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Biomedical subjects

J K Roh

Publications and source records attributed to J K Roh.

At least 91 records · Page 5Linked to original sources

Inhibitory effects of H2-receptor antagonists on cytochrome P450 in male ICR mice.

1. The present study was undertaken to examine the effects of H2-receptor antagonists including newly developed mifentidine derivatives, IY-80843 and IY-80845, on cytochrome P450(P450) in vitro and in vivo. 2. Initially, 3-methylcholanthrene-, phenobarbital-, ethanol- and dexamethasone-induced liver microsomes were prepared from male ICR mice to study in vitro effects of above chemicals on ethoxyresorufin O-deethylase(EROD), pentoxyresorufin O-dealkylase(PROD), p-nitrophenol hydroxylase and erythromycin N-demethylase(ERDM) activities, respectively. It was found that histamine, cimetidine and famotidine were not inhibitory to four enzyme activities. Meanwhile, mifentidine slightly inhibited EROD and PROD activities and its derivatives IY-80843 and IY-80845 strongly inhibited PROD, EROD and ERDM activities. 3. Prolongation of hexobarbital-induced sleeping time was determined in male ICR mice to confirm in vitro inhibitory effects of mifentidine and its derivatives in vivo. It was observed that cimetidine, mifentidine, IY-80843 and IY-80845 caused dose-dependent increases in the sleeping time, indicating the inhibition of P450 responsible for hexobarbital metabolism. 4. It was concluded that mifentidine and its derivatives are P450 inhibitors and that our newly synthesized IY-80843 is most inhibitory. 5. The present results indicate that mifentidine and its derivatives not only antagonise the H2-receptor but also inhibit P450 enzymes.

Amidines↗

Cerebral venous thrombosis associated with maxillary and ethmoid sinusitis--a case report.

We herein report a young patient with cerebral venous thrombosis (CVT) with clinical and neuroradiological findings of the left maxillary and anterior ethmoid sinusitis. Serial brain MRIs showed cerebral venous infarct and thrombosis in the superior sagittal sinus (SSS). MR angiography demonstrated nonvisualization of SSS and bilateral transverse sinus. According to our knowledge, CVT associated with maxillary and ethmoid sinusitis has been reported very rarely. High index of suspicion and neuroimaging studies, especially brain MRI, and conventional or MR angiography are very important for the early diagnosis of CVT.

Adult↗

Chemopreventive effect of green tea (Camellia sinensis) among cigarette smokers.

Chemopreventive effects of green tea and coffee among cigarette smokers were examined in 52 clinically healthy male subjects between 20 and 52 years of age. Blood specimens were obtained from nonsmokers (group I), smokers (group II), smokers consuming green tea (group III), and smokers drinking coffee (group IV). The mean number of cigarette smoking years (> 10 cigarettes/day) in groups II-IV ranged from 13.4 to 14.7 years. Daily intake of green tea and coffee was 2-3 cups/day for 6 months (groups III and IV). The frequencies of sisterchromatid exchange (SCE) in mitogen-stimulated peripheral lymphocytes from each experimental group were determined and analyzed statistically. SCE rates were elevated significantly in smokers (9.46 +/- 0.46) versus nonsmokers (7.03 +/- 0.33); however, the frequency of SCE in smokers who consumed green tea (7.94 +/- 0.31) was comparable to that of nonsmokers, implying that green tea can block the cigarette-induced increase in SCE frequency. Coffee, in contrast, did not exhibit a significant inhibitory effect on smoking-induced SCE.

Adult↗

The role of radiation treatment in management of extrahepatic biliary tract metastasis from gastric carcinoma.

PURPOSE: To determine the proper role of radiation treatment in the management of patients with extrahepatic biliary tract metastasis due to recurrent gastric cancer. METHODS AND MATERIALS: Twenty patients with malignant biliary obstruction due to recurrent gastric carcinoma after gastrectomy were treated with palliative intent at the Yonsei University College of Medicine from 1986 to 1990. Treatment consisted of external drainage alone in 11 patients (Group I) and external drainage followed by radiation treatment in nine patients (Group II). Five of nine patients in Group II underwent external irradiation in combination with intraluminal brachytherapy using high dose rate Iridium-192 (Ir-192) sources within the expandable intrabiliary prosthesis, a Gianturco stent, inserted transhepatically at the site of obstruction. RESULTS: An excellent local response was observed in five of nine patients in Group II, in whom biliary patency was restored following treatment so that the external drainage catheter could be removed. Prolongation of median survival was observed in Group II (9 months) as compared to Group I (2 months). There were no serious treatment-related complications with this approach. CONCLUSION: This treatment approach with external radiotherapy +/- intraluminal brachytherapy could achieve effective palliation and improve the quality of life in selected patients with extrahepatic biliary metastasis from gastric carcinoma.

Adult↗

Changing trends in histologic types of lung cancer during the last decade (1981-1990) in Korea: a hospital-based study.

A review of the histopathology and past history of 2229 patients with primary lung cancer diagnosed at the Yonsei University Medical Center from 1981 to 1990 was performed to investigate the changes in histologic types and the relationship to smoking history. The most frequent histologic type of lung cancer was squamous cell carcinoma (956 patients, 54.0%) followed by adenocarcinoma (311 patients, 17.6%) in males (1772 patients), and adenocarcinoma (206 patients, 45.1%) followed by squamous cell carcinoma (126 patients, 27.6%) in females (457 patients). In both sexes, the predominant type was adenocarcinoma under the age of 40, whereas squamous cell carcinoma was the most frequent type above the age of 40. While squamous cell carcinoma decreased over 10 years (54.3% in 1981, 44.3% in 1990), adenocarcinoma showed a gradually increased incidence (17.0% in 1981, 28.3% in 1990) in both sexes, and the proportion of small cell carcinoma and large cell carcinoma remained unchanged. These changes in histologic type were more prominent in non-smokers. In conclusion, the increasing incidence of adenocarcinoma in both sexes, especially in non-smokers, suggests the possible presence of etiologic factors other than smoking, such as environmental pollution.

Adolescent↗

Initial and follow-up brain MRI findings and correlation with the clinical course in Wilson's disease.

We performed pretreatment brain MRIs in 25 patients with neurologically symptomatic Wilson's disease (WD) and clinical and MRI follow-up in 16 of them. All 25 pretreatment MRIs revealed abnormalities, with abnormal high-signal intensity (HSI) in bilateral thalami being the most common (92%). HSI lesions in the brainstem (84%) and the basal ganglia (72%) were also common. Brain atrophy was present in 88% of the 25 patients. In the follow-up period of 5 to 24 months, during which the patients were treated with D-penicillamine, both HSI lesions and neurologic symptoms improved in 88% of the 16 patients, but the brain atrophy did not change.

Adolescent↗

A clinical study of benign focal amyotrophy.

We reviewed the clinical, electrophysiological, radiological, and histopathological findings in 25 patients with benign focal amyotrophy. There were 14 patients with upper limb type and 11 with lower limb type. 18 patients had unilateral involvement and 7 had bilateral involvement asymmetrically. The characteristics clinical features were sporadic occurrence, predominance in young males, nonprogressive course or initial progression for 1 to 3 years followed by stationary state, segmental distribution of muscle weakness and atrophy localized to one limb or both homologous limbs markedly asymmetrically, and absence of any definite sensory loss or central nervous system involvement. The electrophysiological, radiological, and muscle histopathological findings suggested chronic focal anterior horn cell disease. Although the prevalence of this disease is still unknown, the importance of recognition is being emphasized because of its common occurrence in our country and the benign prognosis.

Adolescent↗

Amnesia syndrome following left anterior thalamic infarction; with intrahemispheric and crossed cerebro-cerebellar diaschisis on brain SPECT.

We report a 61-year-old right-handed man developing disturbance of memory after a discrete thalamic infarction. Neuropsychological assessment revealed deficits in memory with retrograde and anterograde components, especially for verbal material. Brain MRI showed a left anterior thalamic infarction with normal angiographic findings. Despite the small lesion in the thalamus, he showed prolonged memory disturbance and a Brain SPECT image revealed decreased uptake in the ipsilateral fronto-temporo-parietal cortex and contralateral cerebellum. This diaschisis, a phenomenon caused by disconnection of the neural pathway helped us to evaluate the functional state of the patient and this imaging technique was valuable for obtaining to get more information for the evaluation of the neurological state and neuronal connections. In conclusion our findings correspond well with the understanding of amnesia as a disconnection syndrome because of the evidence of diaschisis on the Brain SPECT image.

Amnesia↗

Clastogenicity of methapyrilene hydrochloride in cultured Chinese hamster cells.

The antihistaminic agent methapyrilene hydrochloride (MPH, CAS No. 135-23-9) has been reported as a potent rat hepatocarcinogen. However, neither the action mechanism nor mutagenicity of MPH have been clearly elucidated yet. Chromosomal aberration (CA) tests were performed with MPH in CHO-K1-BH4 and CHL cells without a metabolic activation system. Isochromatid break-like aberrations were observed in metaphases of CHO-K1-BH4 cells treated with MPH. MPH induced CA more effectively at higher pH in equitoxicity base. In contrast to CHO-K1-BH4 cells, typical chromatid type exchanges were observed in CHL cells treated with MPH. These results clearly support the results of other researchers that MPH induce chromosomal aberration and imply that MPH induces cancer in animal via other mechanisms than mere DNA damage or gene mutation which had been nearly proven to be negative by many researchers. It was suggested that pH variation might increase the sensitivity of CA tests for certain category of chemicals with dissociation potential.

Animals↗

Teratogenicity study of Scutellariae Radix in rats.

This teratogenicity study was carried out in pregnant S.P.F. Sprague-Dawley female rats. These animals received for a period of 11 days, from day 7 to 17 of gestation, by daily oral administration, the water extract concentrates of the medicinal herb, Scutellariae Radix, at dose levels of 0.25 g/kg (group I), 12.49 g/kg (group II), and 24.98 g/kg (group III). Two-thirds of pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and postnatal development of the offspring was observed. There was a significant (P < 0.05) dose-dependent increase in the incidence of skeletal variations (presence of lumbar rib). There was also a dose-dependent increase in the incidence of abnormal urinary system (mainly dilatation of ureter) although the abnormality incidence of group III was comparable to group II. There were no significant differences between the control and treated groups in maternal body weight, intake of diet and water, efficiency of diet, hematologic values, resorbed and dead fetuses, corpora lutea, separation of eyelids, emergence of abdominal hair and incisors, traction test values, sex organ function in fetuses, and growth of fetuses.

Abnormalities, Drug-Induced↗

Comparative nephrotoxicity of tetraplatin and cisplatin in rats.

Cisplatin, a useful therapeutic agent against many forms of cancer, possesses significant nephrotoxicity, necessitating a search for agents with similar therapeutic profiles but with less potential for renal damage. Since tetraplatin, another platinum analog being evaluated in phase I clinical trials, has a favorable therapeutic profile when compared to cisplatin, we examined the comparative nephrotoxicity of tetraplatin and cisplatin in rats when both compounds were administered at equimolar doses. Based on various parameters, we found that tetraplatin was less nephrotoxic. In vivo injections of equimolar doses of tetraplatin caused a much lesser rise in serum urea nitrogen and creatinine when compared to cisplatin. In vitro, renal slice accumulation of 3H-p-aminohippurate and 14C-tetraethylammonium was significantly decreased after cisplatin but not after tetraplatin. Morphological damage in the kidneys was more severe after cisplatin compared to tetraplatin. We conclude through in vivo and in vitro methodology that tetraplatin is significantly less nephrotoxic than cisplatin at comparable therapeutic doses.

Animals↗

Teratogenicity study (segment II) of recombinant granulocyte-macrophage colony stimulating factors (LBD-005) in rats.

A teratogenicity study was carried out in Sprague-Dawley rats subcutaneously injected recombinant Granulocyte-Macrophage Colony Stimulating Factors (LBD-005), the growth of stem cell and the development of the hematopoietic cell, at dose levels of 250, 500 and 1000 micrograms/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the offspring was observed. The incidences of external, internal and skeletal anomalies were not significantly increased in the fetuses of any treated groups. Recombinant GM-CSF caused no effects on parturition, lactation, postnatal growth and reproductive ability of the male and female offsprings.

Abnormalities, Drug-Induced↗

Peri- and postnatal study (segment III) of recombinant granulocyte-macrophage colony stimulating factors (LBD-005) in rats.

A perinatal and postnatal study was carried out in Sprague-Dawley rats subcutaneously injected recombinant Granulocyte-Macrophage Colony Stimulating Factors (LBD-005), the growth of stem cell and the development of the hematopoietic cell, at dose levels of 250, 500 and 1000 micrograms/kg/day for a period from day 17 of gestation to day 21 after delivery. All pregnant dams were allowed to litter naturally, and the postnatal development of the offsprings was observed. The incidences of external, internal and skeletal anomalies were not significantly increased in the F1 and F2 fetuses of any treated groups. Recombinant GM-CSF caused no effects on parturition, lactation, postnatal growth and differentiation, behaviour and reproductive ability of the male and female offsprings.

Animals↗

An acute toxicity study of recombinant human interferon alpha A (LBD-007) in Sprague-Dawley rats.

The acute toxicity of a recombinant human interferon alpha A (code name: LBD-007) was evaluated in both sexes of Sprague-Dawley rats, 5 weeks old, by the oral, subcutaneous and intravenous routes of administration. Based on the results, LBD-007 was not considered to induce any toxicological effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD50 values in rats would be > 48 x 10(8) IU/kg in the study of oral administration and > 24 x 10(8) IU/kg in the study of subcutaneous or intravenous administration.

Administration, Oral↗

A 4-week subcutaneous toxicity study of recombinant human interferon alpha A (LBD-007) in Sprague-Dawley rats.

Recombinant human interferon alpha A (code name: LBD-007) was subcutaneously administered to both sexes of Sprague-Dawley rats at the doses of 0, 6, 12 and 24 x 10(6) IU/kg of body weight five days per week for 4 weeks to evaluate the subchronic toxicity. 20 to 50% of rats except the male control group showed minimal to mild, focal to multifocal renal mineralization. Whether renal mineralization is related to the test substance is not elucidated. Male rats dosed at 24 x 10(6) IU/kg showed the decrease of the absolute kidney weights and the increase of the brain relative weights. Female rats dosed at 24 x 10(6) IU/kg showed the increase of the absolute and relative ovary weights, and the decreases of specific gravity, bilirubin and urobilinogen in urine. However, no drug-related changes were noted in clinical findings, body weights, food consumption, water consumption, hematology, blood clinical chemistry and necropsy findings. Based on the results it is concluded that the estimated subcutaneous non-toxic dose of the recombinant human interferon alpha A (LBD-007) in rats is (6 approximately 12) x 10(6) IU/kg.

Animals↗

A 6-month subcutaneous toxicity study of recombinant human interferon alpha A (LBD-007) in Sprague-Dawley rats.

Recombinant human interferon alpha A (code name: LBD-007) was subcutaneously administered to both sexes of Sprague-Dawley rats at the doses of 0, 3, 6 and 12 x 10(6) IU/kg of body weight six days per week for 6 months to evaluate the chronic toxicity. Male rats dosed at 12 x 10(6) IU/kg for 26 weeks showed a decrease of ketone body in the urine, and female rats dosed at 12 x 10(6) IU/kg for 26 weeks showed a decrease of serum alkaline phosphatase. Microscopic changes with remarkable incidence were nephropathy, renal mineralization and ultimobranchial cysts of the thyroid gland in all groups of both sexes of rats. These changes were not considered to be drug-related toxicity because they appeared to be minimal, occasionally mild in severity and did not have dose-dependency as well as clinical significance. In general, no drug-related change was noted in clinical findings, body weights, food consumption, water consumption, hematology, organ weights and necropsy findings. Based on the results, it is concluded that the estimated subcutaneous non-toxic dose of the recombinant human interferon alpha A (LBD-007) in rats would be 6 x 10(6) IU/kg.

Alkaline Phosphatase↗

A study on antigenicity of recombinant human interferon alpha A (LBD-007) in mice and guinea pigs.

Antigenicity of recombinant human interferon alpha A (LBD-007), a newly developed drug for myeloid leukemia and hepatitis, was investigated in mice and guinea pigs. The following results were obtained: 1. Mice showed no production of antibodies against LBD-007 inoculated with aluminum hydroxide gel (alum) as an adjuvant, judged by the heterologous anaphylaxis (PCA) test using rats. On the other hand, antibodies against ovalbumin (OVA) inoculated with alum were definitely detected. 2. In the studies with guinea pigs, both the inoculation of LBD-007 only and of LBD-007 with complete Freund's adjuvant (CFA) as an adjuvant did not produce positive reactions in any of homologous active systemic anaphylaxis (ASA). On the other hand, the inoculation of ovalbumin with complete Freund's adjuvant (CFA) produced positive reaction in both of PCA and ASA. 3. These findings suggested that LBD-007 has no antigenic potential in mice or guinea pigs.

Anaphylaxis↗

Comparison of p53 gene mutations in paired primary and metastatic gastric tumor tissues.

Our previous study revealed that mutations of the p53 gene were detected by cDNA sequencing in one of four (25%) primary gastric tumors and in five of six (83%) gastric cancer cell lines. It was of interest that all five cell lines established from metastatic lesions had p53 gene mutations, while the single cell line established from a primary tumor lacked an abnormality. Thus, the current study was initiated to determine the frequency of p53 mutations in 10 pairs of samples from primary gastric carcinomas and their lymph node metastases, in addition to morphologically normal gastric mucosa. In addition, we correlated the findings with other relevant molecular markers including the metastasis associated nm23-H1 gene and loss of heterozygosity (LOH) using multiple polymorphic markers for chromosome 17p and sequencing the entire open reading frame (ORF) of the p53 gene. Five of ten (50%) patients were constitutionally heterozygous for one or more 17p and/or p53 probes (pYNZ 22, BamHI RFLP; pMct35.1, Mspl RFLP; php53cl, Bg/II RFLP), while none had LOH at the 17p and/or p53. A Bg/II RFLP for analysis of possible nm23-H1 somatic allelic deletion revealed no LOH out of four informative cases. One paired sample demonstrated the substitution of valine for isoleucine at codon 41 (GTT to ATT) in both primary gastric tumor and metastasis. Another metastatic sample demonstrated the substitution of proline for threonine at codon 278 (CCT to C/ACT) in addition to a non-mutated codon, while only the wild-type p53 sequence was present in the paired primary gastric tumor tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗