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Biomedical subjects

C H Park

Publications and source records attributed to C H Park.

At least 19 recordsLinked to original sources

Is there etiologic heterogeneity between upper and lower neural tube defects?

Neural tube defects are thought to arise from two different embryologic mechanisms depending on the level of the defect: neurulation defects associated with anencephaly and upper spina bifida and canalization defects associated with lower spina bifida. To investigate whether the risk profiles of neural tube defect cases differ according to the level of the defect, the authors examined data from the Atlanta Birth Defects Case-Control Study. Cases were infants live- or stillborn from 1968 to 1980 with these defects, and controls were infants without defects randomly selected and frequency matched to cases by race, birth year, and hospital of birth. By multivariate polychotomous logistic regression, 1,186 controls were compared with cases: 145 with anencephaly, 59 with upper spina bifida (cervical/thoracic lesions), and 100 with lower spina bifida (lumbar/sacral lesions). Infant's sex and sibling recurrence of neural tube defects were the only factors for which the case subgroups significantly differed in risk. The risks associated with selected maternal exposures during the first trimester of pregnancy did not differ among the case subgroups. Although these results do not support the concept that upper and lower neural tube defects differ in risks from exogenous factors, differences in sibling recurrence and in risks by sex between the two groups suggest an underlying heterogeneity in genetic susceptibility factors.

Anencephaly

In vitro growth modulation by L-ascorbic acid of colony-forming cells from bone marrow of patients with myelodysplastic syndromes.

In vitro colony growth was studied on bone marrow cells from 51 patients with myelodysplastic syndromes (MDS), using a cell culture method with the unique feature of daily feeding, in an effort to gain insight into the pathophysiology of MDS and to assess the clinical utility of this cell culture assay. The colony growth pattern of MDS marrow cells is remarkably similar to that of acute myeloid leukemia but quite dissimilar from that of normal marrow, in support of a common pathophysiological mechanism for these two disorders. In particular, L-ascorbic acid (LAA) enhanced colony growth in 30% and suppressed growth in 16% of cases, a finding also similar to that in acute myeloid leukemia, indicating a unique growth requirement which may be explored for therapeutic purposes. Further, these LAA effects have prognostic value, with LAA-sensitive (both LAA-enhanced and LAA-suppressed) cases displaying shorter survivals than LAA-insensitive cases (median survival of 5 months versus 18 months; P = 0.011). This prognostic value is independent of, and more powerful than, bone marrow blasts; the median survival was 18 months for less than 5% bone marrow blasts and 8 months for greater than 5% bone marrow blasts (P = 0.044). These two risk factors can be used together to identify patients with an extremely good or an extremely poor prognosis. This study establishes the clinical usefulness of the LAA effect in MDS as a prognostic factor and provides a new lead to explore in understanding differential biochemical/molecular events and, possibly, a new therapeutic approach to the management of MDS.

Adolescent

Structure of a pepsin/renin inhibitor complex reveals a novel crystal packing induced by minor chemical alterations in the inhibitor.

The structure determination by molecular replacement methods of a monoclinic pepsin/renin inhibitor complex crystal, with two molecules in the asymmetric unit, is presented. The atomic model, consisting of two liganded pepsin molecules and 110 water molecules, has been refined to a final crystallographic R value of 0.139 for data between 8 and 2.9 A resolution. The structure reveals a previously undescribed pepsin dimer formed predominantly by polar interactions. Inhibitor binding induces global structural changes in the native enzyme similar, but not identical, to the ones observed in other chemically similar pepsin/renin inhibitor complexes crystallized in an orthorhombic form. A region of the polypeptide chain (residues 292-297) which was not visible in the orthorhombic crystal is well ordered in the presently described structure; possibly induced by crystal contacts. The crystal packing of native pepsin is compared with the two different crystal forms of the inhibited enzyme.

Binding Sites

Antibacterials. synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 4. Multiply-substituted aryl derivatives.

The synthesis and structure-activity relationship (SAR) studies of the effect of different polysubstitution patterns in the aromatic ring of 5-(acetamidomethyl)oxazolidinone antibacterials (I) on antibacterial activity are presented. Compounds I were prepared by the six-step synthesis described previously (Gregory, W. A.; et al. J. Med. Chem. [formula: see text] 1989, 32, 1673), electrophilic aromatic substitution reactions of 3-substituted compounds, and functional-group interchange reactions of 3,4-disubstituted compounds. Antibacterial evaluation of compounds I against Staphylococcus aureus and Enterococcus faecalis gave the following results. The 2,4- and 2,5-disubstituted derivatives have weak or no antibacterial activity. Antibacterial activities of 3,4-disubstituted compounds are comparable to those of the 4-monosubstituted analogues for small 3-substituents (smaller than Br), but decline rapidly for larger 3-substituents. 3,4-Annulated derivatives are comparable in activity to their open-chain analogues. 3,5-Disubstituted and 3,4,5- and 2,4,6-trisubstituted derivatives are devoid of antibacterial activity.

Anti-Bacterial Agents

Reduction of flurazepam's antiseizure efficacy persists after stress.

Twenty-four hours after mice were forced to swim for up to 10 min in cold (6 degrees C) water, the ability of flurazepam to antagonize the electrical precipitation of seizures was reduced. This stress-induced reduction in flurazepam's antiseizure efficacy persisted for at least 72 h; but was absent 1 week after the single session of swim stress. The data may be relevant to stress-related psychiatric disorders and suggest that the therapeutic efficacy of benzodiazepines may be altered after a severe stress.

Animals

Mass-like hepatic hypertrophy: MRI findings with histologic correlation.

Hepatic parenchyma may hypertrophy following asymmetrical injury. The histologic characteristics of hypertrophic hepatic parenchyma are more similar to normal hepatic parenchyma than is the more severely damaged liver. We present four cases where large hypertrophic masses resembled neoplasm on other imaging modalities or at surgery, but had MRI signal characteristics similar to those of normal liver.

Adult

Nonpustular psoriatic lesions detected by Tc-99m HMPAO labeled granulocytes.

A patient with a fever of unknown origin was evaluated by abdominal SPECT using Tc-99m HMPAO labeled granulocytes and a triple detector camera. Although no abscesses were located, nonpustular psoriatic skin lesions were demonstrated incidentally on the reprojectional images. Psoriatic scales contain a chemotactic factor for leukocytes, and this is a likely explanation for the increased uptake of the radiotracer by psoriatic lesions.

Fever of Unknown Origin

Dual isotope SPECT in the evaluation of recurrent brain tumor.

Dual isotope brain SPECT was performed in a patient with recurrent brain tumor (grade II astrocytoma). In this case, a good coregistration of brain perfusion and tumor images was obtained because Tc-99m HMPAO and the Tl-201 chloride imaging were done simultaneously using a Triad SPECT unit. This method might play an important clinical role in the evaluation of patients with recurrent brain tumors.

Adult

Reverse crossed cerebellar diaschisis in partial complex seizures related to herpes simplex encephalitis.

Tc-99m HMPAO brain SPECT was performed in a patient who had partial complex seizures for 1 year after successful acyclovir treatment of biopsy-proven herpes simplex encephalitis 2 years earlier. In spite of antiepileptic medications, her seizures were intractable and occurred daily. Tc-99m HMPAO was administered intravenously while she was having subclinical seizures, and brain SPECT demonstrated an area of hyperperfusion in the right temporal lobe medially and in the contralateral cerebellum. This reverse of the crossed cerebellar diaschisis phenomenon in epileptic disorders has not previously been documented.

Adult

Tc-99m DTPA diffuse pulmonary uptake in patients with coronary artery disease and renal insufficiency.

Diffuse bilateral lung uptake was observed in 10 patients undergoing Tc-99m DTPA renal scanning, referred for the evaluation of rising serum creatinine levels. All 10 patients demonstrated renal insufficiency (RI) as shown by both decreased bilateral renal tracer concentration and elevated background activity. Nine of the patients were known to have coronary artery disease (CAD) and six of these nine patients were in congestive heart failure (CHF), at or around the time of scanning. However, Tc-99m DTPA lung uptake was not observed in five other patients whose scans demonstrated RI, in whom there was no CAD or other cardiac disease. Diffuse lung uptake of Tc-99m DTPA in patients with RI therefore is highly suggestive of cardiac dysfunction (i.e. CAD and/or CHF).

Aged

Primary pontine hemorrhage: a new CT classification.

The prognosis of primary pontine hemorrhage depends on the size, location, and extent of the hematoma. We investigated the relationship between CT features and prognosis in 61 consecutive cases. The CT features were classified into four types: basal-tegmental (23 cases), bilateral tegmental (7), massive (14), and small unilateral tegmental (17). Case survival rate was 94.1% for the small unilateral tegmental type, 26.1% for the basal-tegmental type, 14.3% for the bilateral tegmental type, and 7.1% for the massive type.

Adolescent

Brain SPECT in neonates following extracorporeal membrane oxygenation: evaluation of technique and preliminary results.

Extracorporeal membrane oxygenation (ECMO) is a life-saving procedure in neonates with refractory respiratory failure that has been used at our institution since 1985. In an attempt to study its clinical value, regional cerebral blood flow (rCBF) alterations were measured using SPECT and 99mTc-HMPAO in 13 newborns following ECMO. Eight infants were studied after ECMO with reanastomosis of the right common carotid artery (RCCA), two with the permanent ligation of the RCCA, and three after veno-venous ECMO. Brain SPECT was technically satisfactory in all newborns using a triple-head SPECT system. Altered rCBF was found in 7 of 13 infants. In five newborns, there was a decrease in rCBF within the ipsilateral hemisphere, and in one infant, contralateral hemisphere was involved. In one infant, there was bilateral hemispheric involvement. The infant underwent cardiopulmonary resuscitation prior to ECMO and exhibited clinical features of hypoxicischemic encephalopathy at the time of SPECT. Only 2 of 13 newborns demonstrated morphologic changes on neuroimaging modalities such as cranial ultrasonography, computed tomography and magnetic resonance imaging. Our study demonstrates that: (1) functional brain imaging is feasible in neonates after ECMO; (2) SPECT has potential for demonstrating rCBF deficits not detectable by neuroanatomic imaging modalities; and (3) SPECT has potential clinical value in long-term follow-up of neurodevelopmental outcome after ECMO.

Brain

Gallium-67 scintiscan in the diagnosis of primary splenic non-Hodgkin's lymphoma after the treatment of Hodgkin's disease.

A rare primary non-Hodgkin's lymphoma (diffuse large cell) of the spleen developed in a 72-yr-old man who had successful radiotherapy to the right inguinal region for Hodgkin's disease 23 yr ago. Radiologic findings, particularly the 67Ga scintigraphy finding, were very useful in leading to the correct diagnosis of malignant splenic lymphoma, in this case, preoperatively.

Aged

The effect of granulocyte-macrophage colony-stimulating factor on undifferentiated and mature acute myelogenous leukemia blast progenitors.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used recently to recruit undifferentiated acute myelogenous leukemia (AML) blasts into the S-phase of the cell cycle and increase the fraction of cells killed by cell cycle-specific drugs. Using three AML blast colony assays combined with a suspension culture (delta assay), we determined the in vitro effect of GM-CSF on mature and undifferentiated AML blast progenitors obtained from bone marrow aspirates of six AML patients. GM-CSF stimulated AML blast colony proliferation at a concentration of 5 ng/ml in the methylcellulose and the agar clonogenic assays in six of six AML marrow samples. However, in the delta assay, which selects for immature AML progenitors, GM-CSF did not affect AML blast colony-forming cells in five of six AML marrow samples at concentrations ranging from 5 to 300 ng/ml. Our data imply that GM-CSF stimulates mature but not undifferentiated AML blast progenitors. It is therefore possible that GM-CSF may not be beneficial as a recruiting agent in most AML patients.

Adult

Successful therapy of crystalcryoglobulinemia: a case report.

Successful therapy for a case of multiple myeloma with a spontaneously crystallizing cryoglobulin of the IgG2-kappa light chain variety was achieved, using both continuous-flow cell centrifugation plasmapheresis to rapidly lower the M component and combination chemotherapy with phenylalanine mustard, prednisone, procarbazine, and vincristine to control the myeloma process. This resulted in resolution of incapacitating large and small necrotic cutaneous ulcerations of the extremities. Physicochemical studies of the crystalcryoprotein demonstrated that cryoprecipitation was rapid and accompanied by the formation of needle-shaped crystals, yet was completely reversible at 37 degrees C. Cryocrit determinations varied depending upon relative centrifugal forces and temperature and did not always relate linearly to the amount of abnormal protein, thus making these alone unreliable in assessing response to therapy.

Antineoplastic Agents