The distribution and metabolism of ACTH and the dynamics of the adrenal cortical response to this tropic hormone were characterized
in the rat, through mathematical models involving data derived from experiments, where plasma corticosterone concentrations
were measured following both single injections and infusions of ACTH. The models, which incorporate a previously established
model of the dynamics of plasma corticosterone, were statistically validated. The simulated dynamics of the different processes
linking ACTH secretion by the adenohypophysis to corticosterone secretion by the adrenal cortex include: (1) a variable MCR
for plasma ACTH, modeled as the sum of a constant and a saturable degradation process; (2) the ability of the adrenal gland
to secrete at a maximal rate aven after the plasma ACTH concentration has become negligible, modeled as the accumulation of
an intermediary productZ directly controlled by the plasma ACTH concentration; (3) a saturable secretion with a small time constant and which, for
single injections, always starts in the same fashion, modeled as a “synthesis process” whose input is a saturable function
ofZ; (4) an immediate fall of the plasma corticosterone concentration at the end of the ACTH infusions, modeled as a “release
process” also controlled byZ.
Supported by grants from the Medical Research Council of Canada (MT-1205, MT-1555, and MA-4970), and from INSERM, France (CRL-76-5-020-4). 相似文献
Using Southern blot analysis of DNAs from human×rodent cell hybrids, we have mapped the CD23 leukocyte antigen gene (FCE2) to human chromosome 19. 相似文献
DNA methylation plays an important part in the regulation of gene expression. Alterations in DNA methylation in tumours have
been reported and have been used to generate hypotheses about mutagenesis and silencing of tumour suppressor genes. However,
the underlying mechanism is still poorly understood, and conflicting data on the levels of overexpression of 5′-cytosine DNA
methyltransferase in sporadic colon carcinoma have been published. We used a competitive RT-PCR assay for quantification of
mRNA of 5′-cytosine DNA methyltransferase in colon biopsies obtained from patients with hereditary colon carcinoma syndromes
and compared the results with those obtained in a control group. No significant difference was found between the flat mucosa
of FAP patients and the mucosa of the control group. In FAP and HNPCC patients, the 5′-cytosine DNA methyltransferase mRNA
levels of adenomas were significantly higher (P<0.05) than of flat mucosa in the same group, but both showed great variability from patient to patient. Our findings suggest
that the mRNA levels of methyltransferase cannot be used as predictive marker for screening in families affected by hereditary
colon carcinoma.
Received: 20 July 1998 / Accepted: 21 September 1998 相似文献
Aminoglycosides are bactericidial antibiotics with a serum concentration-dependent activity. They are mainly eliminated by the kidneys and the main difficulty arising in clinical use is their uptake by the renal cortex which leads to nephrotoxicity. An ototoxicity is also reported. We propose a PK/PD modelling of aminoglycoside nephrotoxicity which unifies more fourty years of physiological knowledge. This deterministic model successively describes the pharmacokinetics of aminoglycosides, their storage into renal cortex, their effect on renal cells, their consequences on the renal function through tubuloglomerular feedback and the changes in the serum concentrations of creatinine that is considered as a toxicity marker. The simulation of the model displays the leading effect of the shape and daily-time of administration schedule on the search for minimizing toxicity. 相似文献
CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell activation and found that T cell receptor (TCR) stimulation induced a physical association of CARMA1 with the TCR and Bcl10. We found that CARMA1 was constitutively associated with lipid rafts, whereas cytoplasmic Bcl10 translocated into lipid rafts upon TCR engagement. A CARMA1 mutant, defective for Bcl10 binding, had a dominant-negative (DN) effect on TCR-induced NF-kappa B activation and IL-2 production and on the c-Jun NH(2)-terminal kinase (Jnk) pathway when the TCR was coengaged with CD28. Together, our data show that CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation and CD28 costimulation-dependent Jnk activation. 相似文献
In order to study the influence of the nature of the moiety bearing a tetrathiafulvalenyl group in the polymers upon the microlithographic properties of resists, poly(p-chloromethylstyrene)s and poly(styrene-co-p-chloromethylstyrene)s containing the 4-tetrathiafulvalenylphenoxymethyl group with a variety of controlled molecular weights and molecular weight distributions were studied. The copolymers were all prepared by reaction of poly(4-vinylbenzyl chloride) with potassium 4-tetrathiafulvalenylphenolate ( 3 ). Without exception, the resulting poly[p-chloromethylstyrene-co-p-(tetrathiafulvalenylphenoxymethyl)styrene]s are highly insoluble. However, by reaction of potassium 4-tetrathiafulvalenylphenolate with poly(styrene-co-p-chloromethylstyrene) soluble copolymers could be prepared. 相似文献
Lipoprotein lipase (LPL) plays a major role in triglyceride (TG)-rich lipoprotein catabolism. A mutation at codon 207 (P207L) in the exon 5 of the LPL gene has been associated with 50% reduction in postheparin plasma LPL activity and significant increase in plasma TG levels in heterozygous individuals with low HDL. However, heterogeneity in fasting TG concentrations among these carriers suggests that other factors may be involved in the expression of this hypertriglyceridemic state. Indeed, previous studies have shown that the rare S2 allele of the APOC3 Sst I polymorphism was associated with higher concentrations of TG levels in noncarriers of LPL defect. Therefore, we investigated the association of the APOC3 Sst I variant on fasting lipoprotein-lipid levels in a sample of 35 heterozygous men bearing the LPL P207L mutation. Genetic association analyses were performed using the two-genotype groups S1/S1 and S1/S2. The genotype S1/S2 group was characterized by greater plasma cholesterol (plasma-C, P=0.02), plasma-TG (P=0.04), very low-density lipoproteins (VLDL)-C (P=0.004), VLDL-TG (P=0.01), VLDL-apolipoprotein B (apoB) (P=0.001) levels and cholesterol/HDL-C ratio (P=0.008), as well as lower VLDL-TG/VLDL-apoB ratio compared to the S1/S1 genotype group. These results support an exacerbating effect of the APOC3 Sst I single-nucleotide polymorphism on fasting TG levels since a large number of smaller VLDL particles are observed in LPL-deficient men bearing the APOC3 S2 allele. 相似文献
1. The production of heat and (internal) work and the changes in the amount of phosphocreatine (PCr), ATP, inorganic phosphate (Pi) and sometimes lactate have been measured from moment to moment during and after tetanic isometric contractions of isolated frog muscles at 0° C.
2. Heat production was measured by thermopiles and a novel apparatus was employed for freezing the muscles rapidly at a chosen instant so as to halt the chemical processes before analysis.
3. Using unpoisoned muscles in oxygen, it was shown that neither oxidative recovery processes nor glycolytic ones led to appreciable restitution of PCr or ATP during 15 sec of contraction. However, clear signs of recovery processes could be seen within a minute. In our preparations artificial `ageing' by storage at low temperature did not interfere with the capacity for glycolysis.
4. Our clearest result was that the break-down of PCr was not nearly large enough to account for the rapid heat production during the first few sec of contraction. By the end of a 15 sec tetanus as much as 10 mcal/g remained unaccounted for.
5. The source of this heat is not clear. At no time is there any sign of net break-down of ATP; indeed there appears to be a slight increase of ATP in the stimulated muscle.
6. Break-down of PCr continues both during relaxation and during the minute following, while the muscle is at rest. Thus during contraction there is heat production without PCr break-down, while subsequently there is PCr break-down without heat production.
The compact → coil conformational transition of hydrophilic-hydrophobic copolymers derived from poly(methacrylic acid) was studied by UV Spectroscopy. Two copolymers were used in this study: a Poly(N-methacryloylalanine-co-N-phenylmethacrylamide) (P50) and a poly(methacrylic acid-co-benzyl methacrylate) (S25). Both samples exhibit hypochromism in the absorption band of the aromatic chromophore when they are under the compact conformation: 7% and 30% hypochromism for P50 and S25, respectively. This difference is explained by differences in the hydrophobic side chain-side chain interactions between the aromatic residues. Increasing the temperature was found to increase strongly the hypochromism of S25 and to have little effect on P50. 相似文献