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Biomedical subjects

S S Hong

Publications and source records attributed to S S Hong.

At least 73 records · Page 4Linked to original sources

Flavivirus infection: essential ultrastructural changes and association of Kunjin virus NS3 protein with microtubules.

Virus-induced vesicles evolved early in the Kunjin virus replication cycle around 9 to 10 h p.i. just before the end of the latent period in infected Vero cells. About 2 h following the appearance of the vesicles, microtubule paracrystals were also formed. These two virus-induced structures seemed interlinked and have essential roles in Kunjin virus replication. A viral protein NS3 was found to be associated with the microtubule component of the cells. When vinblastine sulphate was added to the cells immediately after infection, formation of the paracrystals was delayed by two hours, and the affiliation of NS3 protein was also observed to be rearranged.

Animals↗

1-Hydroxyethylidene-1,1-bisphosphonate (HEBP) simultaneously induces two distinct types of hypomineralization in the rat incisor dentine.

Effects of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) on the dentinogenesis of the rat maxillary incisor were microradiographically examined 96 hours after a single subcutaneous injection. HEBP produced hypomineralized incremental bands in the enamel (HPOe) and in the dentine (outer HPO1 and inner HPO2) in a dose-dependent manner. In the labial dentine, both HPO1 and HPO2 did not extend apically beyond the apical limit of the HPOe and were thus located in the circumpulpal dentine. The two lesions in the labial dentine fully developed with a dosage of 10 mg/ P/kg or larger, and with 15 mg P/kg or larger, gross hypoplastic lesions developed. Therefore, histological analysis at shorter postinjection intervals was carried out on the labial dentine with 10 mg P/kg of HEBP. The HPO1 appeared along the dentine-predentine junction by 24 hours and was characterized by reduced numbers of inorganic crystals and 10 nm particles which invested the collagen fibrils. Therefore, the HPO1 was judged to be produced by the disturbance of transformation of the predentine to dentine. The precursor lesion of HPO2 appeared in the proximal predentine by 4 hours, and was characterized by reduced number of collagen fibrils and unusually coarse interfibrillar stippled material. This lesion migrated to the dentine by 96 hours and became the HPO2, which was characterized by reduced number of collagen fibrils. Individual collagen fibrils in the HPO2 were invested by as many inorganic crystals and 10 nm particles as in the normal dentine. The HPO2 is considered to be produced by the disturbance of organic matrix formation.

Animals↗

Increased tumor control rates in murine fibrosarcoma by combined therapy with L-alanosine and radiation.

L-Alanosine, an analog of L-aspartic acid, was investigated as one of a series of chemical compounds that may have inhibitory effects on the repair of potentially lethal damage caused by radiation using an in vivo murine fibrosarcoma (Meth-A tumor) in BALB/cBy male mice. The combined treatment of single administration of L-alanosine (600 mg/kg) and single dose of X-irradiation (20 Gy) on Meth-A tumors produced 62% tumor control, while the radiation alone resulted in less than 5% tumor control. The potentiating effect by L-alanosine was higher when the drug was administered 8 h prior to X-irradiation. The dose modification factor of the drug is estimated to be 1.4 for Meth-A tumor. The increased tumor control rates with combined alanosine and radiation were highly dependent upon the time and sequence of the combined treatment. The reason for reduced efficacy at treatment times of less than 8 h prior to X-irradiations appears to be related in part to the modulation of the body temperature by L-alanosine when combined with Ketamine, an anesthetic agent.

Alanine↗

Radiation toxicity of indium-111-2-mercaptopyridine-N-oxide on HeLa S-3 cells.

As one of a series of systematic studies to determine the cytotoxicity of radiopharmaceuticals, indium-111-2-mercaptopyridine-N-oxide (111In-merc) was studied using a monolayer of HeLa S-3 cells. Exponentially growing cells were incubated with up to 2.96 MBq/ml (80 microCi/ml) of 111In-merc (molecular ratio of In/Cd to merc was 1:1000) in phosphate buffered saline for up to 240 min at room temperature. Surviving fractions were assayed by the colony-forming method. The cell uptake curve was upward concave with increasing activity and was saturated after an incubation time of 60 min. A clonogenic assay resulted in an exponential dose-survival curve with a shoulder (D0 of 0.44 MBq/ml (12 microCi/ml); n = 5), and an upward concave time-survival relationship. Merc alone and decayed In-merc were non-toxic at the equivalent range, substantiating radiation-induced cytotoxicity of 111In-merc.

Cell Survival↗

Immunohistochemical localization of two types of carbonic anhydrase isozymes in oncocytoma and oncocytic epithelial cells.

An immunohistochemical study was performed on the localization of carbonic anhydrase isozymes I and II (CA I and CA II, respectively) in oncocytoma and oncocytic epithelial cells. Tumors examined were those deserved to be called oncocytomas such as Warthin's tumor, Hürthle cell tumor of the thyroid gland and renal oncocytoma. In addition, the same immunostaining was done on several pathologic lesions, accompanying moderate number of cells similar in tinctorial character to oncocytes, such as some type of adenoma of the thyroid gland, endometrial hyperplasia, endometriosis and so on. Specific antibodies against CA I and CA II prepared from human erythrocytes were converted into Fab' fragment and labeled with horseradish peroxidase. In each tissue sample, the majority of oncocytes or oncocytic epithelial cells showed a tendency to exhibit an immunostaining reaction for CA I and II intenser than that of adjacent original normal epithelium from which they might derive. To the authors' knowledge, no reports have been appeared on biological relevance of an increased activities of carbonic anhydrase in conjunction with a large number of mitochondria appearing in such oncocytic cells. In the present study, it is revealed that the immunoreactivities of CA isozymes increased in oncocytes as the number of mitochondria increased, suggesting that oncocytes have a high level of carbonic anhydrase for catalyzing the hydration of an increased amount of carbon dioxide generated chiefly via oxidative metabolism by mitochondria, the number of which is notably increased compensatorily for their deficient coupling of oxidative phosphorylation or other metabolic anomaly.

Adenoma↗

Ultrastructural histochemistry of carbonic anhydrase in rat osteoclasts.

Carbonic anhydrase (CA) was localized in osteoclasts of rat tibial metaphysis by light and electron microscopy using the histochemical method of Hansson. Ultrastructurally, positive staining was seen in the cytosol, mitochondrial cristae, Golgi apparatus, some nuclei and lysosomelike vesicles, and on the bone surface beneath the osteoclast. The presence of the enzyme within the Golgi ++apparatus, lysosomelike vesicles, and on the bone surface beneath the osteoclast suggests that some CA may be secreted into the resorbing zone. According to literature, the above localization of CA suggests that there may be three isozymes of CA in the rat osteoclast. These are ubiquitous cytosolic CA (CA-II), mitochondrial CA (CA-V) and secretory CA (CA-VI).

Animals↗

Analysis in the isolated perfused cat pancreas of factors implicated in the pathogenesis of pancreatitis.

This study describes the effect on the function and structure of the saline-perfused cat pancreas of factors implicated in the pathogenesis of pancreatitis (bile acid, ethanol, pancreatic enzymes) after their addition to the perfusion fluid or their instillation into the pancreatic duct. Instillation of trypsin or chenodeoxycholic acid, but not ethanol, into the pancreatic duct resulted in a profound suppression of secretory function. The leakage of perfusion fluid and amylase from the gland was also abruptly increased. Intraarterial perfusion of trypsin also inhibited secretin-induced flow and cholecystokinin evoked enzyme secretion. Intraarterial bile acid inhibited fluid flow but augmented enzyme secretion in a concentration-dependent manner. In addition, massive or focal parenchymal necrosis was caused by sustained intraarterial perfusion of bile acid or trypsin, respectively. Elastase and phospholipase A had little influence on pancreatic function or structure when added to the perfusion fluid. These findings show that pancreatic structure and function can be disturbed by potentially toxic factors administered not only via the ductal system but also via the vascular route, and consequently suggest that an "internal reflux" mechanism could be involved in the pathogenesis of pancreatitis in addition to a "ductal reflux" mechanism.

Amylases↗

Interaction of hyperthermia and pentamidine in HeLa S-3 cells.

Pentamidine is similar to rhodamine-123 in chemical structure and state of electron charge, and rhodamine-123 was previously shown to be a hyperthermic sensitizer under appropriate cell culture conditions. The present experiments were carried out to determine whether pentamidine would potentiate hyperthermic cell killing and, if so, under what cultural conditions. Exposure of HeLa cells to pentamidine (80 microM) up to 4 h was not cytotoxic in culture medium in the presence or absence of glucose at 37 degrees C and pH 7.4. Cells in the glucose-deprived medium became progressively sensitive to killing as temperature and drug concentration were increased. On the other hand, there was a moderate level of enhanced cell killing in the glucose-fed medium at 42 degrees C. The enhanced effects of heat by the drug were most pronounced under alkaline pH of the culture medium. The cell kill under acidic pH was far less than that observed at neutral or alkaline pH; these effects may be a result of decreased cellular uptake of pentamidine. Together with our previous results on rhodamine-123 and glycolytic inhibitors, the present data with pentamidine are consistent with the concept that deprivation of cellular energy increases sensitivity to cell killing by heat.

Amidines↗

Involvement of microtubules in Kunjin virus replication. Brief report.

Induction of microtubulin paracrystals (Pc) by Kunjin (KUN) virus occurred after 15 hours post-infection and were often associated with convoluted membranes (cm) and virus particles. Vinblastine sulphate which disrupts microtubulin, had an inhibitory effect on the virus production when added during the viral latent period. When infected samples were extracted with Triton X-100 and analysed by SDS-PAGE, four viral proteins were observed.

Animals↗

Functional relationship between initial oxidation of 7-ethoxycoumarin and subsequent conjugation of 7-hydroxycoumarin in isolated perfused rat livers.

Functional relationship between the initial mixed function oxidation of 7-ethoxycoumarin (EC) to 7-hydroxycoumarin (HC) and the subsequent conjugation of this metabolite to sulfate ester and glucuronide has been studied using isolated perfused rat livers. When increasing concentrations of EC (from 25 to 200 microM) were infused, perfused liver can oxidize only up to about 60 nmol of the infused EC to HC per min/g liver tissue. Most of this HC metabolite was released as sulfate ester, but there was a dose dependent shift to a more significant glucuronidation at the expense of the sulfate form. The dose dependent shift observed upon infusions with increasing dose of EC was not extensive so that the major portion of metabolite released was always the sulfate ester. However, the shift observed with HC was extensive and the major portion released was the glucuronide conjugate. Upon infusions with increasing concentrations of HC, the maximal rates of sulfation and glucuronidation were found to be 60 nmol and 120 nmol of HC conjugated per min/g liver tissue, respectively. Furthermore, the ranges in the rates of conjugation for the infused HC were divided into a sulfate ester 'zone' (less than 20 nmol), a dose-dependent shift 'zone' (between 20 and 180 nmol) with the 'cross-over' occurring at 80 nmol/min/g liver, and reaching the maximal conjugation 'capacity' rate (180 nmol), above which the unconjugated free form of HC was released. Under conditions when EC was infused into normal rat livers, the calculated maximal oxidation rate was only 60 nmol of HC produced/min/g liver. Consequently, under such a condition, the oxidation rate may never reach the 'cross-over' rate and this explains the lack of extensive dose-dependent shift and further indicates that there remained a large reserve conjugation capacity (120 nmol/min/g).

Animals↗

Induction of physical dependence by chronic alcohol treatment and enhancement of hepatic metabolism of 7-ethoxycoumarin and subsequent conjugation of its metabolite in perfused rat livers.

Physical dependence to alcohol was induced in rats and the rates of hepatic oxidation of 7-ethoxycoumarin to 7-hydroxycoumarin and of the subsequent conjugation of 7-hydroxycoumarin were studied using isolated perfused livers. Seven to 11.2 g of ethanol per kg body weight per day were given to rats in 2 divided doses at 10 a.m. and at 8 p.m. for 7, 9, 11, and 13 consecutive days. All rats surviving these courses of ethanol administration have demonstrated moderate degrees of withdrawal signs. In the isolated perfused livers obtained from these alcohol dependent rats, 100 microM 7-ethoxycoumarin was infused. The rate of 7-hydroxycoumarin formation was increased from 36 to 50 nmoles per min per g of liver tissue. This increase has occurred without significant changes of the liver weights. With such increase in the rate of mixed function oxidation, greater amounts of the 7-hydroxycoumarin metabolite were conjugated not only to glucuronide (from 4.9 to 6.7 nmoles), but also to sulfate ester (from 27.6 to 42.1 nmoles). Furthermore, a greater percentage of the produced metabolite was conjugated in the ethanol treated rat liver. A high concentration of 7-hydroxycoumarin (100 microM) was also infused in order to determine the effect of chronic alcohol administration on the maximal available rates of conjugation. Results indicated that the maximal rates of conjugation were significantly decreased. However, these decreased conjugation rates were still much greater than the maximal production rate for 7-hydroxycoumarin from the infused 7-ethoxycoumarin, for which the rate of oxidation has been elevated by the chronic ethanol treatment. Thus, the livers obtained from rats chronically treated with alcohol have increased rates for both the initial drug oxidation and the subsequent conjugation, even though the maximal rates of conjugation, per se, are reduced.

Animals↗

Involvement of histamine release in the mechanism of cysteamine-induced gastric acid hypersecretion.

To elucidate the mechanism of gastric hypersecretion induced by cysteamine, the effects of atropine, cimetidine, proglumide, cromolyn sodium and tranilast on the cysteamine response were studied in rats. Under urethane anesthesia, rat stomachs were perfused with 4 ml of physiological saline (pH 6.0) every 15 min. Acid secretion was progressively increased by cysteamine HCl (300 mg/kg, s.c.) for the duration of the experiment (6 hr). This effect was completely blocked by cimetidine and partially blocked by proglumide and atropine. Cromolyn sodium and tranilast, inhibitors of histamine release, also blocked cysteamine-induced acid hypersecretion. However, histamine-induced acid secretion was not affected by cromolyn sodium. It is concluded that the acid hypersecretion induced by cysteamine is mediated in part by histamine release.

Animals↗

[Radioprotective effect of local hypothermia].

We attempted local hypothermia to prevent radiation dermatitis and stomatitis. With regard to parasternal skin reactions postoperatively irradiated breast cancer, dry and moist desquamation, which occasionally occurred with conventional irradiation was not observed in combination with local cooling. As for head and neck tumors, patients who complained of stomatitis decreased with the local cooling, and no one wanted a pause in irradiation before 40 Gy. As local hypothermia is free from danger and does not require special equipment, it was considered to be widely applicable.

Aged↗

Combined treatment of radiation and local injections of misonidazole.

The radiosensitizing effect of misonidazole is dose dependent, so theoretically it would be desirable to use as large a dose as possible. However, clinical studies have indicated a maximum tolerable dose restricting the effects of misonidazole in patients. We injected misonidazole directly into tumor tissues in combination with irradiation in an attempt to obtain a sufficiently high concentration in tumors while maintaining a low level in the blood. Concentration of the drug in tumor tissues was confirmed to be high by examination of the resected low-grade chondrosarcoma into which the drug had been locally injected prior to the operation. Blood levels were confirmed to be significantly low. Seventeen patients were treated with local injections of the drug, each with radiotherapy. All patients either had advanced tumors, or were in the terminal stage after repeated radiotherapy and chemotherapy. A relatively high radiation dose per fraction was used. Complete response was obtained in eight patients (47%) and partial response in four (24%). No change was observed in three patients (18%) while two (12%) exhibited progressive disease. In the seven patients with multiple metastatic lesions, the response of the tumors treated with this method were compared to that of the tumors treated by radiation alone in the same patient. The sensitizing effect of the drug was clearly observed in three out of seven patients. No toxicities in the nervous system or in the gastrointestinal system were observed, and no local skin damage by the injections was seen. Local injections of misonidazole were shown to have a significant radiosensitizing effect without any side effects. The combined treatment of radiation and local injections of misonidazole is considered to be a promising new treatment method.

Combined Modality Therapy↗