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Biomedical subjects

Y Choi

Publications and source records attributed to Y Choi.

At least 307 records · Page 17Linked to original sources

Correlation of ultrasound and renal scintigraphy in children with unilateral hydronephrosis in primary workup.

Ultrasound accurately detects hydronephrosis in infants and children, while nuclear medicine techniques quantify relative renal function in addition to characterizing the urodynamic relevance of hydronephrosis. This prospective study was undertaken to examine the relationship between ultrasound morphological findings and relative renal function, quantified with dynamic 99mtechnetium mercaptotriacetylglycine imaging, in the initial diagnostic workup of children with unilateral hydronephrosis. The ultrasound grade of hydronephrosis and relative renal function ipsilateral to the hydronephrosis were inversely related, indicating that with more severe hydronephrosis ultrasound fails to estimate the potential reduction of relative kidney function. Because renal function is not necessarily affected by hydronephrosis, renal scintigraphy is indicated to assess the functional status of hydronephrotic kidneys.

Child↗

Partial hypoxanthine-guanine phosphoribosyl transferase deficiency in two Korean siblings--a new mutation.

Two Korean siblings with partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency are reported. The index patient was a boy aged 9 years 10 months who developed acute renal failure with a serum uric acid level of 25.9 mg/dl, after vomiting. The younger brother was asymptomatic but had elevated serum uric acid (9.4 mg/dl). The red blood cell HPRT activity of both siblings was one-tenth of normal. Analysis of genomic DNA revealed a point mutation from A (adenine) to G (guanine) at nucleotide position 215 on exon 3; this is a new mutation. The younger brother had the same mutation and the mother was heterozygous for this mutation.

Acute Kidney Injury↗

Positron emission tomography: a new method for determination of renal function.

Positron emission tomography (PET) is a newly evolving diagnostic modality that has been widely used in many facets of clinical medicine, but whose use in the diagnosis and management of disorders of the kidney has not been previously described. Employing the radiotracer N-13 ammonia, flow-dependent extraction of this compound after intravenous injection was used to measure renal blood flow (RBF) in a swine model (N = 10). A mean baseline value of 3.16 ml./min./gm. kidney was obtained with this method, in close agreement with values previously reported using established invasive techniques. Four conditions known to affect RBF were also studied to determine the ability of PET to detect changes in RBF. Kidneys were subjected to varying durations of warm ischemia, demonstrating a progressive decrease in RBF with increasing ischemic insult, with return to normal significantly impaired in animals exposed to the greatest degree of ischemia (180 minutes versus 150 or 120 minutes ischemia). Cross-transplant between animals produced acute allograft rejection and a corresponding marked decrease in RBF that failed to normalize. After unilateral nephrectomy, RBF increased two-fold in the remaining kidney by 7 days (R = 0.79), as predicted for compensatory renal hypertrophy. Lastly, there was an inverse, linear relationship between toxic cyclosporine level and RBF (R = 0.68), indicative of vascular-mediated cyclosporine nephrotoxicity. Positron emission tomography is safe and efficient, and yields an accurate measurement of RBF in several important physiologic states. The development of PET as a quantitative measure of renal function is promising.

Animals↗

Quantification and parametric imaging of renal cortical blood flow in vivo based on Patlak graphical analysis.

Patlak graphical analysis was applied to quantify renal cortical blood flow with N-13 ammonia and dynamic positron emission tomography. Measurements were made in a swine model of kidney transplantation with a wide range of normal and abnormal renal blood flows (N = 57 studies) and in 20 healthy human volunteers (N = 45 studies). Estimates of renal cortical blood flow by the Patlak method were compared to those from a two-compartment model for N-13 ammonia. In addition, estimates of renal cortical blood flow by the N-13 ammonia PET approach were compared in 10 normal human volunteers to estimates by the metabolically inert, freely diffusible O-15 water and a one-compartment model. Patlak graphical analysis estimates of renal cortical blood flow correlated linearly with the standard two-compartment model in pigs (y = -0.05 + 1.01x, r = 0.99) and in humans (y = 0.57 + 0.88x, r = 0.93). Estimates of renal cortical blood flow by O-15 water in human volunteers were also linearly correlated with those by N-13 ammonia and the Patlak graphical analysis (y = 0.71 + 0.84x, r = 0.86). Renal cortical blood flow estimates were highly reproducible both with N-13 ammonia and O-15 water measurements in humans. It is concluded that the Patlak graphical analysis with N-13 ammonia dynamic positron emission tomograpic imaging renders accurate and reproducible estimates of renal cortical blood flow. Moreover, the graphical analysis approach is 1,000 times faster than the standard model fitting approach and suitable for generating parametric images of renal blood flow in the clinical setting.

Adolescent↗

The bacterial and mouse mammary tumor virus superantigens; two different families of proteins with the same functions.

In conclusion, the bacterial toxins are completely unlike the MTV superantigens in primary sequence and structure. The former are soluble globular proteins which do not have to be proteolytically cleaved before they act. The latter are synthesized as type II membrane proteins and may be clipped before they reach the cell surface and act to stimulate T cells. Table III summarizes the similarities and differences between the two sets of superantigens. The most notable quality of these molecules is that both sets of families have developed strategies whereby they bind to Class II and engage V beta. As far as the microorganisms which produce them are concerned, these two properties appear to be essential since they are absolutely conserved over proteins of a number of different structures. Several questions can now be addressed as follows. a. Why do all known superantigens bind to Class II? For the microorganism which produces them, the function of superantigens appears to be T-cell and perhaps directly or indirectly B-cell and macrophage stimulation. Activation of virgin T cells requires engagement with antigen plus MHC on professional antigen-presenting cells. Unlike other cell surface proteins, for example Class I, most Class II in animals is expressed on such cells. Therefore it is likely that superantigens have evolved to engage Class II because presentation to T cells by Class II-bearing cells offers the superantigen the best chance of activating its target T cells. b. Why do superantigens engage TCR V beta and not V alpha or CD3? It is possible that superantigens bind to the V beta portion of the TCR rather than V alpha because the latter does not have a consistently well exposed face for engagement. The fact that it is perhaps relatively easier to produce anti-V beta rather than anti-V alpha antibodies supports this idea. We have shown that N-glycosylation of V beta can interfere with recognition by vSAGs (Pullen et al. 1991), perhaps glycosylation of V alpha tends to conceal otherwise available sites. As far as C beta, C alpha or CD3 engagement is concerned, this may be just too dangerous for MTVs. The role of MTVs SAgs in the life history of the virus seems to be to stimulate T cells in the suckling recipient and thereby create a pool of activated lymphocytes in which the virus may survive until the mouse gives birth and transmits the virus to her own progeny (Hainaut et al. 1990, Golovkina et al. 1992).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Identification of surface-exposed B-cell epitopes recognized by Haemophilus influenzae type b P1-specific monoclonal antibodies.

A panel of P1 synthetic peptides was synthesized to map the surface-exposed epitopes of Haemophilus influenzae type b outer membrane protein P1 recognized by three murine monoclonal antibodies (MAbs 7C8, 3E12, and 6B1). By using peptide-specific enzyme-linked immunosorbent assays, MAbs 6B1, 7C8, and 3E12 were shown to recognize distinct epitopes localized within residues 60 to 88, 165 to 193, and 400 to 437 of mature P1, respectively. Since MAb 7C8 was shown previously to be protective against certain H. influenzae type b subtypes in the infant rat model of bacteremia, its cognate epitope was further characterized by using truncated peptide analogs. Fine mapping of the 7C8 epitope by competitive inhibition studies revealed that it was localized within residues 184 and 193.

Amino Acid Sequence↗

Extracranial head and neck: PET imaging with 2-[F-18]fluoro-2-deoxy-D-glucose and MR imaging correlation.

The aim of this study was to define and quantitate the normal anatomy of the extracranial head and neck with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). This information was used to study 12 patients with primary squamous cell carcinomas. In all cases, the lymphoid tissue of the Waldeyer ring and the palatine and lingual tonsils could be differentiated from the airway, striated muscle, osseous structures, and salivary glands. Striated muscle had markedly less activity than lymphoid or salivary gland tissue. In the 12 patients with primary tumors, FDG PET depicted the tumor as an area of increased activity significantly higher than that of normal tissue. In one instance, FDG PET allowed detection of a tumor not seen at magnetic resonance (MR) imaging or computed tomography. Of the 34 lymph nodes positive for carcinoma, 24 were positive according to MR size criteria and 25 were detected with FDG PET. FDG PET allowed detection of three nonenlarged metastatic nodes that were negative at MR imaging.

Contrast Media↗

Change induced by radiation therapy in FDG uptake in normal and malignant structures of the head and neck: quantitation with PET.

PURPOSE: To quantitate the changes induced in uptake of the glucose analog 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in normal structures in the head and neck and compare these to the change in uptake in malignant structures in patients with head and neck tumors undergoing radiation therapy. MATERIALS AND METHODS: Eleven patients with biopsy-confirmed squamous cell carcinoma of the head and neck were studied before, during, and after a 6-week course of radiation therapy with positron emission tomography (PET)-FDG imaging. A ratio of FDG uptake in the structure compared with that in the cerebellum (termed metabolic ratio) within and outside of the field of radiation was determined in the adenoids; lingual and palatine tonsils; parotid, submandibular, and sublingual glands; and nasal turbinates, soft palate, and gingiva. RESULTS: The average metabolic ratio in the tonsils, nasal turbinates, soft palate, and gingiva did not change significantly with treatment. CONCLUSION: FDG uptake in normal structures does not change with radiation therapy. This fact is in marked contrast to the FDG uptake in squamous cell carcinomas in the head and neck, which decrease dramatically with treatment (P < .005).

Adenoids↗

Bone metabolic activity measured with positron emission tomography and [18F]fluoride ion in renal osteodystrophy: correlation with bone histomorphometry.

We evaluated the bone metabolic activity in patients with renal osteodystrophy using positron emission tomography and [18F]fluoride ion. Eight patients had secondary hyperparathyroidism (HPT), and three had low-turnover bone disease. Eleven normal subjects were also studied, and three of the eight HPT patients were reevaluated after therapy. A rate constant (K) describing the net transport of [18F] fluoride ion into a bound compartment in bone was calculated using both a three-compartment model and Patlak graphical analysis. Values of K were compared with biochemical data and with histomorphometric indices. The results indicate that K is significantly higher (P < 0.01) in HPT patients than in normal subjects and patients with low-turnover bone disease. Values of K correlated with serum alkaline phosphatase (r = 0.81) and PTH (r = 0.93) levels and with histomorphometric indices of bone formation rate (r = 0.84, P < 0.01) and eroded perimeter (r = 0.77, P < 0.05). Values of K decreased by 40 and 30%, respectively, in two patients who underwent parathyroidectomy and medical therapy. Positron emission tomography studies of bone using [18F]fluoride ion can differentiate low turnover from high turnover lesions of renal osteodystrophy and provide quantitative estimates of bone cell activity that correlate with histomorphometric data.

Adolescent↗

Hallervorden-Spatz syndrome in two siblings diagnosed by the clinical features and magnetic resonance imaging (MRI).

Hallervorden-Spatz syndrome (HSS) is a heredodegenerative disorder characterized by both progressive pyramidal and extrapyramidal signs, dysarthric speech, and mental deterioration. No diagnostic biochemical test is yet available, and diagnosis of HSS can be confirmed only at autopsy by the characteristic neuropathology including abnormal iron storage, disordered myelination, and loss of brain substance. We present two siblings with clinical features consistent with HSS, in whom magnetic resonance imaging (MRI) demonstrated the deposition of iron in the globus pallidus and the substantia nigra thus allowing an antemortem diagnosis of HSS.

Child↗

Automated iterative three-dimensional registration of positron emission tomography images.

Two types of image similarity measures, the sum of absolute differences (SAD) and the stochastic sign change (SSC), were compared for three-dimensional registration of images from PET. To test the accuracy of both registration methods, 30 FDG brain studies, 40 13N-ammonia cardiac studies and 20 FDG liver tumor studies (where each image set contained 15 image planes, 128 x 128 pixels per plane) were made into worse case conditions by creating image sets of low counts and extreme defects. These images were then registered to the reference images that had been moved in three dimensions into a random set of known translations, rotations and normalization factors (x, y, z, theta, rho, sigma, nf). Neither method required any external fiduciary markers or operator interventions to register a set of images. The optimization of the image similarity (using the SAD or SSC) was performed with the simplex method and registration was completed within 10 min of computation time on a low-end workstation. Overall, the SAD method had an average inplane (x, y) registration error of 0.5 +/- 0.5 mm, a z-axis registration error of 1.1 +/- 1.1 mm, an inplane rotational error of 0.5 +/- 0.4 degrees, an out-of-plane rotational error of 1.1 +/- 1.2 degrees and a normalization factor error of 0.015 +/- 0.016. The SSC method had an average inplane (x, y) registration error of 0.6 +/- 0.5 mm, a z-axis registration error of 1.1 +/- 1.1 mm, an inplane rotational error of 0.7 +/- 0.5 degrees, an out-of-plane rotational error of 1.0 +/- 1.2 degrees and a normalization factor error of 0.014 +/- 0.014. This study demonstrates that either the SAD or SSC method for measuring image similarity, combined with the simplex method for function optimization, are accurate methods for registration of a wide variety of PET images including low count studies and those with marked interval changes in the pattern of count distribution.

Brain↗

A refined method for quantification of myocardial oxygen consumption rate using mean transit time with carbon-11-acetate and dynamic PET.

The utility of the mean transit time equation was investigated for estimation of the myocardial clearance rate constant of 11C-acetate, which is proportional to myocardial oxygen consumption rates. The mean transit time approach was also employed to generate parametric images of the clearance rate constant of 11C-acetate with dynamic PET imaging in 20 normal human studies. Input function delays and cutoff errors due to the truncation of the myocardial tissue time-activity curve at a finite time were corrected. The clearance rate constants estimated by mean transit time correlated well with the estimates by conventional monoexponential fitting (15 min (truncation time): Y = 0.01 + 0.94X, correlated coefficient (r) = 0.99; 16 min: Y = 0.03 + 0.94X, r = 0.98; 20 min: Y = 0.03 + 0.84X, r = 0.99). The clearance rate constants estimated by the mean transit time approach also correlated well (r = 0.94) with the measured rate-pressure products. The quality and noise level of parametric images of the clearance rate constants generated by mean transit time are improved over those generated by monoexponential fitting. Additional advantages of the mean transit time approach compared to the standard monoexponential fitting method for estimating myocardial clearance rate constant of 11C-acetate include ease of input function delay correction, less sensitivity to the shape of the input function and elimination of subjective data selection of the linear portion of the clearance data on a semilog plot. Thus, this approach is expected to facilitate objective quantitative analysis of indices of myocardial oxygen consumption.

Acetates↗

A simplified method for quantification of myocardial blood flow using nitrogen-13-ammonia and dynamic PET.

The utility of Patlak graphical analysis was investigated for quantification of regional myocardial blood flow (MBF) and for generating parametric images of MBF with 13N-ammonia and dynamic PET imaging in dogs and humans. MBF was estimated by a two-compartment model fit of the initial 2 min of the kinetic data and by Patlak graphical analysis of the initial 2, 3, or 4 min of data. In 11 dog studies, MBF by compartmental model fitting linearly correlated with MBF by microspheres (correlation coefficient (r) = 0.99, slope = 0.92) and by Patlak graphical analysis (r = 0.99, slope = 0.90). In 10 normal human studies, MBF obtained by the Patlak graphical analysis agreed well with MBF obtained by the compartmental model fitting (r = 0.96, slope = 1.04). Good agreement of the MBF estimates was also observed in 10 coronary artery disease patient studies (r = 0.96). Patlak graphical analysis permitted generation of parametric images of MBF. The parametric images of MBF, in units of ml/min/g, are of good image quality and have relatively low noise levels. We conclude that regional MBF can be noninvasively and conveniently measured with dynamic 13N-ammonia PET using either a two-compartment model or Patlak graphical analysis. MBF parametric images generated with the Patlak graphical analysis both map the distribution and quantitate the magnitude of myocardial perfusion abnormalities.

Adult↗

Structural analysis of a mouse mammary tumor virus superantigen.

It has recently been shown that the minor lymphocyte stimulating-like products expressed by some mice are actually encoded by open reading frames in the 3' long terminal repeats of mouse mammary tumor viruses. These products act as viral superantigens (vSAGs). That is, they stimulate most T cells bearing particular V beta s almost regardless of the rest of the variable components of the T cell receptors expressed by those cells. To find out more about the structure of these vSAGs, a set of truncated vSAG genes was used in transfection and in vitro translation experiments to show that the functional vSAG is a type II integral membrane protein with a large glycosylated extracellular COOH-terminal domain and a small, nonessential, intracellular NH2-terminal cytoplasmic domain. These results are consistent with the fact that the vSAGs must be expressed on the cell surface in order to interact with T cells and class II major histocompatibility complex proteins. They also account for the finding that much of the V beta specificity of the vSAGs is controlled by amino acids at the COOH-terminal end of the vSAG proteins, amino acids that will be extracellular in type II proteins.

Amino Acid Sequence↗

The open reading frames in the 3' long terminal repeats of several mouse mammary tumor virus integrants encode V beta 3-specific superantigens.

Mice expressing the minor lymphocyte stimulation antigens, Mls-1a, -2a, or -3a, singly on the B10.BR background have been generated. Mls phenotypes correlate with the integration of mouse mammary tumor viruses (MTV) in the mouse genome. The open reading frames within the 3' long terminal repeats of the integrated MTVs 1, 3, 6, and 13 encode V beta 3-specific superantigens. Sequence data for these viral superantigens is presented, indicating that it is the COOH-terminal portion of the viral superantigen that interacts with the T cell receptor V beta element.

Amino Acid Sequence↗

The role of positron emission tomography in oncology and other whole-body applications.

Imaging and quantifying biochemical and physiological processes with PET clearly has major potential significance for all organ systems and many disease states. Although the full utility and potential of emerging new applications of PET in organs other than the heart and brain must be demonstrated in basic and clinical research studies, the rapidly accumulating aggregate experience in oncology in particular, and in other organ systems and disease states as well, indicates that PET is now truly becoming a modality of both clinical and investigative use for the body as a whole as well as for specific organ systems. Whole-body PET FDG imaging (Fig 9) illustrates the potential of biochemical imaging to map the distribution of cancer throughout the body. With the growing list of radiopharmaceutical and quantitative techniques applicable to cancer studies with PET, this field will continue to realize significant growth.

Humans↗