further by sequence analysis. Two patients were shown to carry the G542X mutation (exon 11) and five had the splicing mutation 3120+1G-->A(intron 16), one of them being homozygous for the mutation. This is the first report of the 3120+ IG-->A mutation in Brazil. where it appears to be a frequent disease-associated molecular alteration in the CFTR gene. 相似文献
16.
Three female children presented with different clinical symptoms that could be related to impaired thyroid function. They
underwent an accurate pediatric-endocrinologic diagnosis. Laboratory tests revealed no pathological findings, except latent
hypothyroidism and selenium deficiency. Hypothyroidism was diagnosed by elevated basal TSH and by a pathological iv-TRH-stimulation
test. After treating the children with sodium selenite orally for 4 wk, their metabolism had returned to normal and we saw
a marked improvement of all clinical symptoms. For the first time, we have been able to describe hypothyroidism caused exclusively
by selenium deficiency, the pathophysiology of which may be expressed as a malfunction of human 5′-deiodinases. 相似文献
17.
Relationship of decreased hepatic lipase activity and lipoprotein abnormalities to essential fatty acid deficiency in cystic fibrosis patients 总被引:1,自引:0,他引:1
E Lévy G Lepage M Bendayan N Ronco L Thibault N Galéano L Smith C C Roy 《Journal of lipid research》1989,30(8):1197-1209
Polyunsaturated fatty acids are known to affect plasma lipids and lipoproteins but there is no information on the effect of essential fatty acid (EFA) deficiency on lipoprotein composition. The purpose of this study was to characterize lipoproteins from 17 cystic fibrosis (CF) patients in relationship to their EFA status (eicosatrienoic/arachidonic acid ratio) and compare them with those of 10 healthy siblings (SIB) and of 10 unrelated controls. In 7 EFA-deficient (EFAD) and 10 EFA-sufficient (EFAS) patients, hypocholesterolemia was associated with a decrease of HDL-cholesterol and of LDL-cholesterol which was more marked in the EFAD group. Similarly, although triglyceride enrichment of VLDL, LDL, HDL2, and HDL3 with a concomitant reduction of cholesteryl esters from all particles except HDL2 was observed in both CF groups, it was more sizable in the EFAD patients. These changes led to an increase in the particle size of VLDL, LDL, and HDL2 whereas the distribution of HDL3 was skewed to smaller particles. Alterations in the apoprotein composition of particles were greater in EFAD than in EFAS. A decrease of total postheparin lipolytic activity was observed in the two groups of CF patients as well as in siblings. It was entirely accounted for by hepatic lipase (mumol FFA/ml per h) which was more severely diminished in EFAD (2.8 +/- 0.6) than in EFAS (4.4 +/- 0.7) and SIB (5.1 +/- 0.5). Although the two groups of CF children differed in terms of growth, severity of malabsorption, and vitamin E status, these data suggest that disturbance of lipoprotein concentration, composition, size, and metabolism (hepatic lipase) may be in part related to EFA deficiency. Further studies are necessary to explore the effect of EFA deficiency on hepatic lipase activity. 相似文献
18.
《Biochemical medicine》1978,19(2):294-297
The levels of serum pancreatic-type ribonuclease (RNase) activity in normal individuals and in individuals homozygous and heterozygous for the cystic fibrosis (CF) gene have been studied. In 21 CF patients, ages 3–24 years, RNase levels of 459 ± 95 units/ml did not differ significantly from the RNase levels of 467 ± 105 units/ml in 17 normal individuals of the same age group nor from those of 490 ± 52 units/ml in 5 individuals heterozygous for the CF gene. 相似文献
19.
Minarowski Ł Sands D Minarowska A Karwowska A Sulewska A Gacko M Chyczewska E 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2008,46(2):245-246
Thiocyanates (SCN-) are ubiquitous in nature. There are indispensable part of host defense system that act as a substrate for lactoperoxidase (LPO). In our study we present initial data on SCN- concentration in saliva of CF patients in comparison to healthy non-smokers and healthy smokers. 5 ml of saliva was collected from each subject to a sterile tube and thiocyanate concentration was measured in each sample. The results of the measurements are presented on Fig. 1. Mean concentration of SCN- in saliva of CF patients was 0.031 +/- 0.0052 g/l, in healthy non-smokers 0.039 +/- 0.0048 g/l and in healthy smokers 0.048 +/- 0.0161 g/l. The differences between each group were statistically significant. Studies on larger group of patients and probably on different material (BALF or induced sputum) should present interesting data complementing the in vitro studies. 相似文献
20.
Leucocytes from 26 patients with cystic fibrosis (CF) and 18 healthy controls were investigated by migration inhibition induced by a variety of antigens. In patients with CF cell-mediated immunity was found to human lung and pancreatic tissue extracts as well as to Aspergillus fumigatus, Pseudomonas aeruginosa, and food antigens but not to brain, heart, or kidney. Those patients with the severest form of the disease had the greatest impairment of cell-mediated immunity, but this impairment could be reversed by steroid treatment. Cell-mediated cytotoxicity may also be concerned in the pathogenesis of CF. 相似文献