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Biomedical subjects

S O Yang

Publications and source records attributed to S O Yang.

At least 19 recordsLinked to original sources

An orally active cathepsin K inhibitor, furan-2-carboxylic acid, 1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide (OST-4077), inhibits osteoclast activity in vitro and bone loss in ovariectomized rats.

Human cathepsin K, a cysteine proteinase of the papain family, has been recognized as a potential drug target for the treatment of osteoporosis. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel antiresorptive drugs. Now, we report the pharmacological properties of OST-4077 [furan-2-carboxylic acid (1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide] as a novel selective cathepsin K inhibitor. Human and rat cathepsin K were inhibited in vitro by OST-4077 with the IC50 values of 11 and 427 nM, respectively. OST-4077 suppressed bone resorption induced by rabbit osteoclasts (IC50, 37 nM) but did not affect bone mineralization or cellular alkaline phosphatase activity in MC3T3-E1 cells. Parathyroid hormone-induced bone resorption was inhibited in a dose-dependent manner in thyroparathyroidectomized rats gavaged with a single dose of OST-4077 (ED50, 69 mg/kg). When given orally twice daily for 4 weeks to 3-month-old ovariectomized (OVX) rats, OST-4077 dose-dependently prevented bone loss, as monitored by bone densitometry, ash content, and urinary excretion of deoxypyridinoline. No change in serum osteocalcin in the OVX rats by OST-4077 suggested that bone formation might not be affected by the agent. In summary, OST-4077 selectively inhibited bone resorbing activities of osteoclasts and prevented bone loss induced by estrogen deficiency but did not affect bone formation. OST-4077, an orally active selective human cathepsin K inhibitor, may have the therapeutic potential for the treatment of diseases characterized by excessive bone loss including osteoporosis.

Alkaline Phosphatase↗

Dopamine transporter density is decreased in parkinsonian patients with a history of manganese exposure: what does it mean?

Manganese (Mn) exposure can cause parkinsonism. Pathological changes occur mostly in the pallidum and striatum. Two patients with a long history of occupational Mn exposure presented with Mn-induced parkinsonism. In one patient, magnetic resonance imaging (MRI) showed findings consistent with Mn exposure, and Mn concentration was increased in the blood and urine. However, this patient's clinical features were typical of idiopathic Parkinson disease (PD). Previous pathological and positron emission tomography studies indicate that striatal dopamine transporter density is normal in Mn-induced parkinsonism, whereas it is decreased in PD. Therefore, we performed [(123)I]-(1r)-2 beta-carboxymethoxy-3beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) single-photon emission computed tomography. Severe reduction of striatal beta-CIT binding was indicated, which is consistent with PD. We propose three interpretations: (1) the patients have PD, and Mn exposure is incidental; (2) Mn induces selective degeneration of presynaptic dopaminergic nerve terminals, thereby causing parkinsonism; or (3) Mn exposure acts as a risk of PD in these patients. Our results and careful review of previous studies indicate that the axiom that Mn causes parkinsonism by pallidal lesion may be over-simplified; Mn exposure and parkinsonism may be more complex than previously thought. Further studies are required to elucidate the relationship between Mn and various forms of parkinsonism.

Causality↗

Use of Tc-99m HMPAO leukocyte scans to evaluate bone infection: incremental value of additional SPECT images.

PURPOSE: In this study, the diagnostic value of Tc-99m hexamethylpropylene amine oxime (HMPAO) leukocyte scans and the role of additional SPECT in the diagnosis of bone infection were evaluated. MATERIALS AND METHODS: The Tc-99m HMPAO leukocyte scans of 37 patients with clinically suspected bone infection were reviewed. The patients were divided into two groups according to the presence of orthopedic implants. Early (4 to 6 hours) and delayed (18 to 20 hours) planar images and early SPECT images were obtained. The final diagnosis of infection was made based on the pathologic, bacteriologic, and surgical data and clinical follow-up. RESULTS: Group 1 (25 patients with orthopedic implants) included 15 true-positive, 1 false-negative, 7 true-negative, and 2 false-positive results. Group 2 (12 patients without orthopedic implants) included 7 true-positive, 1 false-negative, and 4 true-negative results. The overall sensitivity of the Tc-99m HMPAO leukocyte scan with SPECT to detect bone infection was 92%, with a specificity rate of 85%. (Group 1: sensitivity, 94%; specificity, 78%. Group 2: 88% and 100% sensitivity and specificity, respectively.) CONCLUSION: The Tc-99m HMPAO leukocyte scan is useful in the diagnosis of bone infection, regardless of the presence of orthopedic implants. The additional SPECT images may be helpful to localize the site of infection more accurately.

Adult↗

Accuracy and diagnostic sensitivity of radiographic absorptiometry of the second metacarpal.

The accuracy of a radiographic absorptiometry (RA) technique called digital image processing (DIP), discriminative ability of RA for osteoporotic fracture, and the relationship between RA and dual X-ray absorptiometry (DXA) of the spine and forearm were evaluated. We measured 16 cadaver hands, 32 healthy non-black premenopausal women, 39 healthy non-black postmenopausal women, and 35 non-black osteoporotic postmenopausal females. The overall correlation between the ash weights of the entire metacarpal and the DIP values was excellent (r = 0.954, P < 0.001, SEE = 0.14, CV = 6.4%). Short-term precision error of DIP was 3.5%. Age-related bone loss determined by DIP is comparable to that of spinal and forearm DXA: annual BMD decreases were 0.46% for DIP, 0.45% for forearm, and 0.32% for the spine. DIP of the 2nd metacarpal shows a gradient of risk for spinal fracture only slightly below that of forearm DXA, but substantially below that of spinal DXA. Age-adjusted odds ratios were 1.81 for RA, 2.45 for spinal DXA, and 1.94 for forearm DXA.

Absorptiometry, Photon↗

Diagnosis of orbital cavernous hemangioma with Tc-99m RBC SPECT.

The authors report two cases of orbital cavernous hemangioma diagnosed by Tc-99m RBC SPECT. Tc-99m RBC SPECT showed a typical scintigraphic pattern commonly seen in hepatic hemangioma in which there is intense focally increased uptake on delayed SPECT images. Tc-99m RBC SPECT in orbital cavernous hemangioma may be as useful a diagnostic modality as in hepatic hemangioma.

Adult↗

Imaging and quantitation of dopamine transporters with iodine-123-IPT in normal and Parkinson's disease subjects.

UNLABELLED: Iodine-123-N-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-( 4-chlorophenyl) tropane (123I-IPT) is a new dopamine transporter ligand that selectively binds the dopamine reuptake sites. Transporter concentrations have been known to decrease in Parkinson's disease patients. The purpose of this study was to evaluate the usefulness of IPT as an imaging agent for measuring changes in transporter concentrations in Parkinson's disease. METHODS: IPT labeled with 6.78 +/- 0.67 mCi 123I was injected intravenously as a bolus into eight normal controls (mean age 41 +/- 12 yr) and 17 Parkinson's disease patients (mean age 55 +/- 9 yr). Dynamic SPECT scans of the brain were then performed for 5 min each over 120 min on a triple-headed gamma camera equipped with medium-energy collimators. Regions of interest were drawn on the middle set of the image at the level of the basal ganglia (BG) for each subject. Time-activity curves were generated for the left BG, right BG and occipital cortex (OCC). The empirical ratios between BG-OCC and OCC, which represent specific-to-nonspecific binding ratios, were computed at various time points. The statistical parameter k3/k4 was estimated by two methods: a variation of the graphic method that derives the ratio of ligand distribution volumes (R[V]) and the area ratio method (R[A]), in which the ratio is calculated from the areas under the specific and nonspecific binding activity curves. RESULTS: The mean (BG-OCC)/OCC ratio for normal controls (3.07 +/- 0.73) was significantly higher than that for Parkinson's disease patients at 115 min (1.10 +/- 0.56) (p = 2.76 x 10[-5]). The mean R(V) and R(A) for normal controls were 2.06 +/- 0.27 and 1.50 +/- 0.15, respectively. The mean R(V) and R(A) for Parkinson's disease patients were 0.78 +/- 0.31 and 0.65 +/- 0.24, respectively. Both R(V) and R(A) for normal controls were significantly higher than those for Parkinson's disease patients (p values for R(V) and R(A) were 1.91 x 10(-8) and 3.46 x 10(-10), respectively). The R(V) has linear relationships with both R(A) and (BG-OCC)/OCC ratio at 115 min. The R(V) has a higher correlation (r = 0.99) with R(A) than it does with (BG-OCC)/OCC (r = 0.93). CONCLUSION: The R(V), R(A) and (BG-OCC)/OCC for Parkinson's disease patients were clearly separated from those of normal controls, and they may be useful outcome measures for clinical diagnosis. The simplest (BG-OCC)/OCC ratio, requiring a single late time point, could be useful in clinical situations, whereas R(V) or R(A) is preferred when the dynamic data are available. The findings suggest that 123I-IPT is a useful tracer for diagnosing Parkinson's disease and studying dopamine reuptake sites.

Adult↗

Stimulating technetium-99m cerebral perfusion studies with a three-dimensional Hoffmann brain phantom: collimator and filter selection in SPECT neuroimaging.

The choice of collimator and the selection of a filter can affect the quality of clinical SPECT images of the brain. The compromises that 4 different collimators make between spatial resolution and sensitivity were studied by imaging a three-dimensional Hoffmann brain phantom. The planar data were acquired with each collimator on a three-headed SPECT system and were reconstructed with both a standard Butterworth filter and a Wiener pre-filter. The reconstructed images were then evaluated by specialists in nuclear medicine and were also quantitatively analyzed with specific regions of interest (ROI) in the brain. All observers preferred the Wiener filter reconstructed images regardless of the collimator used to acquire the planar images. With this filter, the ultrahigh-resolution fan-beam collimator was the most subjectively preferable and quantitatively produced the highest contrast ratios. The findings support suggestions that higher resolution collimators are preferable to higher sensitivity collimators, and indicate that fan-beam collimators are preferable to parallel-hole collimators for clinical SPECT studies of cerebral perfusion. The results also suggest that Wiener filter enhances the quality of SPECT brain images regardless of which collimator is used to acquire the data.

Brain↗

Impact of childhood cancer on Korean families.

A health care system that includes institutions such as the home, clinic, or hospital as well as interpersonal relationships between providers and receivers of health care is a part of any culture. Clinical issues are a part of all cultures, and cross-cultural comparisons are useful in understanding health care. With immigration and travel, a better understanding of the situation of families who have a child with cancer in various countries, different health care systems, and different cultures is needed. Understanding the situation for families with a child who has cancer in South Korea will lead one to a better understanding of a Korean family who has immigrated to the west and has a child develop cancer or is in need of treatment.

Adolescent↗

Dual x-ray absorptiometry forearm software: accuracy and intermachine relationship.

An ash study was performed to analyze the accuracy of forearm measurements at the one-third site of three dual x-ray absorptiometry (DXA) systems using 20 cadavers. A Hologic QDR-2000, a Hologic QDR-1000/W, and a Lunar DPX-L system were used. The correlations between ash weight and DXA BMC were excellent for the three instruments (r > 0.97, p < 0.001), with accuracy errors < 5.2%. To perform a forearm cross-calibration of bone mineral content (BMC) and density (BMD) between the scanners, 10 healthy volunteers were additionally scanned at the distal one-third radius. The correlations among the DXA machines were excellent (r > 0.95); the absolute BMC and BMD values were significantly different between the two Hologics and the Lunar machine. The slope and intercept of both the BMC and BMD between the two Hologic systems were close to unity. In conclusion, the DXA forearm software packages provide accurate methods for assessing bone mineral content and density. The conversion of data among different manufacturers should be performed by careful cross-calibration measurements.

Absorptiometry, Photon↗

Radiographic absorptiometry for bone mineral measurement of the phalanges: precision and accuracy study.

PURPOSE: To evaluate the accuracy and precision of a radiographic absorptiometry (RA) method for assessment of bone mineral of the middle phalanges. MATERIALS AND METHODS: Nineteen cadaveric hands were radiographed with an aluminum wedge, once at 50 kVp and 400 mA and once at 60 kVp and 300 mA. Bone mineral content (BMC) and bone mineral density (BMD) of the second to fourth middle phalanges, expressed in arbitrary units (BMC-AU and BMD-AU), were analyzed and averaged in each hand. RESULTS: The precision error of this method was 1.0% for BMC-AU and 0.6% for BMD-AU. A 2.0%-2.4% reduction in BMD-AU seen on radiographs obtained through ethanol thicknesses of 5 and 6 mm compared with that seen on controls was statistically significant (P < .01). The correlation between BMC-AU and forearm BMC determined with dual x-ray absorptiometry was good (r = .887), and that between BMC-AU and ash weight in the phalanges was excellent (r = .983). CONCLUSION: The RA method is precise and accurate for bone mineral assessment of the peripheral appendicular skeleton.

Absorptiometry, Photon↗

Noninvasive bone mineral density measurement in the evaluation of osteoporosis.

Bone densitometry has developed considerably during the past several decades. Because the techniques have become more precise than before, osteoporotic patients can now be followed over time, allowing for assessment of disease or response to treatment. Several densitometry techniques have been shown to allow for the assessment of fracture risk. Factors other than density, however, additionally influence fracture risk. The next step will be the evaluation of microstructure and bone quality.

Aged↗

Pulmonary paragonimiasis: clinical and experimental studies.

Pulmonary paragonimiasis is a disease caused by a lung fluke. It is endemic to East Asia, but there have been several case reports in North America. Human infestation occurs by ingestion of raw or incompletely cooked freshwater crab or crayfish infected with metacercaria. A retrospective study was performed with 78 patients who lived in South Korea and had chest radiographic findings of pleuropulmonary disease; it was subsequently shown that they had paragonimiasis. The diagnosis was based on positive results of serologic tests for Paragonimus-specific antibody or on the detection of eggs in sputum samples. Radiologic findings from these 78 patients were correlated with the pathologic and radiologic findings from a study of experimentally induced pulmonary paragonimiasis in 21 cats. Findings from the correlative study document that the typical radiologic manifestations of pulmonary paragonimiasis vary with the stage of the disease. Early findings include pneumothorax or hydropneumothorax, focal airspace consolidation, and linear opacities and are caused by the migration of juvenile worms. Later findings include thin-walled cysts, dense masslike consolidation, nodules, or bronchiectasis and are due to worm cysts.

Adult↗

POEMS syndrome--a case report.

POEMS syndrome is a multisystem disorder associated with polyneuropathy, organomegaly, endocrinopathy, a monoclonal protein (M-protein), and skin changes. The authors describe a patient with POEMS syndrome who had osteosclerotic myeloma confirmed by open bone biopsy. Magnetic resonance imaging (MRI) showed discrete lesions of low signal intensity in both T1 and T2-weighted images. This patient is now being successfully treated with melphalan and prednisone with much improvement in skin thickening and sensory change in the lower extremities.

Adult↗

Detection of extrapulmonary tuberculosis with gallium-67 scan and computed tomography.

We evaluated 23 patients with extrapulmonary tuberculosis (TB) with 67Ga imaging to assess its usefulness in the diagnosis of this condition. We performed computed tomography (CT) in 17 patients to assess CT features of extrapulmonary TB in comparison with findings from 67Ga scans. Nineteen of 23 patients (83%) had positive findings on 67Ga scans. One of five patients with tuberculous mediastinal lymphadenopathy, two patients with cervical lymphadenitis and a patient with renal TB had negative 67Ga scans. It was observed that the detection of previously unrecognized primary foci of TB, without concomitant pulmonary TB, was possible using 67Ga imaging in five patients (22%). The 67Ga scan was relatively sensitive for the localization of extrapulmonary TB. It is suggested that the 67Ga scan could serve as a screening method, when followed by CT and ultrasonography, for the initial detection of occult tuberculous lesions, especially in patients with prolonged fever.

Adult↗

CT features of histiocytic medullary reticulosis.

Five cases of histiocytic medullary reticulosis (HMR) are presented and the computed tomographic (CT) findings described. All patients were young adults in their early twenties with fever, malaise and weight loss as their chief complaints. Survival was less than 5 months in all cases. The CT findings were hepatosplenomegaly (5), abdominal lymphadenopathy (5) and bilateral renal enlargement (2). Patchy low attenuation areas in the liver (2), wedge shaped splenic infarcts (2) and focal low attenuation areas in the kidneys (1) were also noted. Ascites (3) and pleural effusion (3) were associated findings.

Adult↗

Jejunal leiomyosarcoma detected by Tc-99m sulfur colloid gastrointestinal bleeding scan.

Jejunal leiomyosarcoma was initially detected in a patient by a gastrointestinal bleeding scan with Tc-99m sulfur colloid (SC). The scan showed increased blood flow and delayed persistent accumulation of radiotracer in the tumor. The Tc-99m SC gastrointestinal bleeding scan provided useful information to help determine the differential diagnosis of gastrointestinal tumor with bleeding.

Female↗