[Dose calculations in radioiodine therapy of benign thyroid diseases].
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Biomedical subjects
Publications and source records attributed to J T Nielsen.
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Ninety children referred to hospital with urinary tract infection (UTI) were investigated by iv urography (IVU), ultrasonography (US) and 99mTc dimercaptosuccinic acid scan (DMSA). Fifty-eight children also underwent micturating cystourethrography (MCUG). In 36 (40%) of the children, at least one result was abnormal. Abnormal findings were found in 29 children with IVU, in 10 with US and in 16 with DMSA. Six of the 58 children had vesicoureteric reflux (VUR) in 8 kidneys. In 16 children, IVU was the only examination with an abnormal result, and in 10 of these the findings were considered important for treatment or prognosis. IVU is an important supplement to US and DMSA in investigation programs for children with UTI. IVU should be performed in cases of renal scars, dilatations or in children with recurrent infections.
Eight patients were examined. Seven had verified rhinorrhoea and six had had one or more episodes of pneumococcal meningitis. In four of the patients a fistula could not be visualized by computed tomography. All eight patients had injections of iodine-123-labelled albumin by lumbar puncture. Tomoscintigraphy (SPET) was performed 3, 6 and 8-9 h after injection. After 6-8 h we were able to demonstrate a fistula in seven of the patients with verified rhinorrhoea and the findings were confirmed by a subsequent operation. In one of the patients we were not able to visualize any leak of cerebrospinal fluid into the nasal cavity. This patient was not operated upon and we were not able to verify the findings in this patient. The operated patients all did well after the operation with no relapse of meningitis. In conclusion, SPECT-cisternography after intralumbar injection of iodine-123-labelled albumin is a valuable diagnostic tool for the detection of small fistulae in patients with rhinorrhea.
The mechanism for renal handling of carboplatin was studied in 17 ovarian cancer patients treated with a combination of carboplatin and cyclophosphamide. Carboplatin and [51Cr]-ethylenediaminetetraacetic acid (EDTA) renal clearances were measured simultaneously during short intervals of from 45 to 120 min. A total of 131 clearance intervals were analyzed during 35 chemotherapy courses. The carboplatin/[51Cr]-EDTA clearance ratio (R) served as an indicator of the net tubular reabsorption (R less than 1) or secretion (R greater than 1). The R value was calculated for each sampling interval. No significant difference was found between interpatient and intertreatment variation. The intertreatment variation as tested against the variation in the short intervals by an F-test was highly significant. We calculated the average R value for each treatment and consequently based our results on a total of 35 observations. The mean R value was 0.77 (t-test for R = 1; P less than 0.001). We conclude that the renal elimination of carboplatin takes place by glomerular filtration followed by tubular reabsorption.
Renography with [99mTc] diethylenetriaminepenta-acetate (DTPA) was performed in 26 patients with renal artery stenosis (RAS), unilateral in 15 and bilateral in 11, and in 16 patients with essential hypertension with a normal renal angiogram. Nine of the patients with unilateral RAS were restudied after a successful percutaneous transluminal renal angioplasty (PTRA), i.e. complete removal of the stenosis and a normalization of the blood pressure without antihypertensive treatment. Single-kidney [99mTc]-DTPA clearance and parenchymal mean transit time (MTT) were determined at each examination. All patients were studied on two different days using the same procedure except that captopril 25 mg was given orally before renography at the second examination. In unilateral RAS captopril reduced single-kidney [99mTc]-DTPA clearance significantly on the affected side (-42.7%, median) but not on the unaffected side (-3.2%). In bilateral RAS single-kidney [99mTc]-DTPA clearance was reduced to the greatest extent on the most affected side (-43.0%) compared with the least affected side (-17.2%). In essential hypertension no significant changes were recorded on any side (-1.5% for both). After PTRA, single-kidney [99mTc]-DTPA clearance was not significantly changed by captopril either on the previously affected side (4.3%) or on the unaffected side. MTT was significantly prolonged after captopril on the affected side in unilateral RAS and on the most affected side in bilateral RAS, whereas no significant changes were found on the unaffected side in unilateral RAS, on the least affected side in bilateral RAS, or on any side in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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A serological survey using alloantisera specific for the H-2 class I antigens in Japanese wild mice. Mus musculus molossinus, revealed a high frequency of the H-2Kf antigen. This antigen has also been found in European wild mice, M. m. domesticus and M. m. musculus. In this survey, the H-2Kf antigen was characterized through the use of ten newly isolated monoclonal antibodies raised against cells of a Japanese wild mouse, and by Southern blot analysis using an H-2K locus-specific probe which hybridizes with the 3' end of the gene. The serologically identified H-2Kf antigens revealed several minor variations in reactivities to the monoclonal antibodies. However, all the antigens examined could be clearly separated into two types with respect to the restriction fragment length polymorphism (RFLP) pattern. The first type, found together with a single, characteristic RFLP pattern, was always associated with the presence of reactivity to one particular monoclonal antibody MS54. The second type, found to represent different RFLP patterns, is associated with the absence of reactivity to MS54. This concordance between the presence of an antigenic determinant and a particular RFLP was observed not only within Mus musculus subspecies but also in a different species: M. spretus, carrying the same antigenic determinant, gave an identical RFLP to that of the other MS54-positive Mus musculus subspecies. The data suggest that the antigenic determinant specific for MS54 is an ancient polymorphic structure which has survived the long period of diversification of Mus species (approximately 2-3 million years) without alteration, and is associated with a stable DNA structure at the 3' end of the H-2K gene.
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The effect of flow rate and perfused load on insulin absorption was studied in isolated proximal rabbit tubules. In one series of experiments tubules were perfused for 30 min with 125I-[A14]insulin at 3.6 ng/ml and at flow rates varying between 2.2 and 43.3 nl/min, thus varying both flow rate and the perfused load. In a second series of experiments the tubules were exposed to increasing loads of insulin at a fixed flow rate of 15 nl/min. In a third series of experiments two groups of tubules were exposed to identical perfused loads at two different flow rates. The results showed that absorption is linearly correlated with the perfused load in the ranges of flow rates and concentrations examined. The perfused load determined the magnitude by which the insulin was reabsorbed, whereas the flow rate determined the efficiency (fractional absorption) by which the protein was reabsorbed. At flow rates less than 5 nl/min the fractional absorption was greater than 65%, and at flow rates greater than 30 nl/min fractional absorption was less than 40%. Thus, there is an inverse relationship between flow rate and fractional absorption. The described effects of changes in flow rate and perfused load are suggested to be caused by concomitant changes in the mean luminal concentration.
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The present study was performed to quantitate and compare the luminal and the peritubular uptake of 125I-labeled insulin in isolated, perfused, proximal tubules from rabbit kidneys. 125I-insulin was added in physiological concentrations of 3.0-7.0 ng/ml or 59.0-89.5 ng/ml (high insulin concentrations) to either the perfusate or the bath fluid for 30 min. The luminal uptake in 30 min averaged 0.76 pg/mm at physiological concentrations and 18.0 pg/mm at high insulin concentrations. About 15-41% of the absorbed insulin was digested and less than 5% was transported from the lumen to the peritubular space as intact insulin. The peritubular binding/uptake of 125I-insulin at physiological and high concentrations in the bath was 0.136 and 0.318 pg, respectively. Addition of excess unlabeled insulin (10(-5) M) to the bath produced significant inhibition of binding (53.7%) at 7.0 ng/ml, but no inhibition at 89.5 ng/ml labeled insulin in the bath. This indicates that insulin is bound/absorbed at the basolateral membranes both by a saturable specific mechanism and a nonspecific, nonsaturable mechanism. The basolateral absorption constituted 15.2 and 1.8% of the total tubular extraction of insulin at physiological and high insulin concentrations, respectively. Electron microscope autoradiography showed that, after luminal as well as basolateral endocytosis, insulin was exclusively accumulated in endocytic vacuoles and lysosomes.
PSP, parotid secretory protein, and salivary amylase are the major secretory proteins of mouse parotid gland where they appear in a constant ratio. Here we describe the isolation of the PSP gene and show through expression analysis on this and the salivary amylase gene that the two genes are transcribed in a coordinate fashion in adult animals, whereas the activation profiles are different during postnatal development. An explanation is put forward that involves activation of the genes at different stages of the acinar cell differentiation, leading in adults to the maximal and thus proportionate expression.
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Isolated, perfused proximal tubules from rabbit were used to study the luminal endocytic uptake, digestion, and transcellular transport of 125I-lysozyme. Ten tubules were perfused for 20 min with 125I-lysozyme and [14C]inulin and then with tracer-free perfusate for additional 40 min before fixation. The uptake and digestion of lysozyme was calculated per millimeter tubule length. The transfer of intact lysozyme from perfusate to the bath was measured and compared with the transfer of inulin. Five tubules were processed for electron microscope autoradiography, and the grain distribution was analyzed quantitatively. The results show that 2.7% of the perfused amount of lysozyme was taken up, and 21.3% of the absorbed protein was digested. The present experiments demonstrate that the transfer of intact lysozyme from lumen to bath is not significantly different from the transfer of inulin. The autoradiographic analysis showed that lysozyme was localized mainly in endocytic vacuoles and lysosomes after 60 min of perfusion.
The amylase complex on mouse chromosome 3 encodes both salivary and pancreatic amylase. It appears that one active gene is present for salivary amylase, whereas pancreatic amylase in some strains is coded by at least 4, and perhaps by more than 10, genes. Strain YBR is different from other strains in that it produces twice as much salivary amylase. Pancreatic amylase in YBR is present as two different protein forms, A beta and B beta, the sum of which amounts to only one-third of that in, for instance, strain A/J. YBR chromosomal DNA was cloned in phage gamma, followed by restriction and heteroduplex analysis of recombinant phages carrying amylase genes. Among 32 phage isolates, 5 carried parts of the salivary amylase sequence. The remaining phage isolates contained pancreatic amylase-like sequences and represented three nonoverlapping genomic regions, i.e., one of 34 kb containing a complete gene, PAN-II beta; another of 41 kb with a complete but different gene, PAN-I beta, plus a truncated gene, PAN-psi 1; and finally, one of 23 kb with another truncated gene, PAN-psi 2. Parts of the amino acid sequence of A beta and B beta have previously been determined, and we report here the sequencing of a 4-kb DNA fragment from Pan-II beta which establishes that this gene codes for B beta.
The purpose of the present experiments was to study possible different pathways of intracellular transport of proteins after luminal and basolateral uptake in isolated rabbit proximal tubules. Tubules were exposed to cationized ferritin (CF) in the perfusion fluid and horseradish peroxidase (HRP) in the bath simultaneously or to HRP in the bath alone for 30 min. The peritubular fluid (bath) and perfusion fluid were then exchanged and the tubules either fixed immediately or allowed to function during chase-periods for 10, 20, 30, or 60 min before fixation to follow the migration of the proteins through the cells. The proteins were to a large extent found separated in different vacuoles and lysosomes at all time periods studied, indicating separate pathways after uptake via the luminal and basolateral membranes respectively. About 0.5% of the CF taken up by the cells was transported through the cells and became located in the intercellular spaces. HRP was transported from the peritubular fluid to the apical cytoplasm of the tubules indicated by a gradual accumulation of small HRP-containing vesicles, first in the basal part of the cells and then in the apical cytoplasm. In tubules perfused with both CF and HRP in the perfusate, the CF and HRP were found together in apical vacuoles and lysosomes. After perfusion with HRP alone, this tracer was found in similar large vacuoles and lysosomes in the apical cytoplasm, in contrast to the small HRP-filled vacuoles seen after uptake from the bath.
Luminal uptake and degradation of protein in proximal tubules is well documented. However, abluminal uptake has only been demonstrated in a few species and probably only amounts to a few percent of luminal absorption. To investigate this absorptive pathway, isolated perfused proximal tubules from rabbit kidney were exposed to either cationized ferritin or horseradish peroxidase in the bath for 30 min. The tubules were then fixed and processed for electron microscopy. Peroxidase and small amounts of ferritin were found in the intercellular spaces, in endocytic vesicles located in the abluminal part of the cells and in multivesicular bodies. No tracer was found in the lumina or in the apical part of the cells. The tubules were ultrastructurally intact thus excluding the possibility that the proteins were absorbed via the luminal endocytic pathway or as a result of damaged cell membranes. In conclusion, this study presents evidence that ferritin and peroxidase can be absorbed via the basolateral membranes in rabbit proximal tubules.