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Biomedical subjects

S Simon

Publications and source records attributed to S Simon.

At least 55 records · Page 3Linked to original sources

Acute hypoxic pulmonary vasoconstriction in conscious dogs decreases renin and is unaffected by losartan.

Acute hypoxic pulmonary vasoconstriction (HPV) may be mediated by vasoactive peptides. We studied eight conscious, chronically tracheostomized dogs kept on a standardized dietary sodium intake. Normoxia (40 min) was followed by hypoxia (40 min, breathing 10% oxygen, arterial oxygen pressures 36 +/- 1 Torr) during both control (Con) and losartan experiments (Los; iv infusion of 100 microg. min-1. kg-1 losartan). During hypoxia, minute ventilation (by 0.9 l/min in Con, by 1.3 l/min in Los), cardiac output (by 0.36 l/min in Con, by 0.30 l/min in Los), heart rate (by 11 beats/min in Con, by 30 beats/min in Los), pulmonary artery pressure (by 9 mmHg in both protocols), and pulmonary vascular resistance (by 280 and 254 dyn. s. cm-5 in Con and Los, respectively) increased. Mean arterial pressure and systemic vascular resistance did not change. In Con, PRA decreased from 4.2 +/- 0.7 to 2.5 +/- 0.5 ng ANG I. ml-1. h-1, and plasma ANG II decreased from 11.9 +/- 3.0 to 8.2 +/- 2.1 pg/ml. The renin-angiotensin system is inhibited during acute hypoxia despite sympathetic activation. Under these conditions, ANG II AT1-receptor antagonism does not attenuate HPV.

Angiotensin II↗

Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen.

Extracts of Hypericum perforatum (St. John's wort) are used in the treatment of depression. They contain the plant pigment hypericin and hypericin derivates. These compounds have light-dependent activities. In order to estimate the potential risk of phototoxic skin damage during antidepressive therapy, we investigated the phototoxic activity of hypericin extract using cultures of human keratinocytes and compared it with the effect of the well-known phototoxic agent psoralen. The absorbance spectrum of our Hypericum extract revealed maxima in the whole UV range and in parts of the visible range. We cultivated human keratinocytes in the presence of different Hypericum concentrations and irradiated the cells with 150 mJ/cm2 UVB, 1 J/cm2 UVA or 3 h with a white light of photon flux density 2.6 mumol m-2 s-1. The determination of the bromodeoxyuridine incorporation rate showed a concentration- and light-dependent decrease in DNA synthesis with high hypericin concentrations (> or = 50 micrograms/mL) combined with UVA or visible light radiation. In the case of UVB irradiation a clear phototoxic cell reaction was not detected. We found phototoxic effects even with 10 ng/mL psoralen using UVA with the same study design as in the case of the Hypericum extract. These results confirm the phototoxic activity of Hypericum extract on human keratinocytes. However, the blood levels that are to be expected during antidepressive therapy are presumably too low to induce phototoxic skin reactions.

Antidepressive Agents↗

A four-to-one association between peptide motifs: four C-terminal domains from cholinesterase assemble with one proline-rich attachment domain (PRAD) in the secretory pathway.

The major type of acetylcholinesterase in vertebrates (AChET) is characterized by the presence of a short C-terminal domain of 40 residues, the 'tryptophan amphiphilic tetramerization' (WAT) domain. The presence of this domain is not necessary for catalytic activity but is responsible for hydrophobic interactions and for the capacity of AChET subunits to form quaternary associations with anchoring proteins, thereby conditioning their functional localization. In the collagen tail of asymmetric forms, we characterized a small conserved region that is sufficient for binding an AChET tetramer, the proline-rich attachment domain (PRAD). We show that the WAT domain alone is sufficient for association with the PRAD, and that it can attach foreign proteins (alkaline phosphatase, GFP) to a PRAD-containing construct with a glycophosphatidylinositol anchor (GPI), and thus anchor them to the cell surface. Furthermore, we show that isolated WAT domains, or proteins containing a WAT domain, can replace individual AChET subunits in PRAD-linked tetramers. This suggests that the four WAT domains interact with the PRAD in a similar manner. These quaternary interactions can form without intercatenary disulfide bonds. The common catalytic domains of AChE are not necessary for tetrameric assembly, although they may contribute to the stability of the tetramer.

Acetylcholinesterase↗

Effect of electromyogram-force relationships and method of gain estimation on the predictions of an electromyogram-driven model of spinal loading.

STUDY DESIGN: An experimental study of fatiguing isometric trunk extension was conducted to investigate the spinal loading estimated from an electromyogram-assisted biomechanical model. OBJECTIVE: To evaluate the sensitivity of the model outputs to two crucial assumptions: electromyogram-force relationship and method of gain estimation. SUMMARY OF BACKGROUND DATA: In the proposed electromyogram-assisted models of the trunk, the nature of the electromyogram-force relationship and the wide variation in reported muscle gains can result in a wide variation in estimates of spinal loading. Given the absence of any gold standard for validation of muscle forces, the delineation of confidence intervals for the estimated loads has become critical. METHODS: Ten subjects performed a fatiguing isometric trunk extension while the net muscular torque output and trunk muscular activity were measured. An electromyogram-assisted model was used to estimate the torque output and spinal loading. Linear and nonlinear erector spinae electromyogram-force relationships and three methods for gain estimation were investigated: constant gain determined from an initial maximum extension exertion, constant gain based on the fatiguing exertion, and a time-varying gain from the fatigue test. RESULTS: The predicted torque was not sensitive to the electromyogram-force relationship; the nonlinear model produced 10% lower estimates of peak spinal compression force and 14% higher estimates of peak anterior shear force. The gain determined from an initial calibration exertion underestimated the external torque and underpredicted the peak compression force by 20%, compared with gains calculated in the fatigue test. CONCLUSION: The nature of the electromyogram-force relationship and of the method for estimating the gain significantly affect the outcomes of an electromyogram-assisted model of spinal loading.

Adult↗

Standardized structure and modular design of a pharmacokinetic database.

BACKGROUND: The accumulated knowledge on drugs can be used for an individual drug dosage adjustment if it is placed at our disposal in an informatically structured form. THEORY AND METHODS: We have started building up a pharmacokinetic database aimed at adjusting drug dosages, in exemplary form, to patients with renal impairment. Parameters needed for the three dosage adjustment rules (Dettli, Kunin, Holford) and the most general concept of pharmacokinetics constituted the theoretical basis. TWO PROCESSES PERTAIN TO ALL DRUGS: Distribution and elimination. Total drug clearance and at least two parameters representing distribution and elimination processes are closely interdependent in mathematical terms (clearance = volume of distribution*rate of elimination). This relation yields the unifying concept that serves as a prerequisite for a structured recording of 30 assigned pharmacokinetic and pharmacodynamic parameters within an informatic database. SOLUTIONS AND RESULTS: The information is retrieved and referenced from 2383 original publications by means of a standardized input module. The complete database at present contains 15,397 records for 1573 drugs. A programmed meta-analytic algorithm is used to calculate the statistical measures for the central value and variance--as available--from the pooled values of primary records. The statistically standardized parameters are extracted for 6601 pharmacokinetic parameters, and placed at the users disposal with the output module. PRACTICAL UTILITY: Following meta-analysis, published pharmacokinetics can be used as statistical estimates of population parameters. The statistical estimates with variances permit an individual drug dosage adjustment by applying the Bayesian approach or neural networks.

Algorithms↗

Resource allocation during the rereading of scientific texts.

Two experiments examined how cognitive resources are allocated to comprehension processes across two readings of the same scientific texts. In Experiment 1, readers read and later reread texts describing scientific topics. The results indicated that across readings, readers decreased resources allocated to proposition assembly, increased resources allocated to text-level integration, and expended a similar amount of resources to lexical access. Subjects who reread the texts after a week delay showed a similar pattern, except that they did not show the increase for text-level integration. Experiment 2 revealed a similar pattern of results with a moving window procedure, except that there was a significant decrease in resources allocated to lexical access across exposures. This experiment also indicated that the rereading speedup was greatest at sentence boundaries, suggesting that the prior exposure enabled readers to immediately process each word. Overall, the results are consistent with the claim that readers allocate proportionally more available resources to text-level integration during rereading because proposition assembly, which enables text-level integration, can be completed with fewer resources.

Adult↗

The effect of lifting belt use on multijoint motion and load bearing during repetitive and asymmetric lifting.

The evaluation of the effect of lifting belts on multijoint coordinated lifting performance has been limited. Thirteen subjects participated in two experiments: (a) fatiguing repetitive sagittal lifting and (b) asymmetric lifting. Both experiments were performed with and without the use of a common flexible lifting belt to determine the effect of belt use on the trunk and lower extremity motion and load sharing. During both tests, the use of the belt was observed to restrict the sagittal trunk range of motion and velocity, while the hip motion and velocity increased. Although one of the risk factors for acquisition of low back pain may be reduced while wearing the belt, the results also demonstrate a need for greater study of the consequences on the risk of injury to the other joints. More laboratory experiments and prospective epidemiological studies are needed before a conclusive recommendation could be made in favor of using the belt as a valid preventive measure.

Adult↗

[Arterial hypertension and socioeconomic status in a representative population of French railway drivers].

UNLABELLED: High blood pressure (HDP) is known as a cardiovascular risk factor depending both on environmental and socio-economic factors. METHODS: From October 1993 to october 1994 a cross sectional study was carried out among 1,855 French railway drivers (FRD) representative of the 17,432 males FRD, aged 25 to 54 years. Age, weight, height, hip and waist, smoking, living area, type of train they drove (goods, suburban, TGV, inter-city trains), their grade (3 grades) were recorded. HBP corresponds to systolic blood pressure (BP) 160 mmHg or diastolic BP > or = 95 mmHg or to normal BP under antihypertensive medication. The analysis was carried out according to 2 age classes: 20-36/37-54 years. RESULTS: In our sample 8.5% of FRD suffered from HBP, 3.5% in the younger class, and 13.5% in the other one. Using univariate analysis, among the oldest, subjects with lower grades suffered more often from HBP (19%). Paris area was more often related to HBP for the 20-36 years (6.7%). This was the case for the oldest living in Paris area (19.7%), and the North East (15.2%). Subjects with central obesity (19.9 vs 6%), and hyperlipidemic FRD (20.9 vs 10.9%) were more often related to HBP in the 35-54 years group Whatever the type of train they drove no difference was found. In multivariate analysis, (stepwise logistic regression BMDP LR) independent HBP factors are: age OR 3.4 IC 1.9-5.9 (20-36 vs 37-54), central obesity OR 1.7 IC 1.1-2.6, tobacco consumption OR 2.1 IC 1.2-3.5 (smokers vs non smokers), ex-smokers: OR 2.3 IC 1.3-3.9 (Ex-smokers vs non smokers), living area (all regions vs South East in the Mediterranean border). Nevertheless, grades and type of train they drove were not independent factors. CONCLUSION: These results show the determining part played by environmental factors: age, central obesity, living area and tobacco consumption in the determinism of HBP in professional background: these factors can account for the difference observed in professional factor (grade).

Adult↗

Cloning and expression of acetylcholinesterase from Electrophorus. Splicing pattern of the 3' exons in vivo and in transfected mammalian cells.

We cloned and expressed a cDNA encoding acetylcholinesterase (AChE) of type T from Electrophorus electricus organs. When expressed in COS, HEK, and Chinese hamster ovary cells, the AChET subunits generated dimers and tetramers. The cells produced more activity at 27 than at 37 degrees C. The kinetic parameters of a recombinant enzyme, produced in the yeast Pichia pastoris, were close to those of the natural AChE. Analysis of genomic clones showed that the coding sequence is interrupted by an intron that does not exist in Torpedo and differs in its location from that observed in the mouse. This intron is preceded by a sequence encoding a non-conserved 29-amino acid peptide, which does not exist in Torpedo or mammalian AChEs. According to a three-dimensional model, this non-conserved peptide is located at the surface of the protein, opposite from the entry of the catalytic gorge; its deletion did not modify the catalytic parameters. Sequence analyses and expression of various constructs showed that the gene does not contain any H exon. We also found that splicing of transcripts in mammalian cells reveals cryptic donor sites in exons and acceptor sites in introns, which do not appear to be used in vivo.

Acetylcholinesterase↗

The effect of fatigue on multijoint kinematics and load sharing during a repetitive lifting test.

STUDY DESIGN: A repetitive lifting test in the sagittal plane was performed with a submaximal load at a maximal lifting rate to understand the effects of fatigue on kinematic and kinetic measures of performance. OBJECTIVES: To quantify the effect of fatigue during a highly repetitive lifting task, in terms of lifting force transmitted to the load, joint motion patterns, and internal joint load sharing. SUMMARY OF BACKGROUND DATA: Industrial surveillance and epidemiologic data suggest that repetitive lifting is a risk factor for low back pain. Previous studies examining the effect of fatigue have either been constrained to isolated trunk movement, or have not explored the internal load distribution and potential alteration in the loading patterns. METHODS: Sixteen healthy male subjects performed repetitive lifting in the sagittal plane with a load equal to 25% of their maximal lifting capacity, at a maximal lifting rate. Changes in lifting performance were determined from the power transferred to the box, joint kinematics, and joint kinetics. Data from three cycles at the start and end of the exercise were tested for the effect of fatigue using repeated-measures analysis of variance. RESULTS: Fatigue was documented by a reduction in average lifting force and hip and spine torque generation, whereas internal joint load sharing was relatively unchanged. The fatigue was associated with decreased knee and hip motion, and increased lumbar flexion. Decreased postural stability also was evident. CONCLUSIONS: The significant decrease in postural stability and force generation capability because of the repetitive lifting task indicated a higher risk of injury in the presence of unexpected perturbation. Multijoint coordinated lifting tasks provide a more realistic protocol to study neuromuscular fatigue.

Adult↗

Relationship between protein complotypes and DNA variant haplotypes: complotype-RFLP constellations (CRC).

From the study of 52 families and 15 homozygous typing cells, 234 MHC complement haplotypes were characterized for features in the DNA of the complotype region: C2/Sst I (2.75, 2.70, 2.65, and 2.40 kb), BF/Taq I (6.6 and 4.5 kb), C4 5'/Bgl II (15 and 4.5 kb), C4 5'/Taq I (7.0, 6.4, 6.0 and 5.4 kb) and C4 3'/Xba I/BamH I (11 and 4 + 7 kb) restriction fragment length polymorphisms (RFLP's), by the presence or absence of C4A, C4B, CYP21A and CYP21B genes and by duplications. Nineteen (of over 1000 theoretically possible) complotype-RFLP constellations (CRC's) were found. The 9 CRC's with two C4 and CYP21 genes were designated A through I. CRC's Bdup and Ddup were like B and D but had duplicated C4B-CYP21B genes. The remaining CRC's had deletions of C4 and/or CYP21 genes and were designated Bdel, Cdel and the like. Individual complement alleles and complotypes were nor randomly distributed among the CRC's. Some complotypes, such as SC01, SC02 and FIC30, were restricted to only 1 CRC; others, such as SC31, FC31, and SC30, were found in several CRC's. Some of the CRC's contained a single complotype, others contained several. Remarkably, there are about 30 CRC-specified complotypes with frequencies of .01 or higher and 14 of .02 or higher. A number of evolutionary origins of complement alleles and complotypes are suggested by the relationships among CRC's. Approximate normal frequencies of the undeleted CRC's were A = .27, B = .19, Bdup = .02, C = .17, D = .07, Ddup = .02, E = .06, F = .05, and G = .02. Thus, CRC's without deletions accounted for 88% of normal complotypes. Since the frequency of Bdel, with a deletion of C4A, was .12, 10 CRC's accounted for all observed normal caucasian MHC haplotypes.

Chromosome Mapping↗

Tyrosine phosphorylation of connexin 43 by v-Src is mediated by SH2 and SH3 domain interactions.

Reduction of gap junctional communication in v-src transformed cells is accompanied by tyrosine phosphorylation of the gap junction protein, connexin 43 (Cx43). Cx43 is phosphorylated on tyrosine by v-Src. The Src homology 3 (SH3) and Src homology 2 (SH2) domains of v-Src mediate interactions with substrate proteins. SH3 domains interact with proline-rich peptide motifs. SH2 domains associate with short amino acid sequences containing phosphotyrosine. We present evidence that the SH3 and SH2 domains of v-Src bind to proline-rich motifs and a phosphorylated tyrosine residue in the C-terminal tail of Cx43. Cx43 bound to the SH3 domain of v-Src, but not c-Src, in vitro. Tyrosine-phosphorylated Cx43 bound to the SH2 domain of v-Src in vitro. v-Src coprecipitated with Cx43 from v-src-transformed Rat-1 fibroblasts. Mutations in the SH3 and SH2 domains of v-Src, and in the proline-rich region or tyrosine 265 of Cx43, reduced interactions between v-Src and Cx43 in vivo. Tyrosine phosphorylation of Cx43 was dependent on the association of v-Src and Cx43. These results provide further evidence for the direct involvement of v-Src in tyrosine phosphorylation of Cx43 and inhibition of gap junctional communication in v-src-transformed cells.

Amino Acid Sequence↗

Skin carcinogenicity of condensed asphalt roofing fumes and their fractions following dermal application to mice.

Condensed roofing asphalt fumes, generated at 316 degrees C, were collected by cold trap condensation and fractionated by preparative high performance liquid chromatography. Chemical classes in each of the fractions (A-E) were identified by gas chromatography/mass spectroscopy. The fractions, various combinations of fractions, the raw and heated asphalt, the neat asphalt fume and the reconstituted asphalt were tested for carcinogenicity, and three fractions were tested for cocarcinogenicity and tumor promotion with benzo[a]pyrene (BaP). The skin application carcinogenesis bioassay was conducted by twice weekly application of test materials in 0.05 ml of acetone/cyclohexane (1:1) for 104 weeks to 40 groups of male C3H/HeJ mice (30/group). Fractions were applied at a mass in proportion to their amount in the neat asphalt fumes. In addition, the neat asphalt fume was tested on Sencar mice to determine if this strain was more susceptible to the carcinogenic effects of the fumes. Condensed neat asphalt fumes produced similar and statistically significant increased tumor yields of papillomas and carcinomas in both strains as compared to respective vehicle controls. Recombination of all fractions resulted in a tumor response similar to neat asphalt fumes. Among individual fractions, C was most potent, followed by B. The other single fractions were without significant tumorigenic activity. Combinations containing fractions B and C were most active among the mixtures that were assayed and no evidence of enhancement of tumorigenesis in the mixtures was found. No significant cocarcinogenic or tumor promoting activity was observed with fractions A, D, or E and BaP. Raw unheated asphalt produced a few tumors in C3H mice, but no tumors were seen when raw asphalt heated to 316 degrees C, with the fumes permitted to escape, was applied.

Animals↗

Spectral and temporal responses of trunk extensor electromyography to an isometric endurance test.

STUDY DESIGN: This study investigated the effect of trunk extensor muscle location on the spectral and temporal electromyographic activity of the muscles during a fatiguing isometric extension of the torso against gravity. OBJECTIVES: To determine the spectral responses of the trunk extensor muscles at more locations than have been studied previously, to determine if fatigue in the knee flexors limits this test, and to quantify the recruitment patterns of the trunk extensor muscles in a group of healthy subjects. SUMMARY OF BACKGROUND DATA: Isometric endurance tests appear to have more value than strength tests in predicting the occurrence of low back pain. Electromyographic activity of trunk extensor muscles during these tests may provide clues to the etiology of neuromuscular-based low back pain. Spectral electromyographic measures appear to be successful discriminators between low back pain patient and normal populations, although which muscles provide the best information is unclear. Likewise, the recruitment patterns of the trunk extensors during fatiguing isometric tasks is not well quantified. METHODS: Ten healthy men performed an isometric trunk endurance test. Surface electromyography was recorded from the erector spinae medially and laterally at vertebral levels of L1 and L3, medially at L5, and from the biceps femoris and gastrocnemius. Spectral parameters were calculated from the Fast Fourier Transform, and temporal parameters were calculated from the root mean square of the raw data. Linear regression was used to determine their responses as a function of time. RESULTS: There was a significant effect of vertebral level and medial-lateral location on the initial median frequency and linear slope of the median frequency regressions. No significant evidence of fatigue in the lower extremities was observed. For most subjects, the temporal response of the surface electromyography was parabolic (concave-down), peaking at 30-50% of the endurance time. CONCLUSION: Establishment of which muscle locations provide the best information and knowledge of the recruitment patterns are essential for the development of clinical diagnostic procedures and rehabilitation protocols.

Adult↗

In vivo characterization by means of digital cell image analysis of early-induced fractionated radiotherapy effects on the MXT mouse mammary tumor.

PURPOSE: To study the cell kinetics and chromatin modifications occurring in function of the fractionated irradiation administered to the MXT mouse mammary adenocarcinoma. METHODS AND MATERIALS: The MXT tumor cells were submitted to three fractions of a 4.8 Gy dose delivered at 24-h intervals. MXT tumor cells were collected by means of fine needle aspirations (between 5 and 10 samples were obtained after each irradiation) during treatment and submitted to the computer-assisted microscope analysis of Feulgen-stained specimens. Three groups of parameters has been described: i.e., the geometry of the nucleus, the nuclear DNA content, and the chromatin texture. Furthermore, cell cycle parameters were studied in the aim to know the distribution of the cells within the cell cycle. RESULTS: The mean values relating to geometric parameters (i.e., the nuclear area and its standard deviation) decreased during treatment. Variations in the nuclear DNA content appeared as being cyclical and could be explained in terms of the modifications in the distribution of the cells within the cell cycle. The quantitative analysis of the cell cycle parameters revealed that the percentage of S cells increased regularly after each irradiation. In contrast, the percentage of G2 cells decreased between each irradiation. The parameters describing nuclear texture showed regular variations between each irradiation. These variations consisted in two cycles constituted by a decrease in chromatin condensation, followed by an increase. CONCLUSIONS: The development of the geometric parameters indicates that fractionated radiotherapy leads to the emergence of a more homogeneous population. The effects of the radiotherapy on the distribution of the cells within the cell cycle could be explained through the phenomenon of repopulation and by the high degree of radiosensitivity of the G2 cells (decrease in the percentage of G2 cells). Last, the variations observed at chromatin pattern level could be explained through DNA repair processes.

Animals↗

Proximal tubular injury in Chinese herbs nephropathy: monitoring by neutral endopeptidase enzymuria.

Neutral endopeptidase (NEP) is a 94 kDa ectoenzyme of the proximal tubule brush border, physiologically released into the urine with apical membrane fragments. As proximal tubular atrophy was a histological hallmark of Chinese herbs nephropathy (CHN), this study firstly determined renal excretion of NEP in healthy control subjects (N = 31), in patients with CHN (N = 26) and in women having consumed Chinese herbs and whose renal function was normal but running the risk of developing CHN (N = 27). Another patient group consisted of female patients with glomerular diseases (N = 12). At the same time, measurements of urinary microproteins (Clara cell protein, retinol binding protein, beta 2-microglobulin and alpha 1-microglobulin) were performed, as indicators of tubular dysfunction. Cell damage was estimated by the excretion of N-acetyl-beta-D-glucosaminidase (NAG). In the control group, the physiological NEP enzymuria was 43.1 micrograms/24 hr (geometric mean). In CHN patients, levels of urinary NEP were significantly decreased in those with moderate renal failure (26.7 micrograms/24 hr; N = 21; P < 0.05) and almost abolished in end-stage renal failure patients (4.35 micrograms/24 hr; N = 5; P < 0.05). In patients at risk as well as in patients with glomerular diseases, urinary NEP levels were not statistically different from those observed in control subjects (40.68 micrograms/24 hr and 48.5 micrograms/24 hr, respectively). Several degrees of tubular dysfunction and injury were noted in patients groups, as attested by increased urinary microproteins and NAG excretions. Considering the data from control and CHN patients, NEP enzymuria positively correlated with individual creatinine clearance values (r = 0.76; P = 0.0001) and negatively correlated with urinary microproteins levels (r = -0.55; P = 0.00001). Finally, NEP was regularly quantitated in the urine of 6 CHN patients for a period ranging from six months to two years and in 19 patients at risk during two years, respectively. In the first group, renal function progressively deteriorated in 3 patients, leading them to renal replacement therapy after 38 to 115 weeks. Stable parameters were observed in the remaining 3 patients. A direct correlation between creatinine clearance and NEP excretion was found longitudinally in each case. In the second group, no significant change of urinary NEP levels was observed (45.9 micrograms/24 hr), in parallel with stable renal function. Taken together, these results indicate that, in CHN patients, NEP enzymuria provides a rapid and noninvasive determination of the degree of structural impairment affecting the proximal tubular population and further reflecting the severity of the renal disease. The interest of this urinary marker in monitoring the progression of other tubulointerstitial diseases remains to be assessed.

Adult↗