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PubMed1994

Microtubule centers and the interphase microtubule cytoskeleton in amoebae of the cellular slime molds (Mycetozoans) Acytostelium leptosomum and Protostelium mycophaga.

We investigated the microtubule (MT) cytoskeleton and microtubule centers (MTC) in undifferentiated amoebae by indirect immunofluorescence with six monoclonal antitubulin antibodies, and by transmission electron microscopy and immunogold ultracytochemistry. Interphase amoebae of both species contain a distinct cytoplasmic complex of MTs, which is more elaborate in Protostelium mycophaga. In Acytostelium leptosomum amoebae a single MTC is attached to each interphase nucleus at its pointed end, as in the other dictyostelid cellular slime molds Dictyostelium discoideum and Polysphondylium violaceum. Ultrastructurally, MTCs of A. leptosomum also resemble those of these two species: They consist of an electron-opaque core shaped like a stout rod, which is embedded, together with nodules, in a fuzzy matrix. The nodules are the points of origin of the MTs. In most amoebae of P. mycophaga there are two MTCs on opposite sides of and close to the nucleus, but many amoebae also contain a variable number of MTCs that are remote from the nucleus. Nucleus-associated and "remote" MTCs are structurally identical. They consist of a ring-shaped core with inner and outer diameters of ca. 130 nm and 340 nm. A plug sits in the ring, and satellites are connected to the core by fine fibrils. The satellites are the points of origin of MTs. New MTCs are apparently formed during mitosis, the parent MTC probably serving as a template for the genesis of a new ring. The results support the notion that phylogenetically related organisms have similarly constructed MTCs and that these are dissimilar in less closely related organisms.

Antibodies, Monoclonal↗
PubMed2002

Very early detection of RET proto-oncogene mutation is crucial for preventive thyroidectomy in multiple endocrine neoplasia type 2 children: presence of C-cell malignant disease in asymptomatic carriers.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the RET proto-oncogene, and is responsible for the development of endocrine neoplasia. Its prognosis is dependent on the appearance and spread of medullary thyroid carcinoma (MTC). Relatives at risk can be identified before clinical or biochemical signs of the disease become evident. METHODS: Twenty-one families with MEN 2 (16 families with MEN 2A and 5 families with MEN 2B) were studied. Peripheral blood DNA was amplified by polymerase chain reaction. DNA sequence or restriction enzyme analysis was performed to detect mutations of RET proto-oncogene exons 10, 11, and 16. Molecular analysis was carried out in all index patients as well as in 98 relatives of MEN 2A patients (60 juveniles, ages 6 months to 21 years, and 38 adults, ages 22 to 81 years) and in 13 relatives (6 juveniles ages 10 to 21 years, and 7 adults ages 41 to 66 years) from MEN 2B families. RESULTS: Molecular studies showed a mutation at codon 634, exon 11 in all MEN 2A patients. All MEN 2B patients showed an ATG to ACG (Met918Thr) mutation. In MEN 2A families, 42 out of 98 relatives were affected. Total thyroidectomy was performed in 18 juvenile carriers ages 17 months to 21 years. Histopathologic studies of the glands revealed parafollicular cell (C-cell) hyperplasia in all of these carriers, medullary thyroid carcinoma in 15 carriers, and only one carrier with lymph node metastases. CONCLUSIONS: The consistent finding of C-cell disease in all the juvenile carriers who underwent preventive thyroidectomy emphasizes the relevance of early screening in children at risk of developing MTC. The presence of MTC in the specimen of prophylactic thyroidectomy from a 17 month old girl highlights the importance of thyroidectomy as soon as the molecular diagnosis is confirmed.

Adolescent↗
PubMed2006

Cytoarchitectonic subdivisions of the dorsolateral frontal cortex of the marmoset monkey (Callithrix jacchus), and their projections to dorsal visual areas.

We describe the organization of the dorsolateral frontal areas in marmoset monkeys using a combination of architectural methods (Nissl, cytochrome oxidase, and myelin stains) and injections of fluorescent tracers in extrastriate areas (the second visual area [V2], the dorsomedial and dorsoanterior areas [DM, DA], the middle temporal area and middle temporal crescent [MT, MTc], and the posterior parietal cortex [area 7]). Cytoarchitectural field 8 comprises three subdivisions: 8Av, 8Ad, and 8B. The ventrolateral subdivision, 8Av, forms the principal source of frontal projections to the "dorsal stream," having connections with each of the injected visual areas. The cytoarchitectural characteristics of 8Av suggest that this subdivision corresponds to the marmoset's frontal eye field. The intermediate subdivision of area 8 (8Ad) has efferent projections to area 7, while the dorsomedial subdivision (8B) has few or no connections with extrastriate cortex. Area 46, located rostrolateral to area 8Av, has substantial connections with the medial extrastriate areas (DM, DA, and area 7) and with MT, while the cortex lateral to 8Av (area 12/45) projects primarily to MT and to the MTc. The rostromedial prefrontal (area 9) and frontopolar (area 10) regions have very few extrastriate projections. Finally, cells in dorsal area 6 (6d) have sparse projections to DM, MT, and the MTc, as well as strong projections to DA and to area 7. These results illuminate aspects of the evolutionary development of the primate frontal cortex, and serve as a basis for further research into cognitive functions using a marmoset model.

Amidines↗
PubMed2003

Novel intronic polymorphisms in the RET proto-oncogene and their association with Hirschsprung disease.

Germline mutations of the RET proto-oncogene have been found in familial and sporadic forms of Hirschsprung disease (HSCR), but also in the autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN2) syndromes, which comprise the medullary thyroid carcinoma (MTC) as an obligatory feature. Besides mutations various polymorphisms of the RET proto-oncogene are associated with the HSCR. In this study, we have characterized seven intronic RET polymorphisms (IVS2+9G>A, IVS4+48A>G, IVS12+47C>T, IVS14-24G>A, IVS19+47T>C, IVS20+96C>T, 3'UTR+124A>G) and investigated these variants by DNA sequencing in populations of 76 HSCR patients and 40 sporadic MTC patients as well as in a control population. Variants of four of these seven polymorphisms have a strong association with the HSCR phenotype. In contrast, none of the investigated polymorphisms show a significant difference in the genotype distribution and the allele frequencies in patients with sporadic MTC when compared to controls. These findings support the hypothesis that specific RET haplotypes cause or modify the HSCR phenotype.

Female↗
PubMed1991

Expression of cholecystokinin forms by medullary thyroid cancer.

We have studied the production and release of cholecystokinin (CCK) forms by rat medullary thyroid cancer (MTC) in vivo. MTC cells were inoculated s.c. into 8 Wag-Rij rats. One month later, after i.v. injection of calcium plasma levels of CCK, calcitonin and tissue contents of gastrin and calcitonin were determined by radioimmunoassay (RIA), immunocytochemistry, and high-pressure liquid chromatography (HPLC). The tumors were passed 4 times to 8 rats in 1-month intervals fasting levels of CCK in control rats were unaffected by calcium stimulation, and in tumor-bearing rats, plasma CCK was elevated in 3 out of 4 passages, falling to normal levels at the end of passage 4. Hypercalcemia had no effect on plasma levels of CCK in tumor-bearing rats, but did stimulate the release of calcitonin in both control and some tumor-bearing rats in later passages. CCK-8 sulfate was found in all 4 tumor passages but not CCK-33/39. We conclude that rat MTC synthesizes and releases CCK-8, but unlike calcitonin, release of CCK appears unresponsive to calcium stimulation.

Animals↗
PubMed2003

T2 quantitation of articular cartilage at 1.5 T.

PURPOSE: To evaluate sources of error when using a multiecho sequence for quantitative T2 mapping of articular cartilage at 1.5 T. MATERIALS AND METHODS: Phantom measurements were used to assess the contribution of stimulated echoes to inaccuracy of T2 measurements in cartilage using a multiecho sequence. Five volunteer studies compared in vivo single-echo spin echo results to multiecho, single-slice and multiecho, multislice acquisitions for assessment of both the stimulated echo and magnetization transfer contrast (MTC) contributions to T2 measurement inaccuracy. RESULTS: Phantom experiments demonstrated that substantial inaccuracy (10%-13% longer T2 values) is introduced from stimulated echoes with a multiecho sequence with slice-selective refocusing pulses. The in vivo volunteer studies also demonstrated increases in measured T2 by up to 48% with a multiecho sequence. Use of the multiecho sequence in the multislice mode resulted in T2 values closer to the single-echo standards for the volunteer studies. However, this apparent increased accuracy should be regarded as circumstantial, as it only occurs because the error due to MTC has the opposite sign compared to the error due to the stimulated echo contribution. CONCLUSION: Use of a multiecho, multislice sequence for cartilage T2 measurements should be undertaken with the caution that substantial inaccuracy is introduced from stimulated echoes and MTC.

Adult↗
PubMed1995

Multi-slice MRI of rat brain perfusion during amphetamine stimulation using arterial spin labeling.

When a single coil is used to measure perfusion by arterial spin labeling, saturation of macromolecular protons occurs during the labeling period. Induced magnetization transfer contrast (MTC) effects decrease tissue water signal intensity, reducing the sensitivity of the technique. In addition, MTC effects must be properly accounted for in acquiring a control image. This forces the image to a single slice centered between the labeling plane and the control plane. In this work, a two-coil system is presented as a way to avoid saturation of macromolecular spins during arterial spin labeling. The system consists of one small surface coil for labeling the arterial water spins, and a head coil for MRI, actively decoupled from the labeling coil by using PIN diodes. It is shown that no signal loss occurs due to MTC effects when the two-coil system is used for MRI of rat brain perfusion, enabling three-dimensional perfusion imaging. Using the two-coil system, a multi-slice MRI sequence was used to study the regional effects of amphetamine on brain perfusion. Amphetamine causes significant increases in perfusion in many areas of the brain including the cortex, cingulate, and caudate putamen, in agreement with previous results using deoxyglucose uptake to monitor brain activation.

Amphetamine↗
PubMed1997

Magnetization transfer imaging in vivo of the rat brain at 4.7 T: interpretation using a binary spin-bath model with a superLorentzian lineshape.

Proton magnetization transfer contrast (MTC) imaging, using continuous wave off-resonance irradiation, was performed on the rat brain in vivo at 4.7 Tesla. The observed MTC was studied in three different brain regions: the corpus callosum, the basal ganglia, and the temporal lobe. By systematically varying the offset frequency and the amplitude of the RF irradiation, the observed signal intensities for each region of interest were modeled using a system including free water and a pool of protons with restricted motions (R. M. Henkelman, X. Huang, Q. Xiang, G. J. Stanisz, SD Swanson, M. J. Bronskill, Magn. Res. Med. 29, 759 (1993)). Most of the relaxation parameters of both proton pools remained fairly constant for the three regions of interest, with a T2 value of about 9 micros for the immobilized protons, whereas the rate of exchange increased significantly from the temporal lobe to the corpus callosum. The optimal acquisition parameters for the improved MTC under steady-state saturation were found to be 2-10 kHz offset frequency and 500-800 Hz RF irradiation amplitude. Conversely, an irradiation amplitude of 3 kHz at an offset frequency of 12 kHz is required to minimize the direct effect of off-resonance irradiation. Such an approach could be extended to human brain imaging with the aim of characterizing tissue-specific disease.

Animals↗
PubMed2004

Combination of direct and indirect evidence in mixed treatment comparisons.

Mixed treatment comparison (MTC) meta-analysis is a generalization of standard pairwise meta-analysis for A vs B trials, to data structures that include, for example, A vs B, B vs C, and A vs C trials. There are two roles for MTC: one is to strengthen inference concerning the relative efficacy of two treatments, by including both 'direct' and 'indirect' comparisons. The other is to facilitate simultaneous inference regarding all treatments, in order for example to select the best treatment. In this paper, we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS. These are multivariate random effects models that allow for variation in true treatment effects across trials. We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models. We also compare models with fixed (unconstrained) baseline study effects with models with random baselines drawn from a common distribution. These models are applied to an illustrative data set and posterior parameter distributions are compared. We discuss model critique and model selection, illustrating the role of Bayesian deviance analysis, and node-based model criticism. The assumptions underlying the MTC models and their parameterization are also discussed.

Humans↗
PubMed1992

Serotonergic signalling between thyroid cells: protein kinase C and 5-HT2 receptors in the secretion and action of serotonin.

Parafollicular (PF) cells of the thyroid gland are neural crest derivatives, which costore the neurotransmitter, 5-hydroxytryptamine (5-HT) with calcitonin. PF cells are located adjacent to follicular (F) cells within the basement membrane of thyroid follicles. It has been proposed that 5-HT serves an intercellular signalling function in the thyroid and that F cells are its target. This proposal was tested by using cell lines derived from PF (medullary thyroid carcinoma [MTC]) and F (FRTL-5) cells to study the mechanisms that mediate the secretion and action of 5-HT. Secretion of 5-HT by MTC cells was evoked by thyroid stimulating hormone, thyrotropin (TSH), elevated extracellular calcium (increases [Ca2+]e), or by agents that increase intracellular cAMP (increases [cAMP]i). When protein kinase C (PKC) was down-regulated by prolonged treatment of MTC cells with phorbol 12-myristate 13-acetate (PMA), or PKC was inhibited by staurosporin, the TSH- or PMA-evoked secretion of 5-HT was blocked; however, interference with PKC function did not affect 5-HT secretion evoked by increases [Ca2+]e or increases [cAMP]i. In the putative targets, FRTL-5 cells, 5-HT increased the turnover of phosphoinositides (PI), cytosolic calcium (increases [Ca2+]i), increases [cAMP]i, and biphasically modified the effect of TSH on cAMP. All of these 5-HT effects were inhibited by 5-HT2 receptor antagonists (spiperone and ketanserin) and by pertussis toxin (PTx), suggesting that the actions of 5-HT are mediated by 5-HT2 receptors, which are coupled to a G protein. This suggestion was supported by the following additional observations: FRTL-5 membranes bound the 5-HT2 agonist, [125I]2,5-dimethoxy-4-iodophenylisopropylamine ([125I]-DOI), and anti-idiotypic antibodies, which recognize 5-HT2 receptors. [125I]-DOI binding was inhibited by guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) and the antibodies were displaced by spiperone. Data are consistent with the hypothesis that 5-HT serves as a PF to F cell messenger.

Alkaloids↗
PubMed1998

Suppression of ruffling by the EGF receptor in chemotactic cells.

To clarify the relationship between ruffling and lamellipod extension in growth factor-stimulated chemotactic responses, we utilized cell lines derived from the rat 13762 NF mammary adenocarcinoma. Nonmetastatic MTC cells expressing the human EGF receptor (termed MTC HER cells) demonstrated chemotactic responses to TGF-alpha, an EGF receptor ligand typically present in mammary tissue. In microchemotaxis chambers, peak chemotactic responses occurred in response to 5 nM TGF-alpha. MTC HER cells showed dramatic ruffling edges in the absence of external stimuli, and addition of 5 nM TGF-alpha led to a transient reduction in ruffling concomitant with lamellipod extension. Lamellipod extension correlated with an overall increase in actin polymerization. These responses were blocked by the PI 3 kinase inhibitor wortmannin but not by the MAP kinase inhibitors PD98059 and SB203580. We conclude that the initial chemotactic response to TGF-alpha involves lamellipod extension and that ruffling reflects a dynamic turnover of lamellipodia that is arrested during lamellipod extension. By regulating the dissolution of ruffles and extension of lamellipods, a chemotactic response can be achieved, which may contribute to the metastatic process.

Actins↗
PubMed2001

Rapid and specific detection of the Mycobacterium tuberculosis complex using fluorogenic probes andreal-time PCR.

A rapid and sensitive strategy for the specific identification of Mycobacterium tuberculosis (TB) was designed and evaluated using crude mycobacterial lysates. The speed of real-time polymerase chain reaction (PCR) was combined with the sensitivity of fluorogenic probes to confirm the presence of mycobacteria as well as specifically identify the presence of members of the mycobacteria tuberculosis complex (MTC) in a single-tube assay. Oligonucleotides were designed to amplify the internal transcribed spacer (ITS) from several mycobacterial species. Specific fluorogenic probes were included in the PCR reaction for the identification of TB as well as Mycobacterium bovia and Mycobacterium africanum in bacterial lysates. The combination of TB-specific fluorogenic probes with real-time PCR formed an approach determined to be fast (less than 40 min), sensitive (less than 800 copies of DNA) and reliable for the specific detection of the MTC. Our data demonstrate the use of real-time PCR and fluorogenic probes in a rapid and sensitive assay to distinguish members of the MTC from other mycobacterial species.

DNA Primers↗
PubMedDate not supplied

Chromosome and DNA analyses of rat 13762NF mammary adenocarcinoma cell lines and clones of different metastatic potentials.

Chromosome morphologies revealed by Giemsa-banded karyotypes and chromosome numbers were compared between parental tumor-, lymph node- and lung metastasis-derived rat 13762NF mammary adenocarcinoma cell lines and clones having different spontaneous metastatic potentials. Although chromosome numbers in the cell lines and clones generally correlated with DNA content by flow cytometry, ploidy did not correlate with spontaneous metastatic potentials. Chromosome number and DNA content drifted during prolonged in vitro growth in each of the cell lines and clones. Common chromosome rearrangements were found, confirming a common origin for all the cell lines and clones, and the frequency and appearance of the individual marker chromosomes fluctuated during in vitro growth. Karyotypic analyses revealed that the markers coinciding with phenotypic drift in spontaneous metastatic potential and other biological properties of parental tumor-derived clones MTC and MTF7 and lung metastasis-derived clone MTLn3 involved chromosomes 3, 4, 5, 6, and 8. Clone MTC exhibited a shift in several markers and an increase in metastatic potential at passage T20, while clone MTF7 displayed a lesser spontaneous metastatic potential at high passage (T34) concomitant with an increase in the frequency of certain marker chromosomes. Lung metastasis-derived clone MTLn3 also exhibited a shift in some marker chromosomes, colonization preference and metastatic potential to lung and lymph nodes at high tissue culture passages. The changes in marker chromosomes during in vitro passage of clones MTC and MTLn3 suggested the presence of at least two cell subpopulations which could be responsible for the observed shift in spontaneous metastatic properties. Karyotypic features of the 13762NF cell lines and clones indicate that subtle cytogenetic changes, in contrast to gross chromosomal abnormalities, may be more important in determining metastatic phenotype.

Animals↗
PubMed1993

Utility of thallium-201 and iodine-123 metaiodobenzylguanidine in the scintigraphic detection of neuroendocrine neoplasia.

Metaiodobenzylguanidine (MIBG) is a specific marker for neuroendocrine tumours, such as phaeochromocytoma, neuroblastoma, medullary thyroid cancer (MTC) and paraganglioma, but it suffers in some cases (especially in MTC) from a lack of sensitivity. Thallium is a well-known marker of cellularity with a great sensitivity and a lack of specificity. In order to determine whether the association of these two markers is able to improve the detection of neuroendocrine lesions, 137 scintigraphic examinations using MIBG and thallium were performed in 101 patients referred for suspicion or follow-up of neuroendocrine tumours. Thallium chloride was first injected (1 MBq/kg), images being acquired about 20 min after injection; 123I-MIBG (4 MBq/kg) was then injected and images acquired 5 and 24 h later. In patients with phaeochromocytoma or neuroblastoma, thallium scintigraphy appeared of little help since no tumoural site was discovered by thallium accumulation alone. In contrast, thallium examination seemed of interest in the detection of paraganglioma and MTC, the association of the two radiopharmaceuticals increasing the number of detected sites.

3-Iodobenzylguanidine↗
PubMed1992

[Trans-sternal cervico-mediastinal primary tumor resection and lymphadenectomy in thyroid gland cancer].

Thyroid carcinoma may invade the mediastinum by direct extension of the primary tumor or metastases to the paratracheal or retroclavicular-parajugular lymph nodes. From 1975 to 1991 in 47 out of 622 thyroid cancer patients (7.6%) [14 papillary (PTC), 5 follicular (FTC), 16 medullary (MTC) and 12 undifferentiated carcinoma (UTC)] transsternal tumor resection has been performed. Four patients (UTC three, MTC one) deceased 7, 8, 35, and 41 days after resection of the primary tumor due to cardiac or tumor disease, and in one patient because of acute arteriotracheal haemorrhage after external irradiation; no patient deceased after transsternal resection as a result of cervicomediastinal lymphadenectomy. At the time of primary operation 80% of patients showed an advanced tumor stage (greater than pT3). In 34% of patients (PTC 64%, FTC 40%, MTC 13%, UTC 25%) no tumor recurrence was observed neither by imaging nor by biochemical methods. In 18 patients a transsternal microdissection of all four cervicomediastinal lymph node compartments has been performed. Histological analyses of excised and tumor involved lymph nodes revealed in 9 patients unilateral cervical and mediastinal and in 9 patients bilateral cervical and mediastinal lymph node metastases. In the case of unilateral cervicomediastinal lymph node metastases 2 out of 2 patients with papillary and 2 out of 6 patients with medullary thyroid carcinoma could be cured surgically. In the case of bilateral cervicomediastinal lymph node metastases 3 out of 4 patients with papillary thyroid carcinoma, but no other thyroid cancer patient were free of disease. In conclusion, main indications for transsternal cervicomediastinal resection in thyroid carcinoma are (1) primary tumors extending to the upper mediastinum, but without lymph node metastases, and (2) thyroid carcinomas with unilateral cervicomediastinal lymph node metastases. In the case of bilateral cervicomediastinal lymph node metastases probable only papillary thyroid carcinomas are supposed to be curable by transsternal multicompartmentectomy.

Adenocarcinoma↗
PubMed1986

Survival of rat mammary tumor cell clones and DNA strand damage following adriamycin treatment.

Tumor cell subpopulations have been shown to be heterogeneous in a number of phenotypic characteristics, including responses to cytotoxic drugs. This phenotypic heterogeneity has been used here to study mechanisms associated with Adriamycin (doxorubicin HCl)-induced cytotoxicity. Clonogenic survival and alkaline elution methods were employed to examine the response of two tumor cell subpopulations to Adriamycin. The cells were derived from a primary 13762NF rat mammary adenocarcinoma (clone MTC) and a lung metastasis in the same animal (clone MTLn3). The MTC cells were significantly more resistant to Adriamycin than were the MTLn3 cells; the dose effective in reducing cell survival by 50% was 10-fold higher. Protein-associated DNA strand breakage assayed by alkaline elution was dose-dependent in both clones, and MTC cells were again more resistant to break induction than were MTLn3. These results showed that clonal tumor subpopulations isolated from a primary tumor and its metastases possessed different intrinsic survival responses to Adriamycin treatment in vitro and that this survival response correlated with Adriamycin-induced production of protein-associated DNA single-strand breaks.

Animals↗
PubMed1980

Defective excision repair in a mutant of Micrococcus radiodurans hypermutable by some monofunctional alkylating agents.

The lethal and mutagenic effects of methyl methanesulphonate (MMS), ethyl methanesulphonate (EMS), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) can be dissociated in a mitomycin C (MTC)-sensitive mutant, strain 302, of Micrococcus radiodurans. As regards lethality 302 is extremely sensitive, compared with the wild type, to MTC and decarbamoyl MTC (DCMTC), slightly sensitive to EMS, MNNG, nitrous acid, 7-bromomethylbenz[alpha]anthracene (BrMBA), and N-acetoxy-N-2-acetylaminofluorene (AAAF), and resistant to MMS, hydroxylamine, and ICR 191G. As regards mutability it is, compared to the wild type, very sensitive to MMS, EMS, and MNNG, and slightly sensitive to hydroxylamine and nitrous acid but not to any other agent examined. Alkaline sucrose gradient studies indicate the 302 does not incise DNA containing BrMBA adducts, although it does incise DNA damaged by AAAF but probably not to the same extent as wild type. We put forward the hypothesis that the hypermutability of 302 is due to the non-removal of bases or nucleotides, modified in exocyclic positions, which have altered base-pairing capabilities, while lethality results from the non-removal of bases or nucleotides, also modified in exocyclic positions, which no longer form hydrogen-bonded base pairs.

DNA Repair↗
PubMed1996

Changes in renal blood flow measured by radionuclide angiography following exhausting exercise in humans.

We measured renal blood flow (RBF) repeatedly in six male volunteers following exhausting cycling exercise using radionuclide angiography (RA) with technetium 99 m phytate (99 mTc-phytate), which is a nondiffusible radio-active tracer for kidney imaging and which is taken up quickly by the liver after injection into the circulation. The relationships between changes in RBF and creatinine clearance (Ccr), urine volume (UV) and plasma hormone involved in the regulation of renal function were also investigated. A bolus of 99 mTc-phytate (92.5 MBq.ml-1) was injected into the brachial vein via a catheter, while each subject was maintained in a supine position with his back to a scinticamera, which was connected to a computer for data processing. The pool transit time (PTT) was calculated from the time-concentration flow curve in the left kidney following injection of the bolus. The PTT normalized by the PTT of the heart (PTTn: kidney PTT/heart PTT), and the change in the reciprocal of PTTn (1/PTTn) were used as indices of the change in RBF. The resting RBF was also measured simultaneously by both RA and the para-aminohippuric acid (PAH) clearance method (CPAH). Post-exercise RBF was measured only by RA within 60 s of exercise, then again within 30 and 60 min of exercise on different days, since RBF can be measured successively only three times even with the use of 99 mTc-phytate. The resting value of 1/PTTn was converted to the value of CPAH corrected for haematocrit, and post-exercise change of 1/PTTn (RBF) was represented as a change in the value of CPAH in order to express a definite numerical change, rather than a percentage change, from resting RBF. The RBF decreased by 53.4% immediately after exercise, and remained decreased by 17.5% 30 min after and by 21.1% 60 min after exercise in comparison with the resting value. The RBF was found to be correlated with changes in Ccr (r = 0.773, P < 0.001), UV (r = 0.598, P < 0.001), and the concentrations of plasma angiotensin II (r = -0.686, P < 0.001) and noradrenaline (r = 0.652, P < 0.001) after exercise. However, there were no significant correlations between the changes in plasma aldosterone ([Ald]) and plasma noradrenaline, or in [Ald]p1 and plasma angiotensin II concentrations. The change in [Ald]p1 did not coincide with the variation in reabsorption of Na+ in the renal tubules. Results of the present study showed that change in Ccr after exhausting exercise depended mainly on change in RBF and that changes in UV and osmolality after exhausting exercise were induced not only by change in RBF, but also by changes in reabsorption of water and solutes in the renal tubules. It is suggested that changes in reabsorption of water and solutes might be influenced by metabolites induced by exercise and an increased release of hormones, other than aldosterone, involved in the regulation of renal function.

Adult↗