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PubMed1985

[The use of 99mTc-dimercaptosuccinic acid renoscintigraphy in the evaluation of differential renal function].

We studied the total and differential renal function by 99mTc-dimercaptosuccinic acid (DMSA) renoscintigraphy and present a formula to estimate the renal depth for the Japanese and the attenuation coefficient which influenced renal uptake. Total renal uptake of 99mTc-DMSA correlated well with creatinine clearance and with the PSP test, and there was a close correlation between its relative uptake and relative function as determined by 99mTc-diethylenetriaminepentaacetic acid (DTPA) renography. Therefore differential renal function test with 99mTc-DMSA renoscintigraphy was found to have clinical utility. We also demonstrated 99mTc-DMSA renoscintigraphy provided useful morphological information.

Adolescent↗
PubMed1991

Quantitation of differential renal function with Tc-99m MDP.

This study was designed to evaluate the usefulness of the bone tracer Tc-99m MDP for quantitative assessment of relative renal function as compared with renal imaging radiotracers used for that purpose. Differential renal function, i.e., the percent contribution each kidney makes to global renal function, was determined prospectively in 15 consecutive patients using Tc-99m MDP and a renal radionuclide tracer, either Tc-99m DTPA or Tc-99m GHA. Differential function was computed in all cases from the early (1-3 minutes) renal uptake of the tracers by region-of-interest analysis of the computer-acquired data. There was a high correlation between values of differential function obtained with Tc-99m MDP and those obtained with Tc-99m DTPA or Tc-99m GHA (r = 0.98, P less than 0.0001). Qualitative assessment of the images revealed equivalent scintigraphic patterns in all patients. It is concluded that the early characteristics of renal handling of Tc-MDP are sufficiently similar to those of Tc-DTPA and Tc-GHA so that accurate estimates of differential renal function are possible with this agent, and that Tc-MDP-determined renal differential most likely reflects differential glomerular filtration rate.

Aged↗
PubMed1996

The effect of in vitro human immunodeficiency virus infection on dendritic-cell differentiation and function.

CD1a+ dendritic cells (DC) differentiate from a major population of nonadherent CD13(hi)lin- cells that appear when human cord blood CD34+ hematopoietic progenitor cells are cultured with stem-cell factor, granulocyte/macrophage (MA) colony-stimulating factor, and tumor necrosis factor-alpha (TNF-alpha) for 5 days. CD13hilin- cells, which also comprise MA and granulocyte precursors, are CD4+ and can thus be targets of human immunodeficiency virus (HIV). Low replication was noted when these day 5 cells were infected with lymphotropic HIV-1LA1 (p24: < or = 4 ng/mL on day 8 postinfection [PI]), while high virus production occurred with MA-tropic HIV-1Ba-L, HIV-1Ada, or HIV-1-m-n. (p24: 50 to > or = 1,000 ng/mL). Strong cytopathicity (CPE) was then observed in nonadherent cells as in adherent MA. However, FACS analysis on day 7 PI showed that HIV did not affect differentiation of DC that survived CPE: apart from CD4 downmodulation related to HIV production, overall expression of CD40, CD80, and CD86 costimulatory molecules, and of HLA-DR, was unchanged relative to controls. At that time, the capacity of DC from HIV-infected cultures to stimulate the mixed leukocyte reaction was only altered less than 10-fold. Immunocytochemistry on day 7 PI showed that most HIV-infected cells were included in syncytia that were stained by anti-CD1a, anti-S100, and anti-CD14 antibodies, indicating that syncytia consisted of DC and cells of the MA lineage. Polymerase chain reaction analysis of FACS-sorted CD1a+ cells confirmed that they harbored then HIV DNA. Viral DNA was also detected in CD1a+ DC from noninfected cultures that had been exposed to HIV only after sorting. Therefore, we examined whether in infected cultures DC precursors were infected at the onset or if virus spread later from other infected cells to differentiated DC. This was answered by showing that, 24 hours postexposure to HIV, viral DNA was preferentially detected in day 5 sorted CD13hilin- versus CD13hilin- cells, and that it was found in the CD1a+ progeny of CD13(hi)lin- cells 48 hours later. In addition, HIV replication did not affect myeloid clonogenic progenitors in day 0 to day 7 PI cultures, although viral DNA was detected in colony-forming unit-granulocyte/macrophage (CFU-GM)/CFU-M colonies derived from day 3 and 7 PI cultures. Thus, precursors of DC and their progeny are susceptible to HIV in vitro, but, apart from CPE, the effect of virus production on DC differentiation or function is limited.

Antigens, CD↗
PubMed2002

Effect of the size of regions of interest on the estimation of differential renal function in children with congenital hydronephrosis.

The estimation of differential renal function from dynamic renography affects clinical decisions. The estimation requires the kidneys to be delineated with regions of interest. However, in the presence of unilateral hydronephrosis it is not unusual for the affected kidney to be enlarged so that the regions of interest required to delineate the normal and abnormal kidneys are themselves dissimilar in size. The question, which then arises is, will this difference in the sizes of the regions of interest affect the resultant estimation of differential renal function? Eighteen children aged 1 month to 7 years, with prenatal ultrasound diagnosis of unilateral hydronephrosis where the affected kidney was larger than the normal kidney, underwent a total of 57 diuretic renograms using 99mTc-mercaptoacetyltriglycine. The renographic data were retrieved from optical disc and re-analysed. Regions of interest were generated which enclosed each kidney plus a region of interest of equal size to the abnormal large kidney was placed over the normal kidney. The consensus report from the Scientific Committee of Radionuclides in Nephrology described the Rutland-Patlak plot and integral methods for the estimation of differential renal function from dynamic renography. These two methods were used to analyse renal curves with and without background subtraction. Evaluation of the results suggest that technical factors, including the size of the region of interest, may affect differential renal function, and may, in part, explain the reports of the super-normal kidney in the literature.

Child↗
PubMed1988

The regulation and integration of thyroid follicular differentiation and function.

As in a number of other endocrine tissues in which expression of differentiated function is dependent upon a stable cellular architecture, the control of differentiation of the thyroid follicle requires a coordination between the ultrastructural and morphological responses to a number of endocrine growth factors, which may ultimately involve autocrine or paracrine-mediated effects within the immediate follicular microenvironment. Through analogy with other cell types, expression of appropriate differentiation characteristics within the thyroid follicle may involve the activation of specific c-oncogenes within each of the component cells. With the recent development and application of oncogene transfection technology, application of such procedures to the thyroid follicular cell should prove to be a particularly fruitful area for future research within the thyroid gland, leading to elucidation of the mechanisms whereby the cellular responses to growth and tissue-differentiating factors are mediated. Clearly however, further consideration must also be made of the roles played in maintaining follicular stability by both physical and chemical interactions between the component cells and the immediate extracellular environment. The contributory roles played by basement membrane and cell-surface components in cellular recognition, together with the physical effects imposed upon the apical surfaces of the follicle by luminal thyroglobulin have already been identified as fundamental factors in this respect. It is also readily apparent that morphological differentiation of the follicle bears critically upon the chemical characteristics of the microenvironment through the ability of the latter to promote expression of specific apical/basal recognition characteristics of the component cells, and thus maintain the unidirectional polarity upon which the functional capacity of the thyroid follicle is so critically-dependent.

Cell Differentiation↗
PubMed2002

Noninvasive differentiation of normal from pseudonormal/restrictive mitral flow using TEI index combining systolic and diastolic function.

Differentiation of normal from pseudonorma/restrictive mitral flow is not necessarily easy. Pseudonormal/restrictive flow is usually associated with left ventricular (LV) dysfunction, which can be detected using the TEI index, combining systolic and diastolic function. The purpose of this study was to test the feasibility of using the TEI index to differentiate pseudonormal/restrictive from normal mitral flow. In 33 patients with mitral flow E/A > or = 1 and LV mid-diastolic pressure measured by catheterization, the LV volumes, mitral E and A velocity, deceleration time of the E velocity, and the TEI index, defined as the sum of the isovolumic contraction and relaxation time divided by ejection time, were evaluated using Doppler echocardiography. Pseudonormal/restrictive mitral flow was defined as mitral flow E/A > or = 1 associated with LV mid-diastolic pressure > 12 mmHg. There were 22 and 11 patients with normal and pseudonorma/restrictive mitral flow, respectively. Among the indices of LV function, the TEI index achieved the best correlation with LV mid-diastolic pressures (r2 = 0.63, p < 0.0001). By setting the TEI index > or = 0.65 as the criteria for pseudonormal/restrictive mitral flow, this diagnosis had sensitivity, specificity, and accuracy of 82%, 96%, and 91%, respectively. TEI index allows noninvasive differentiation of pseudonormal /restrictive from normal mitral flow.

Aged↗
PubMed2001

Supranormal differential renal function is real but may be pathological: assessment by 99m technetium mercaptoacetyltriglycine renal scan of congenital unilateral hydronephrosis.

PURPOSE: It is unclear whether supranormal differential renal function of the hydronephrotic kidney is real or artifactual. We investigated the effect of clinical and renographic parameters on differential renal function. MATERIALS AND METHODS: The study included 34 males and 10 females from 1 to 9 months old (median age 2.6 months) with unilateral congenital hydronephrosis. A 99mtechnetium (Tc) mercaptoacetyltriglycine (MAG3) scan was performed, and regions of interest were drawn on the kidneys, and perirenal and lateral backgrounds. Differential renal function was calculated with and without background subtraction at 30-second intervals from 0.5 to 3 minutes after injection of 99mTc-MAG3. The effects of age, sex, obstruction, site and size of the hydronephrotic kidney were analyzed using the generalized estimating equations method. RESULTS: There were 11 right and 33 left hydronephrotic kidneys. An obstructive renographic pattern was present in 33 cases. The trends of differential renal function according to intervals were different between kidneys with and without background subtraction, and differential renal function increased significantly as size increased (p <0.05). Differential renal function of the hydronephrotic kidney with an obstructive renographic pattern increased with time when perirenal or no background subtraction was applied (p <0.05). The effects of age, sex or laterality on differential renal function were not significant. Supranormal function (differential renal function 55% or greater) was present regardless of background subtraction methods and measurement time. CONCLUSIONS: Differential renal function is higher in larger hydronephrotic kidney but function of the kidney with an obstructive pattern is overestimated on later phases of 99mTc-MAG3 renal scan. Supranormal differential renal function is real and may be pathologic since it is prone to occur in larger obstructive hydronephrotic kidneys.

Diuretics↗
PubMed1995

A technique for porcine hepatocyte harvest and description of differentiated metabolic functions in static culture.

Current bioartificial liver devices are based on the use of a large mass of hepatocytes exhibiting differentiated metabolic function. The pig has become a source of interest for the acquisition of such cells-however, harvesting a large mass of highly viable cells has met with difficulty. This study describes a technique for harvesting large quantities of hepatocytes at viabilities greater than 90% and also describes several features documenting differentiated function. Pigs, 6 to 10 kg body weight, underwent in situ two-step whole liver perfusion (ethylene glycol tetraacetic acid and collagenase) and ex vivo cell harvest. Harvests yielded an average of 19.5 billion cells with an average viability of 94.6%. Hepatocytes were then entrapped in type I collagen (3 x 10(5) cells/well) and cultured in serum-free media for 5 days. Pig hepatocytes produced stable amounts of albumin and maintained cytochrome P-450 and glucuronidation activity over 5 days, as shown by the metabolism of lidocaine and 4-methylumbelliferone. These data indicate that pig hepatocytes can be harvested with high yields and can retain viability and differentiated function over at least 5 days of culture, and therefore should prove to be an excellent source of hepatocytes for bioartificial liver devices.

Animals↗
PubMed1999

Assessment of various parameters in the estimation of differential renal function using technetium-99m mercaptoacetyltriglycine.

Differential renal function (DRF) is an important parameter that should be assessed from virtually every dynamic renogram. With the introduction of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3), a tracer with a high renal extraction, the estimation of DRF might hopefully become accurate and reproducible both between observers in the same institution and also between institutions. The aim of this study was to assess the effect of different parameters on the estimation of DRF. To this end we investigated two groups of children: group A, comprising 35 children with a single kidney (27 of whom had poor renal function), and group B, comprising 20 children with two kidneys and normal global function who also had an associated 99mTc-dimercaptosuccinic acid scan (99mTc-DMSA). The variables assessed for their effect on the estimation of DRF were: different operators, the choice of renal regions of interest (ROIs), the applied background subtraction, and six different techniques for analysis of the renogram. The six techniques were based on: linear regression of the slopes in the Rutland-Patlak plot, matrix deconvolution, differential method, integral method, linear regression of the slope of the renograms, and the area under the curve of the renogram. The estimation of DRF was less dependent upon both observer and method in patients with two normally functioning kidneys than in patients with a single kidney. The inter-observer comparison among children in either group was not dependent on either ROI or background subtraction. However, in patients with poor renal function the method of choice for the estimation of DRF was dependent on background subtraction, though not ROI. In children with two kidneys and normal renal function, the estimation of DRF from the 24 techniques gave similar results. Methods that produced DRF values closest to expected results, from either group of children, were the Rutland-Patlak plot and matrix deconvolution methods.

Area Under Curve↗
PubMed1994

Contradictory supranormal differential renal function during nuclear renographic investigation of hydroureteronephrosis.

We selected a group of children with unilateral hydroureteronephrosis to assess the significance of the differential renal function as determined by nuclear renography as a factor in defining obstructive dilatation. All children who presented to our institution during a 21-month period with unilateral hydroureteronephrosis and a normal contralateral kidney were reviewed. Patients with reflux or bladder pathology were excluded, resulting in 13 evaluable patients younger than age 2 years. Diuretic renography was performed using 99mtechnetium-diethylenetriaminepentaacetic acid in accordance with the well tempered renogram. Ancillary studies included voiding cystourethrography, ultrasonography and/or excretory urography. Of the 13 patients 5 had a differential function greater than 55% in the hydronephrotic kidney. Ten of the 13 patients, including the 5 with supranormal function, underwent surgical correction in the form of ureteral reimplantation for recurrent infections, increasing hydronephrosis, decreasing or decreased function and loss of parenchyma. Stenotic distal adynamic ureteral segments with proximal dilatation were confirmed in all cases. The implication by nuclear renography that a dilated kidney has better function than its morphologically normal counterpart is at variance with any available clinical or experimental data. The etiology of this apparently elevated function is unclear and its presence on a renographic study should not be interpreted as suggestive that the kidney is free of risk of nephron loss. Management decisions should not be based solely on the differential function as determined by nuclear renography.

Child, Preschool↗
PubMed1997

Contracting in the National Health Service (NHS): recognizing the need for co-operation.

Within the reorganized National Health Service hierarchical relationships between Health Authorities and Trusts have been replaced by functional differentiation. However, differentiation of function cannot be seen as an end in itself and management of the relationship between purchasers and providers must include managing the differentiation as well as the function. This paper suggests that collaborative and administrative activities have a distinct role to play in health service management. The paper suggests that in health service management market strategies are likely to dominate in relation to resource allocation activities. The paper also argues that administrative strategies are likely to be necessary within the internal market system--to bridge the gap resulting from the differentiation of function.

Contract Services↗
PubMed2002

[Comparative study of differential renal function by DMSA and MAG-3 in congenital unilateral uropathies].

UNLABELLED: In congenital obstructed hydronephrosis, the assessment of the differential renal function (DRF) is essential to provide a prognosis or to determine surgical treatment. The most reliable method to measure the differential renal function is the isotopic study with DMSA. The MAG-3 is employed to evaluation renal elimination, although in the minutes 1-3 it also measures the differential renal function. OBJECTIVE: We compared the estimation of differential renal function by 99Tc-dimercapto-succinic acid (DMSA) and 99Tc-mercaptoacetyltriglycyne (MAG-3) methods in congenital unilateral uropathies. MATERIALS AND METHODS: We reviewed the results of 138 isotopic studies of children (age range: 0-9 years) with congenital unilateral uropathies: 67 cases were obstructed and 71 non-obstructed. In all of them were carried out match tests pairs with DMSA and MAG-3. Both series were divided into 4 groups: 1) DRF < 40%, 2) DRF 40-45%, 3) DRF 46-50% and 4) DRF > 50%. The measurement differential renal function correlation by DMSA and MAG-3 were analysed. RESULTS: The coefficient of correlation was 0.96 (P < 0.01) in obstructed unilateral uropathy and 0.92 (P < 0.01) in non-obstructed serie. CONCLUSIONS: The differential renal function measured with DMSA and MAG-3 has a close correlation in congenital unilateral uropathies. Therefore in obstructed types, differential renal function and half-time elimination can be reliable and sure studied with MAG-3, being unnecessary DMSA test, avoiding additional radiation to the children.

Child↗
PubMed1983

Analysis of cloned T cell function. II. Differential blockade of various cloned T cell functions by cyclosporine.

Cyclosporine has profound suppressive effects on selected in vitro functions of cloned T lymphocytes. Cyclosporine inhibits the antigen-induced proliferation of the helper T cell clone 12-11. The effective dose required to reduce this response by 50% (ED50) is 28 ng/ml. In contrast, the proliferation of clone 12-11 induced by exogenous growth factors in secondary mixed lymphocyte culture supernatant (2 degrees MLC SN), is relatively insensitive to cyclosporine (ED50 = 4600 ng/ml). Furthermore, cyclosporine abrogates both antigen-induced and mitogen-induced secretion of lymphokines by clone 12-11, indicating that cloned helper T cell function is sensitive to cyclosporine even when interactions between specific alloantigens and their cell surface receptors are bypassed with mitogen. The suppressive effect of cyclosporine is not limited to helper T cell clones. The cytolytic T lymphocyte (CTL) clone 5MD2-2 is also sensitive to cyclosporine. Again, cyclosporine (100 ng/ml) blocks the antigen-driven, but not the exogenous lymphokine-driven, component of clone 5MD2-2 proliferation. This suppression does not result from the occlusion of antigen receptors or from antigen deformation by cyclosporine, because clone 5MD2-2 remains capable of antigen-specific cytolysis in the presence of cyclosporine concentrations that can suppress its proliferation. Finally, the ability of clone 5MD2-2 to remove IL-2 activity from culture media, a function that is significantly enhanced by contact with specific alloantigen, is not influenced by suppressive cyclosporine concentrations.

Animals↗
PubMed1997

Estimation of differential renal function in children with a prenatal diagnosis of unilateral pelvic dilatation.

PURPOSE: We compared the estimation of differential renal function by 99mtechnetium (Tc)-dimercapto-succinic acid (DMSA) and 99mTc-pentetic acid scintigraphic methods for followup of prenatally diagnosed unilateral renal pelvic dilatation. MATERIALS AND METHODS: We retrospectively analyzed differential renal function estimations calculated by static and dynamic methods in time matched test pairs that were included in the charts of 51 children monitored for prenatally diagnosed unilateral renal pelvic dilatation at our institution in a 5-year period. RESULTS: There were 96 test pairs with available archived raw data. Using the analytic method of assessment of agreement between the 2 tests, a 95% limit of agreement of +/-9% was calculated. Of the 96 pairs of tests the results of 94 revealed no significant difference. Subgroup analysis by patient age and operative intervention (13 postoperative pairs) also showed no difference in the results of the 2 tests. CONCLUSIONS: We established the 95% limits of agreement between 99mTc-DMSA and 99mTc-pentetic acid tests of differential renal function to be +/-9% discrepancy in 96 test pairs. During followup of prenatally diagnosed unilateral renal pelvic dilatation the assessment of differential renal function can be made by 99mTc-DMSA static or dynamic diuretic renography techniques. This interchangeability is consistent at all patient ages regardless of operative intervention. Since dynamic diuretic renography provides differential function and drainage data, using 99mTc-DMSA in this context is unnecessary and subjects patients to an unnecessary radiation burden.

Dilatation, Pathologic↗
PubMed2005

Role of the basic helix-loop-helix transcription factor, scleraxis, in the regulation of Sertoli cell function and differentiation.

Sertoli cells are a postmitotic terminally differentiated cell population in the adult testis that form the seminiferous tubules and provide the microenvironment and structural support for developing germ cells. The transcription factors that regulate Sertoli cell differentiation remain to be elucidated. The basic helix-loop-helix transcription factors are involved in the differentiation of a variety of cell lineages during development and are expressed in pubertal Sertoli cells. A yeast-two-hybrid procedure was used to screen a Sertoli cell library from 20-d-old pubertal rats to identify dimerization partners with the ubiquitous E47 basic helix-loop-helix transcription factor. Scleraxis was identified as one of the interacting partners. Among the cell types of the testis, scleraxis expression was found to be specific to Sertoli cells. Analysis of the expression pattern of scleraxis mRNA in developing Sertoli cells revealed an increase in scleraxis message at the onset of puberty. Sertoli cells respond to FSH to promote expression of differentiated gene products such as transferrin that aid in proper development of the germ cells. Analysis of the hormonal regulation of scleraxis expression revealed a 4-fold increase in scleraxis mRNA in response to the presence of FSH or dibutryl cAMP in cultured Sertoli cells. An antisense oligonucleotide procedure and overexpression analysis were used to determine whether scleraxis regulates the expression of Sertoli cell differentiated gene products. An antisense oligonucleotide to scleraxis down-regulated transferrin promoter activity in Sertoli cells. A transient overexpression of scleraxis in Sertoli cells stimulated transferrin and androgen binding protein promoter activities and the expression of a number of differentiated genes. Observations suggest scleraxis functions in a number of adult tissues and is involved in the regulation and maintenance of Sertoli cell function and differentiation. This is one of the first adult and nontendon/chondrocyte-associated functions described for scleraxis.

Androgen-Binding Protein↗
PubMed2002

Regulation of osteoclast differentiation and function by receptor activator of NFkB ligand and osteoprotegerin.

The differentiation and functions of osteoclasts (OCs) are regulated by osteoblast-derived factors. Receptor activator of NFkB ligand (RANKL) is one of the key regulatory molecules in OC formation. Osteoprotegerin (OPG) is a novel secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis and binds to RANKL. We examined the biological actions of macrophage-colony-stimulating factor (M-CSF), RANKL, and OPG on the differentiation of OCs isolated from cocultures of mouse osteoblastic cells and bone marrow cells. Preosteoclasts (pOCs) and OCs were characterized by their ultrastructure and the expression of OC markers such as tartrate-resistant acid phosphatase (TRAP) and vacuolar-type H(+)-ATPase. pOCs formed without any additives expressed TRAP, but showed little resorptive activity on cocultured dentine slices. TRAP-positive pOCs treated with M-CSF began to fuse with each other, but lacked a ruffled border (RB) and showed almost no resorptive activity. pOCs treated with RANKL became TRAP-positive multinucleated cells, which expressed intense vacuolar-type H(+)-ATPase along the RB membranes and exhibited prominent resorptive activity. Such effects of RANKL on pOCs were completely inhibited by the addition of OPG. OPG inhibited RB formation in mature OCs and reduced their resorptive activity, and also induced apoptosis of some OCs. These results suggest that 1) RANKL induces differentiation of functional OCs from pOCs, 2) M-CSF induces macrophage-like multinucleated cells, but not OCs, 3) OPG inhibits RB formation and resorptive activity in mature OCs, 4) OPG also induces apoptosis of OCs, and 5) RANKL and OPG are, therefore, important regulators of not only the terminal differentiation of OCs but also their resorptive function.

Animals↗
PubMed1989

Ly-6: a multigene family in search of a function.

Differentiation antigens can be simply defined as cell surface antigens that distinguish one cell type from another. The Ly-6 family of cell surface antigens might easily be regarded as a prototype for the analysis of the function of differentiation antigens on immunocompetent cells. Although a number of studies with antisera, in the late 1970s, established that the Ly-6 antigens exhibit an unusual pattern of expression on T and B lymphocytes, functional studies failed to demonstrate that the expression of Ly-6 defines a unique subpopulation of immunocompetent cells. Paradoxically, the development of anti-Ly-6 monoclonal antibodies led to a further decline in interest in this group of antigens, as the complexity of the results relegated Ly-6 to the realm of the die-hard immunogeneticist. Over the past five years, interest in Ly-6 has been rekindled and in this review Ethan Shevach and Patricia Korty summarize recent studies on the serology, biochemical and molecular structure, and the function of the products of this multigene family.

Amino Acid Sequence↗