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11.
Mykkänen J Torrents D Pineda M Camps M Yoldi ME Horelli-Kuitunen N Huoponen K Heinonen M Oksanen J Simell O Savontaus ML Zorzano A Palacín M Aula P 《Human molecular genetics》2000,9(3):431-438
Lysinuric protein intolerance (LPI; MIM 222700) is an autosomal recessive disorder characterized by defective transport of the cationic amino acids lysine, arginine and ornithine at the basolateral membrane of the polar epithelial cells in the intestine and renal tubules, and by hyperammonemia after high-protein meals. LPI is caused by mutations in the SLC7A7 (solute carrier family 7, member 7) gene encoding y(+)LAT-1 (y(+)L amino acid transporter-1), which co-induces together with 4F2 heavy chain (4F2hc) system y(+)L in Xenopus oocytes. All Finnish LPI patients share the same founder mutation 1181-2A-->T (LPI(Fin)) not found in LPI patients elsewhere. Mutation screening of 20 non-Finnish LPI patients revealed 10 novel mutations: four deletions, two missense mutations, two nonsense mutations, a splice site mutation and a tandem duplication. Five LPI mutations (L334R, G54V, 1291delCTTT, 1548delC and LPI(Fin)) were studied functionally. All mutant proteins failed to co-induce amino acid transport activity when expressed with 4F2hc in Xenopus oocytes. Immunostaining experiments revealed that frameshift mutants 1291delCTTT, 1548delC and LPI(Fin)remained intracellular on expression with 4F2hc. In contrast, the missense mutants L334R and G54V reached the oocyte plasma membrane when co-expressed with 4F2hc, demonstrating that they are transport-inactivating mutations. This finding, together with the strong degree of conservation among all members of this family of amino acid transporters, indicates that residues L334 and G54 play a crucial role in the function of the y(+)LAT-1 transporter. 相似文献
12.
Risk of obstetric cholestasis in sisters of index patients 总被引:23,自引:0,他引:23
The aim of the present study was to evaluate the rate of intrahepatic cholestasis of pregnancy in first-degree relatives of index patients. Index patients (n=65) with singleton pregnancies complicated by intrahepatic cholestasis were identified among the women (n=11 984) who gave birth at Kuopio University Hospital in 1994-1998. The pregnancy histories of relatives of 56 index patients were reviewed and the rate of cholestasis in first-degree relatives was compared with that in the general obstetric population. Obstetric cholestasis was experienced by 9% of the parous sisters and 11% of the mothers of the index patients. The risk per delivery was 6% in the first-degree relatives. The rate in the general obstetric population was 0.54%. The odds ratios and 95% confidence intervals were 12.6 (5.6-28.1) for the sisters and 12.2 (6.2-24.2) for the mothers. Obstetric cholestasis clusters within some families and is under strong genetic influence, although the precise genetic pattern remains obscure. The sisters of index patients are at an increased risk of the disorder and may benefit from close obstetric care. 相似文献
13.
14.
Canine gastric glycoprotein antigens in early carcinogenesis 总被引:1,自引:0,他引:1
The effect of one single dose of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on the antigenic structures of gastric juice glycoproteins, was studied in dogs. Antisera to glycoproteins of the fetal alimentary canal were raised. Histologic mucosal specimens and glycoprotein fractions of gastric juice which were taken from four dogs during a 15.5-month period after MNNG administration, were examined immunohistologically and by immunodiffusion for the appearance of fetal-like antigens. Fetal-like structures appeared in a stepwise manner in both the acid and neutral glycoprotein fractions of the gastric juice, and showed gradual crossreactivity between macromolecules obtained from gastric juice samples obtained during the observation period. Eight immunizations carried out using physicochemically different glycoprotein fractions of fetal canine alimentary canal mucosa, produced a similar response, thus indicating that the same antigenic structures are incorporated into all mucus glycoproteins, even though they do differ physicochemically. It is suggested that this "omnipotential" incorporation picture could also be found after exposure to MNNG and is, by its nature, typically fetal. 相似文献
15.
Mattila A Miettinen A Heinonen PK 《Infectious diseases in obstetrics and gynecology》1994,1(6):265-268
Objective: The aim of the study was to determine the currently most frequent microbial findings in Bartholin's duct abscess.Methods: Computerized records of microbial findings of 249 cases of Bartholin's duct abscess were retrospectively studied.Results: In 129 cases, only 1 microbe and, in 117 cases, >1 microbe were recovered. In 3 cases, the flora was recorded as normal for the lower genital tract. Of all bacteria isolated, 252 were aerobic or facultative and 108 were anaerobic or microaerophilic. Aerobic or facultative bacteria alone caused 142 (57%) of the 249 cases, Escherichia coli being the most frequent isolate in this group. Anaerobic or microaerophilic bacteria alone caused 33 cases (13%), Bacteroides species and Prevotella species being most frequently identified. Both aerobic or facultative and anaerobic or microaerophilic bacteria were isolated in 70 cases (28%). Candida albicans alone caused 1 case of Bartholin's duct abscess. The sexually transmitted pathogens Neisseria gonorrhoeae and Chlamydia trachomatis were both involved in only 2 cases.Conclusions: Bartholin's duct abscess was mainly caused by opportunistic bacteria, and sexually transmitted pathogens were only rarely involved in its pathogenesis. Since potentially pathogenic bacterial species were also frequently isolated, the use of antibiotics to complement the surgical treatment of Bartholin's duct abscess seems advisable, especially in patients with systemic symptoms. 相似文献
16.
Vitamin C and other compounds in vitamin C rich food in relation to risk of tuberculosis in male smokers. 总被引:1,自引:0,他引:1
H Hemil? J Kaprio P Pietinen D Albanes O P Heinonen 《American journal of epidemiology》1999,150(6):632-641
To examine whether vitamin C rich food consumption and related vitamin C intake are associated with the risk of tuberculosis, the authors analyzed 167 incident cases of tuberculosis during a median follow-up time of 6.7 years in a clinical trial cohort of 26,975 Finnish men for whom they had baseline dietary data. A highly statistically significant inverse association between calculated vitamin C intake and the incidence of tuberculosis was found, but adjustment for non-dietary factors weakened the association to nonsignificant. Furthermore, the risk of tuberculosis decreased with increasing intake of fruits, vegetables, and berries independent of vitamin C intake. Subjects who had dietary vitamin C intake >90 mg/day and who consumed more than the average amount of fruits, vegetables, and berries had a significantly lower risk of tuberculosis (adjusted relative risk = 0.40; 95% confidence interval 0.24, 0.69). Associations between dietary vitamin C intake and occurrence of various diseases without proper control of confounding have often been interpreted as causal. These findings show that such associations can be confounded even by some other dietary components. Lower tuberculosis incidence in subjects who consumed more fruits, vegetables, and berries poor in vitamin C suggests that other compounds in such a diet may reduce the risk of tuberculosis. 相似文献
17.
OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age. 相似文献
18.
Context Many recent cross-sectional studies have suggested that lack of early exposure to communicable diseases, including measles, in affluent countries may have increased rates of atopic disease. Objective To study the association between natural measles infection and atopy. Design and Setting Cross-sectional nationwide study in Finland using data gathered between November 1, 1982, and June 30, 1986. Subjects A total of 547,910 individuals aged 14 months to 19 years who at the time of measles-mumps-rubella (MMR) vaccination had relevant information collected on the occurrence of measles and allergic rhinitis, eczema, and asthma. Main Outcome Measures Lifetime occurrence of atopic manifestations in subjects who had had measles compared with those who had not, expressed as age-specific and age-adjusted prevalence ratios. Results The age-adjusted prevalence ratio of atopic manifestations among those who had had measles (n = 20,690) compared with those who had not (n = 527,220) was 1.32 (95% confidence interval [CI], 1.27-1.36) for eczema, 1.41 (95% CI, 1.33-1.49) for rhinitis, and 1.67 (95% CI, 1.54-1.79) for asthma. The positive association between measles and atopy was evident at all ages, in both urban and rural dwellers, and among subjects with many or few contacts at home or in day care. Conclusions Based on our data, measles and atopy occur more frequently together than expected, which does not support the hypothesis that experiencing natural measles infection offers protection against atopic disease. 相似文献
19.
Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy 总被引:1,自引:0,他引:1
Koohestani N; Chia MC; Pham NA; Tran TT; Minkin S; Wolever TM; Bruce WR 《Carcinogenesis》1998,19(9):1679-1684
McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994)
and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the
striking similarity in lifestyle risk factors for colorectal cancer and
insulin resistance, proposed that the hyperinsulinemia, glycemia and
hypertriglyceridemia associated with insulin resistance promotes colon
cancer. To compare the effect of diet on colon cancer promotion and insulin
resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids
and energy in pairwise comparisons on average size of aberrant crypt foci
(ACF) and on glucose intolerance in the same animals in a single
experiment. Diets high in fat and energy increased and diets with increased
n-3 fatty acids and calorie restriction decreased both ACF growth and
glucose intolerance compared with control diets. The measures of promotion
of colon cancer and insulin resistance were strongly correlated (n = 98, r
= 0.67, P < 0.001). In addition, both were highly correlated with daily
energy intake (r = 0.62 and 0.66) and were also correlated with basal
(post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P <
0.01). We concluded that ACF growth and glucose intolerance are correlated
for a wide range of diets and that increased circulating energy (glucose
and triglycerides) may lead to both colon cancer promotion and insulin
resistance.
相似文献
20.
Home‐Based Exercise Training Improves Left Ventricle Diastolic Function in Survivors of Childhood ALL: A Tissue Doppler and Velocity Vector Imaging Study 下载免费PDF全文