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Biomedical subjects

C K Kim

Publications and source records attributed to C K Kim.

At least 19 recordsLinked to original sources

Molecular cloning and characterization of catechol 2,3-dioxygenases from biphenyl/polychlorinated biphenyls-degrading bacteria.

Catechol 2,3-dioxygenases were cloned from Alcaligenes sp. KF711, Pseudomonas putida KF715, and Achromobacter xylosoxidans KF701 which are biphenyl/polychlorinated biphenyls-degrading bacteria. All of the cloned enzymes were purified by preparative polyacrylamide gel electrophoresis (PAGE). The purified catechol 2,3-dioxygenases were significantly different from one another in ring-fission activities to catechol and its derivatives. The catechol 2,3-dioxygenase from Alcaligenes sp. KF711 exhibited higher ring-fission activity to 4-chlorocatechol than those from P. putida KF715 and A. xylosoxidans KF701. In electrophoretic mobilities, the three enzymes were different from one another on nondenaturing PAGE but the same on SDS-PAGE.

Alcaligenes

Tolerance to the anticonvulsant effects of carbamazepine, diazepam, and sodium valproate in kindled rats.

We assessed the development of tolerance to the anticonvulsant effects of carbamazepine (CBZ), diazepam (DZP), and sodium valproate (VPA) on convulsions elicited by amygdala stimulation in kindled rats in three similar experiments. In each experiment, amygdala-kindled rats were assigned to a drug group or to a corresponding vehicle control group. The rats in the three drug groups received a total of 10 bidaily (one every 48 h) IP injections of CBZ (70 mg/kg), DZP (2 mg/kg) or VPA (250 mg/kg) at a dose that initially blocked the forelimb clonus elicited by an amygdala stimulation (400 microA, 60 Hz, 1 s) administered 1 h after the injection. The rats in the three vehicle control groups were similarly treated except that they received injections of the saline vehicle. The drug tolerance test occurred 48 h after the final tolerance-development trial; the rats from each drug group and the corresponding vehicle control group received an injection of the appropriate drug followed 1 h later by the administration of a convulsive stimulation. The drug tolerance test revealed almost total tolerance in each of the three drug groups but no tolerance in any of the three vehicle control groups. Such large tolerance effects are inconsistent with the less dramatic effects reported in previous studies; possible reasons for this inconsistency were considered.

Amygdala

Tolerance to the anticonvulsant effects of phenobarbital, trimethadione, and clonazepam in kindled rats: cross tolerance to carbamazepine.

The kindled-convulsion model was used to assess the development of tolerance and cross tolerance to the anticonvulsant effects of antiepileptic drugs. In Experiment 1, tolerance developed to the anticonvulsant effects of bidaily (one every 48 h) IP injections of phenobarbital, trimethadione, and clonazepam on convulsions elicited 1 h after each injection in kindled rats by amygdala stimulation. In Experiment 2, kindled rats that were tolerant to the anticonvulsant effects of phenobarbital, trimethadione, or clonazepam received bidaily IP injections of carbamazepine, each followed 1 h later by a convulsive amygdala stimulation. There was a statistically significant transfer of tolerance from phenobarbital to carbamazepine, but not from either trimethadione or clonazepam to carbamazepine. Apparently, tolerance to anticonvulsant drugs is most likely to transfer between drugs that are effective against similar kinds of clinical and experimental seizures and have similar putative mechanisms of action.

Amygdala

Contingent tolerance to the anticonvulsant effects of carbamazepine, diazepam, and sodium valproate in kindled rats.

The effect of convulsive stimulation during periods of drug exposure on the development of tolerance to the anticonvulsant effects of carbamazepine (CBZ), diazepam (DZP), or sodium valproate (VPA) was studied in three similar experiments. In each experiment, amygdala-kindled rats were assigned to one of three groups: one group received a drug injection (CBZ, 70 mg/kg, IP; DZP, 2 mg/kg, IP; VPA, 250 mg/kg, gavage) 1 h before each of a series of 10 bidaily (one every 48 h) convulsive stimulations, a second group received the same dose of the drug 1 h after each of the 10 stimulations, and a third group served as a vehicle control. The drug tolerance test occurred in each experiment 48 h after the 10th tolerance-development trial; every rat received the appropriate dose of CBZ, DZP, or VPA 1 h before being stimulated. In each experiment, only the rats from the drug-before-stimulation group displayed a significant amount of tolerance to the drug's anticonvulsant effect. Thus the development of tolerance to the anticonvulsant effects of CBZ, DZP, and VPA was not an inevitable consequence of drug exposure; the development of tolerance was contingent upon the occurrence of convulsive stimulation during the periods of drug exposure. These results support the idea that functional drug tolerance is an adaptation to a drug's effects on ongoing patterns of neural activity, rather than to drug exposure per se.

Amygdala

Bidirectional contingent cross tolerance between the anticonvulsant effects of pentobarbital and ethanol.

In Experiment 1, two groups of kindled rats received a pentobarbital injection (15 mg/kg, IP) and a convulsive amygdala stimulation once every 48 h. In one group, pentobarbital was injected 1 h before each stimulation; in the other, it was injected 1 h after each stimulation. Only the rats that received pentobarbital before each stimulation became tolerant to pentobarbital's anticonvulsant effect. Cross tolerance to the anticonvulsant effect of ethanol (1.5 g/kg, IP) was also found to be greater in the pentobarbital-before-stimulation rats. Experiment 2 was designed to assess the transfer of tolerance in the opposite direction, that is, from ethanol to pentobarbital, and the results mirrored those of Experiment 1: convulsive stimulation during the periods of ethanol exposure facilitated the development of tolerance to the anticonvulsant effect of ethanol and its transfer to pentobarbital. These results support the theory that functional drug tolerance and cross tolerance are adaptations to the effects of drugs on concurrent patterns of neural activity rather than to drug exposure per se.

Amygdala

Diagnosis of musculoskeletal infection using combined In-111 labeled leukocyte and Tc-99m SC marrow imaging.

Seventy-three patients with various underlying disorders that could potentially alter distribution of bone marrow underwent In-111 labeled autologous leukocyte and Tc-99m SC marrow imaging to exclude musculoskeletal infection. There were 22 cases of infection among the 73 patients studied. When interpreted in isolation, labeled leukocyte images were considered positive for infection when uptake of labeled cells in the region of interest exceeded uptake in the corresponding contralateral side. The sensitivity, specificity, and accuracy of the study using this criterion were 86%, 12%, and 34%, respectively. When interpreted in conjunction with sulfur colloid marrow images, studies were considered positive for infection when uptake in the region of interest on leukocyte and marrow images was spatially incongruent. The sensitivity, specificity, and accuracy of this dual tracer modality were 100%, 94%, and 96%, respectively. Three patients with infection and abnormal leukocyte/marrow images underwent repeat imaging after appropriate therapy. Images were interpreted as normal in two of them; both were infection free at subsequent surgery. Images of the third patient were interpreted as consistent with persistent infection, and operative cultures grew out Staphylococcus aureus. In summary, combined leukocyte/marrow imaging is a highly accurate method for diagnosing musculoskeletal infection and overcomes certain inherent limitations of labeled leukocyte imaging alone.

Adolescent

Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia.

The efficacy of antifolate, antiviral, and other drugs was compared in an experimental model of pneumocystosis. Sulfamethoxazole (SMX) administered alone in doses of greater than or equal to 60 mg/kg/day was highly effective in treatment and prophylaxis. Low (less than or equal to 15 mg/kg/day) doses of SMX showed limited, dose-related anti-Pneumocystis carinii activity in therapy but were more effective in prophylaxis. The dihydrofolate reductase (DHFR) inhibitors trimethoprim (TMP), pyrimethamine, and trimetrexate exhibited little anti-P. carinii activity when administered alone and did not enhance the efficacy of SMX; the effects of the DHFR inhibitors could not be related to the dose or the concentration in serum. These data suggested that the rat model is an excellent system for studying the anti-P. carinii activity of sulfonamides but is of limited value in studying DHFR inhibitors. The antiviral drugs azidothymidine, dideoxyinosine, inosine pranobex (Isoprinosine), amantadine, and acyclovir displayed little or no activity against P. carinii; however, azidothymidine did not impair the efficacy of SMX or TMP-SMX. These results supported the clinical practice of giving antiviral agents together with antifolate drugs to patients infected with human immunodeficiency virus and suggested that the beneficial effects of antiviral agents on the occurrence of pneumocystosis are due mainly to their effects on the virus or the host immune response. In contrast to the antiviral drugs, 9-deazainosine, a nucleoside analog with antiprotozoal properties, demonstrated marked activity against P. carinii which was related to dose and route of administration. These data raised the possibility that anti-P. carinii activity is a general property of purine nucleosides and suggested that further exploration of this class of compounds might lead to clinically useful agents.

Animals

Congenital absence of gallbladder.

Nine surgically proven congenital absence of gallbladder (CAGB) cases were reviewed. All of them had one or more kinds of biliary symptom. Tests such as abdominal ultrasonography, intravenous or oral cholecystography and even endoscopic retrograde cholangiography not only failed to predict CAGB but misleadingly indicated other similar conditions. Only the abdominal computed tomography (CT), performed on one patient, enabled the accurate diagnosis of CAGB. All the patients underwent abdominal exploration, and CAGB was confirmed by the meticulous dissection of the entire extrahepatic biliary tree and the operative cholangiography. Five patients had concomitant biliary pathologies responsible for their symptoms, but four patients had isolated CAGB. CAGB is a rarely encountered condition for a clinician, but extensive diagnostic work-ups including abdominal CT should be performed in all situations where CAGB is suspected. Thus unnecessary exploration can be avoided in the isolated CAGB case.

Bile Duct Diseases

New grading system of cerebral gliomas using positron emission tomography with F-18 fluorodeoxyglucose.

Positron emission tomography (PET) using fluorine-18 (18F)-fluorodeoxyglucose (FDG) has been reported to be a powerful diagnostic and prognostic tool in patients with primary brain tumors. This study was undertaken to compare the prognostic value of: (1) visual grading of [18]FDG uptake in the tumor, (2) the absolute glucose metabolic rate of the tumor (TMRglc), (3) the ratio of glucose metabolism between the tumor and whole brain (T/WB) and (4) between the tumor and contralateral cerebellum (T/CBL). Each of these four parameters was correlated with the survival time in 20 patients with malignant cerebral gliomas. Excellent correlation was obtained with visual grading and reasonably good correlation was obtained with T/WB or T/CBL, but TMRglc alone was only a fair prognostic indicator. Thus, visual grading provides a qualitative analysis and T/WB provides a semi-quantitative analysis neither of which requires arterial blood sampling for quantification of absolute metabolic rates for glucose.

Brain Neoplasms

Role of in-111 labeled leukocyte scintigraphy in the diagnosis of intracerebral lesions.

The differential diagnosis of intracerebral enhancing lesions on contrast computed tomography includes tumors, abscesses, and cerebrovascular accidents. Particularly important is the differentiation between tumor and abscess. While In-111 labeled leukocyte imaging is an accurate test for identification of foci of infection in general, the role of this procedure in the evaluation of the intracranial lesion is not well established. We undertook a retrospective review of 16 patients with contrast enhancing intracerebral lesions identified on computed tomography, who were also studied with labeled leukocyte imaging. Final diagnoses were: abscess (n = 2), primary brain tumor (n = 6), metastasis (n = 4), dermoid cyst (n = 1), and cerebral infarct (n = 3). There were two positive labeled leukocyte studies; both were cerebral abscesses. No labeled leukocyte activity was identified in any of the tumors or infarcts. We conclude that In-111 labeled leukocyte imaging is an accurate method of differentiating infectious from noninfectious causes of intracerebral lesions identified on computed tomography.

Adult

Furazolidone and nitrofurantoin in the treatment of experimental Pneumocystis carinii pneumonia.

Furazolidone and nitrofurantoin, oral nitrofuran derivatives with broad-spectrum antimicrobial properties already in clinical use, were compared for activity against Pneumocystis carinii in an immunosuppressed rat model of P. carinii pneumonia. Furazolidone exhibited only slight activity as a prophylactic agent but was moderately effective in the therapy of pneumocystosis. The median histologic score and organism count fell from 4+ and 10(8) to 10(9) cysts per lung, respectively, in the controls to 1+ to 2+ and 10(7) to 10(8) cysts per lung, respectively, in the furazolidone-treated groups. However, these results were not as good as those obtained with the standard drug, trimethoprim-sulfamethoxazole (0+, 10(6) to 10(7) cysts per lung). Nitrofurantoin showed little anti-P. carinii activity despite different doses or drug preparations. The high doses of furazolidone used here and their toxic effects on the rats will probably discourage investigation of this drug in the treatment of pneumocystosis in humans. Nevertheless, since many nitrofurans have been synthesized, further exploration of this class of compounds might be helpful in developing new anti-P. carinii agents or in studying structure-activity relationships.

Animals