The minimum graft size for successful orthotopic partial liver transplantation in the canine model.
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Biomedical subjects
Publications and source records attributed to S J Hong.
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Experimental ischemic stroke was induced by an occlusion of middle cerebral artery and common carotid artery of rats for 60 min. The occlusion was then released and the extent of neural damage was measured by the estimation of necrosis areas where the dead neurons lost their ability to take up triphenyl tetrazolium chloride. w-(N,N'-Diethylamino)-n-alkyl-3,4,5-trimethoxybenzoate (TMB) compounds are calcium antagonists capable of reducing intracellular free calcium through inhibition of calcium release from the sarcoplasmic reticulum. These compounds were found to prevent and/or reduce neural damage effectively. When the animals were pretreated with TMB-2, TMB-5 and TMB-8, 1 hr before ischemia, the areas of neural necrosis were reduced almost completely by 95%, 99% and 92%, respectively. When these TMB compounds were given at 0 time and 1 hr after ischemia, the prevention of necrosis was almost complete also. However, when TMB-2, TMB-5 and TMB-8 were administered 6 hr after ischemia, the necrosis areas were reduced less effectively by 83%, 78% and 91%, respectively. TMB compounds were also found to increase cAMP and to reduce intracellular free calcium concentration. These results indicate that TMB compounds are effective calcium antagonists to prevent/treat ischemic stroke by reducing the intracellular free calcium through reduction of calcium release from sarcoplasmic reticulum.
The effect of increased impulse activity upon voltage-dependent Ca2+ currents was studied in the cell body of a crayfish phasic motoneuron using two-electrode voltage-clamp technique. Increased electrical activity in this relatively inactive motoneuron produces a short-term and long-term reduction in the voltage-dependent Ca2+ current. Both forms of activity-dependent reduction in Ca2+ current are Ca2+ dependent. The short-term reduction in Ca2+ current appears to involve the Ca(2+)-dependent inactivation of Ca2+ channels, previously described in a variety of neurons. The long-term reduction in Ca2+ current is produced by prolonged Ca2+ influx and persists for days: in vivo stimulation of the phasic motor axon at 5 Hz for 1 hr results in a 30% reduction in Ca2+ current density, which persists for at least 3 d. Both the short-term and long-term reductions in Ca2+ current appear to result from changes in a single type of high-voltage-activated (HVA) Ca2+ channel. Inhibition of protein synthesis attenuates the long-term reduction in Ca2+ current and has no effect upon the short-term Ca2+ current reduction. During the long-term reduction in Ca2+ current, it appears that Ca2+ channels located distant to the site of Ca2+ influx are affected. The relationship of these results to a previously described Ca(2+)-dependent reduction in transmitter release is discussed.
When acetylcholinesterase was inhibited by neostigmine, SK&F 96365 (1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride) at 10 microM caused no effect on the amplitude of single endplate potentials (e.p.p.s) but shortened the decay time in mouse phrenic nerve-diaphragm preparations. However, SK&F 96365 inhibited high-frequency stimulation-evoked long-lasting depolarization of the endplate region and accelerated the run-down of trains of e.p.p.s which were eliminated within 1 s. After a train of stimulation, SK&F 96365 produced a post-tetanic depression of single e.p.p.s. The post-tetanic effect gradually dissipated with full restoration in 10-15 s. During a train of stimulation, SK&F 96365 also depressed miniature endplate potentials (m.e.p.p.s), which were restored after termination of stimuli in parallel with the recovery of e.p.p. The decay times of miniature endplate currents during recovery phases changed slightly. In control preparations not treated with neostigmine, however, SK&F 96365 did not alter the amplitude and decay time of m.e.p.p.s or e.p.p.s but accelerated the decay of succinylcholine-induced endplate depolarizations. The results suggest that SK&F 96365 facilitates nicotinic receptor desensitization in addition to blocking receptor-operated Ca2+ channels.
A cell-cell interaction model was developed to examine the intercellular communication between mesenchymal and epithelial cells in vivo, and to define the role of androgen and paracrine growth factors in promoting growth and differentiation of the target epithelial cells. Using this model system, we have demonstrated that, in the presence of androgenic steroids, a fetal urogenital sinus mesenchymal cell line exhibited androgen-induced growth responses which resulted in an induction of growth of a non-androgen target epithelial cell line derived from human urinary bladder. Our results show that: (1) a rat fetal urogenital sinus mesenchyme-derived cell line (rUGM) accelerated growth and conferred androgen-induced growth responsiveness upon a non-androgen target cell line, WH, derived from a human bladder transitional-cell carcinoma (TCC); this induction of epithelial tumor growth in vivo occurred in a fibroblast-specific manner; (2) live fetal rUGM cells are required to promote WH tumor growth in vivo, which suggests that continuous production of factors that may serve as mediators for paracrine/autocrine pathways are responsible for androgen stimulation of WH tumor growth in vivo; and (3) although WH tumor growth, mediated by the presence of rUGM cells, was markedly accelerated by the presence of androgen in vivo, androgen and rUGM cells failed to promote the expression of a human prostate-specific antigen (PSA) by WH tumors in vivo. Our results emphasize the importance of organ-specific fibroblasts that promote tumor growth and mediate androgen-induced growth responses; the accelerated growth of the bladder epithelium was not accompanied by the expression of PSA, a known differentiated gene product produced by human prostatic epithelial cells. This report also discusses the potential significance of mesenchymal-epithelial cellular interaction which mediates androgen action and may play an important role by influencing human prostate tumor growth, progression and differentiation.
An epidemiological study for the intestinal trematode infection of the villagers was done in Koje-myon, Kochang-gun, Kyongsangnam-do, Korea in March, 1994. Of 116 stool specimens examined, total helminthic ova positive cases were 13 (11.2%) and cumulative ova positive cases 21 (18.1%): Echinostoma hortense 11 cases (9.5%), Metagonimus sp. 6 cases (5.2%), and Clonorchis sinensis 4 cases (3.4%). After the treatment and purgation, variable numbers of E. hortense, 6 to 227 per person, were collected from 7 echinostome egg positive cases, together with M. takahashii in 6 cases. Three adult flukes of E. cinetorchis were collected from one person and one Stellantchasmus falcatus was recovered from another case. This mountainous village was proved to be one of the endemic foci of echinostomiasis in Korea.
Nine rabbits were fed with Clonorchis sinensis metacercariae (MC) and the blood samples chronologically obtained were analyzed biochemically. Rabbits infected by less than 100 flukes were grouped into Group I, and by 100-250 flukes into Group II. The serum level of alanine aminotransferase (ALT) was increased from 3 weeks after the infection of the metacercariae (AIM) and showed a peak at 8 weeks, and decreased from 12 weeks AIM. The serum level of aspartate aminotransferase (AST) was raised to 92.3 +/- 65.4 U/L at 3 weeks AIM and stayed high until 8 weeks, then lowered thereafter. The serum level of gamma-glutamyl transpeptidase (gamma-GT) was increased rapidly to the highest value (18.9 +/- 14.6 U/L) at 16 weeks AIM, and decreased to the control level after 20 weeks. The serum level of alkaline phosphatase (ALP) was headed down from the early infection to 52 weeks AIM. The serum cholesterol level was increased from 8 weeks and reached at a peak 16 weeks AIM, and decreased thereafter to the control level. It is suggested that serum ALT, AST, ALP and gamma-GT tests be useful to diagnose the early infection of C. sinensis.
Stools of the residents in a village in Saengbiryang-myon, Sanchong-gun, Kyongsangnam-do were examined for the eggs of intestinal helminths. In 1987, infection rate of 76 residents by Clonorchis sinensis was 80.3% with mean eggs per gram of feces (EPG) 27,781. C. sinensis-infected persons were treated once with praziquantel 60 mg/kg, q.i.d. Seventeen persons (22.4%) infected by Metagonimus yokogawai was coinfected with C. sinensis. In 1993, C. sinensis egg positive rate was 48.4% with mean EPG 5,929. Reinfection rate of follow-up cases by C. sinensis was 55.2% during 5 years and 5 months. Infection rate by M. yokogawai was 3.2%. This village was an endemic focus of clonorchiasis occurring reinfection high.
To investigate the possibility of in vivo transplantation of Leydig cells as a new biologic androgen replacement therapy, the Leydig cells procured from 6 week-old male Sprague-Dawley rats were autotransplanted, and the level of testosterone secretion and histostructural changes were observed. The renal subcapsular and intraperitoneal transplant showed higher levels of testosterone compared to subcutaneous or scrotal counterparts, and the number of transplanted cells was correlated with the level of measured testosterone. Furthermore, if the Leydig cells were transplanted intraperitoneally after the uptake on synthetic collagen, testosterone levels were higher than the ones simply transplanted without synthetic collagen uptake, resulting in 27 fold increase at 3 months. The activity of 125I-hCG decreased 20 to 40% at each month after transplantation compared to the normal levels, but no statistical significance was noted among different periods. The histologic examination revealed neovascularized capillaries and well demarcated sheet-like group of eosinophilic Leydig cells were observed at 4 weeks. But the evidence of destructive changes such as a focal inflammation with central dystropic ossification could be noted after 3 month. On electron microscopy, the marked indentation of nucleus and presence of lipochrome pigment were seen, and the number and size of smooth endoplasmic reticulum and mitochondria were reduced after 3 month. In conclusion, testosterone output could be increased to the physiologic range by increasing the number of transplant cells or utilizing collagen uptake but further effort is necessary on delaying or preventing the structural and functional decrement of Leydig cells.
One hundred and two patients with benign prostatic hyperplasia were treated by transurethral radio-frequency thermotherapy (TURT) device (Thermex-II, Direx, Israel) with 47.5 degrees C in single session for 2 hours and 30 minutes from November 1992 to October 1993. Among them, 83 patients, who were followed up for more than 3 months were included in this study. Twenty-seven (32.5%) patients had a history of acute retention. Pretreated values of the mean Madsen-Iversen symptom score, maximum urine flow rate, postvoiding residual urine volume, prostate volume and prostate specific antigen (PSA) were 15.4, 6.5 ml/sec, 61.3ml, 43.2ml and 0.77 ng/ml respectively. Madsen-Iversen symptom score, maximum urine flow rate were measured at 2 weeks, 1, 3 and 6 months after TURT. The residual urine volume, prostate volume and PSA level were measured at 3 and 6 months after TURT. During the follow up, the symptom score started to decrease significantly at 1 month (9.9, p < 0.01) after TURT, and gradually decreased up to 6.9 at 3 months. The maximum flow rate showed initial significant improvement at 2 weeks (8.1 ml/sec., p < 0.01), but no significant interval change was observed thereafter. The residual volume decreased significantly at 3 months (41.3 ml, p < 0.01) and no decrement was noted until 6 months. Neither the prostate volume nor PSA value changed significantly at 3 or 6 months after TURT. The improvement, which was defined as a change of 50% or more in at least one of subjective or objective symptoms showed in 63.9% (53/83) at 3 months and 57.1% (32/56) at 6 months. Both subjective and objective improvements at 3 and 6 months after treatment showed in 24.1% and 19.6%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
To document the correlation between renal damage and circadian blood pressure variation, urinary microalbumin excretion rate (UAER) and 24-hour ambulatory blood pressure monitoring (24-hr ABPM) were performed in 16 normotensives and 29 stage I-III essential hypertensive subjects (whole-day mean BP; 120.13/79.06 mmHg vs 152.59/94.31 mmHg, p < 0.05). The BP variables of 24-hr ABPM included hourly mean arterial pressure (MAP), maximum, minimum and mean systolic and diastolic BP of the awaking (daytime) and sleep time (nighttime), and whole-day mean BP. Subsequently, BP reduction of maximum, minimum and mean BP between awaking time and sleep time were also calculated as other variables. UAER was not different between the normotensive and hypertensive group (9.44 +/- 11.48 vs 11.87 +/- 9.27 micrograms/min, p > 0.05). 10 subjects (2/16 in normal vs 8/29 subjects in hypertensives) revealed over 16 micrograms/min of UAER. All of the awaking BP variables and whole-day mean BP were correlated with the UAER in whole subjects and hypertensives, but almost sleep BP variables except maximum DBP and mean DBP were not. On the contrary, only daytime minimum DBP and SBP were correlated with UAER in normotensives. The common best correlated BP variable in awaking time was minimum BP (DBP and SBP; r = 0.49, r = 0.44 in whole, r = 0.51, r = 0.58 in hypertensives, r = 0.54, 0.56 in normotensives, all p < 0.05). Hourly MAP at 24 PM in whole subjects (r = 0.49, p < 0.05) and that of at 22 PM in hypertensives were best correlated (r = 0.71, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVES: Infective endocarditis is still one of the important fatal diseases in Korea, especially when systemic embolisms are supervene. So, identification of patients who are in the high risk of embolism and who can be helped by early surgical intervention is very important. Considering these, we tried to elaborate the risk factors for the systemic embolism in patients with an infective endocarditis and the influence of systemic embolism on the mortality and morbidity in patients with an infective endocarditis. METHODS: We retrospectively reviewed the clinical records of 97 patients who were admitted with the infective endocarditis between January 1983 and October 1993. RESULTS: Among 97 patients, 80 patients met our diagnostic criteria. The mean age of patients was 38 years old. There were 43 males and 37 females. The mean duration of fever since the fever developed by history was 38 days. Valvular heart disease was the most frequent underlying heart disease. Mitral regurgitation and aortic regurgitation were the most common among valvular heart diseases. Pneumonia and acute pharyngotonsillitis were the most frequent predisposing factors of infective endocarditis. Blood cultures were positive in 51 patients (63.8%). Streptococcus viridans was the organism isolated most frequently, and Staphylococcus aureus was the second most frequently isolated one. Vegetations were detected in 58 patients (76.3%) by an echocardiography. Mitral valve and aortic valve were the most frequently involved incidence rate of embolism was 50% and the most frequent embolism site was the central nervous system and extremities were the next. Embolism occurred at the mean of 37 days after onset of fever. Overall in-hospital mortality rate was 26.3% and a cardiac-origin was the major cause of death. The only statistically significant risk factor for mortality was systemic embolism. The analysis of the relation between an incidence of embolism and the multivariables (age, presence of vegetation, location of vegetation, size of vegetation, causative organisms) showed that only the growth of Staphylococcus aureus had a significant trend toward a risk of subsequent systemic embolism. CONCLUSION: This study suggests that systemic emboli increases the mortality rate in patients with infective endocarditis. Age of patients, presence of vegetation, size and location of vegetation are not the risk factors for embolism, while certain organism, especially Staphylococcus aureus, could be a risk factor for the systemic embolism.
Stromal-epithelial interactions may play a key role in tumor growth and metastasis. We have established a model to study the cellular and molecular basis of this paracrine interaction both in vivo and in vitro using a human transitional cell carcinoma cell line (WH). s.c. coinoculation of 1 x 10(6) WH cells with 1 x 10(6) nontumorigenic fetal rat urogenital sinus mesenchymal (rUGM) cells in athymic mice accelerated carcinoma growth 20 times faster than isolated WH cell inoculations and 4 times faster than coinoculations of the same number of NIH-3T3 or human bladder fibroblasts. Characterization of these chimeric tumors with immunohistochemical and DNA dot-blot analyses documented their predominantly human component. To evaluate the underlying mechanisms involved in this paracrine-mediated in vivo tumor growth acceleration, Northern analyses for growth factors (GFs) and extracellular matrix (ECM) expression in the different cell lines, as well as in vitro mitogenic assays, were performed. Northern analysis revealed basic fibroblast growth factor, transforming growth factor alpha, and epidermal growth factor receptor expression by WH cells but not rUGM cells; ECM components (fibronectin and collagens I and IV) were expressed only in the fibroblast cell lines. Cell type-specific paracrine growth factors are produced by cultured stromal and epithelial cells with a 2-3-fold bidirectional increase in WH and rUGM cell growth when cultured with reciprocal cell-type conditioned medium. An autocrine growth loop was observed for WH but not rUGM cells. WH cell growth is stimulated in vitro by low concentrations of transforming growth factor alpha and epidermal growth factor, while rUGM cell growth is stimulated 3-fold by basic fibroblast growth factor. Antiepidermal growth factor receptor antibodies completely inhibited autocrine and paracrine pathways stimulating WH cell growth, while anti-basic fibroblast growth factor antibodies had no inhibitory effect. These observations suggest that autocrine and paracrine growth factor stimulation of WH bladder carcinoma cell growth is most likely mediated by an epidermal growth factor receptor-related pathway. The predominant expression of ECM by fibroblasts in this model suggests that stromal cell ECM components may modulate tumor cell growth and angiogenesis possibly through mechanisms involving cellular adhesion, chemotaxis, or growth factor action.
The acute changes of muscle tone and membrane current upon occlusion of oxygenation (O2 occlusion) were studied in vitro in mouse diaphragms. O2 occlusion immediately produced a contraction and a relaxation, respectively, in ryanodine- and high K(+)-contracted muscles while a biphasic change (an initial decrease then a late increase) of muscle tone was produced in muscles contracted with caffeine. The O2 occlusion effects were reversed after reoxygenation. CN- produced similar acute changes of muscle tone and abolished O2 occlusion effects. The O2 occlusion-induced relaxation in high K+ medium was converted into a contraction by 3,4-diaminopyridine and by low Cl- Tyrode's. O2 occlusion induced a small outward current and membrane hyperpolarization at a rate slower than the changes of muscle tone. Glybenclamide inhibited all of the changes induced by O2 occlusion. It is possible that the K+ and Cl- permeabilities of sarcoplasmic reticulum are highly sensitive to hypoxic challenge and related to the immediate changes of muscle tone after O2 occlusion.
Previous in vivo studies of crustacean neuromuscular synapses have shown that a chronic increase in the impulse activity of a previously 'inactive' motoneuron produces a reduction in initial transmitter release and greater resistance to synaptic fatigue. To explore the mechanisms of this synaptic change, we have developed an in vitro procedure for examining this activity-dependent reduction in initial transmitter release. We report that depolarization selectively applied to the proximal region of the neuron (cell body or axon) of a phasic motoneuron produces a reduction in initial transmitter release from the motor terminals. This synaptic change is observed 4-5 h after the beginning of depolarization. Proximal depolarization decreases initial transmitter release without reducing the capacity of the terminals to release transmitter during repetitive stimulation. Application of a calcium channel blocker during conditioning prevents the reduction in initial transmitter release. These results demonstrate that prolonged calcium influx produce a long-term reduction in initial transmitter release, and that calcium influx in distant regions of the motoneuron can influence transmitter release from motor terminals. The relationship of these findings to previously reported activity-dependent synaptic changes is discussed.
It has been reported that some dopamine antagonists can suppress the intraocular pressure and can increase the blood flow in the retina and choroid. Therefore, several dopamine antagonists and agonists were studied to determine if they can increase the ocular pulsatile blood flow in ocular hypertensive rabbits with the intraocular pressure raised artificially to 40 mm Hg. It was found that numerous dopamine antagonists including loxapine, moperone, domperidone, haloperidol and metoclopramide increased pulsatile blood flow for 49-110%, 95-155%, 72-86%, 60-114%, and 39-139%, respectively. Floropipamide reduced the ocular pulsatile blood flow for 18% at 90 min and 10% at 120 min. Chlofluperol produced biphasic action on pulsatile blood flow by significantly reducing it initially at 60 min (-49%) and then markedly increasing it at 180 min (91%). In case of dopamine agonists, neither dopamine nor bromocriptine affected the pulsatile blood flow significantly. These results indicate that some of dopamine antagonists could be used to lower the intraocular pressure and to increase the ocular pulsatile blood flow as well.
1. Local contraction of the endplate region in response to nerve stimulation was studied in isolated mouse diaphragms. In normal preparations, muscle contractions involved the whole length of the muscle fibre with rise and decay times in the order of tens of ms whether evoked with a single or train of pulses. 2. When acetylcholinesterase was inhibited with neostigmine, tetanic stimulation produced a twitch-like phasic contraction and a delayed tonic contracture. A brief train of pulse (10 ms, 300 Hz) was enough to trigger a full size tonic contracture which reached an amplitude about one tenth that of control tetanus and had a duration of about 4 s. 3. Tetanic stimulation evoked a non-propagating prolonged depolarization at the endplate region lasting for about 1 s following a few muscle action potentials. 4. mu-Conotoxin, a specific inhibitor of muscle Na+ channel, selectively abolished the phasic contraction and the muscle action potentials leaving the tonic contracture and the prolonged depolarization unaffected. 5. Both the tonic contracture and the prolonged depolarization were highly sensitive to blockade by tubocurarine (IC50 0.05-0.1 microM) and vesamicol (1 microM, an inhibitor of packaging acetylcholine into synaptic vesicles), were attenuated by increasing Ca2+ concentration and were prolonged by decreasing Ca2+. 6. The results suggest that prolonged activation of endplate nicotinic receptors by endogenously released transmitter can produce substantial contractions of the endplate region when acetylcholinesterase are inhibited. The source of Ca2+ for the contraction seems to come mainly from intracellular stores.
Worm recovery rates and pathologic changes in small intestine of albino rats were observed after concurrent and challenge infections with metacercariae (MC) of Fibricola seoulensis and Metagonimus yokogawai, and compared with those of single infection groups. Albino rats in concurrent infection group were killed 20 days after feeding with 1,000 MC of each fluke. Rats in challenge infection group were fed with 1,000 MC of F. seoulensis and challenged by 1,000 MC of M. yokogawai 10 days after primary infection, then killed 10 days thereafter. In concurrent infection group, mean number of F. seoulensis and M. yokogawai recovered, 250 and 118 respectively, were similar to those of single infection groups. However, more flukes were collected from the duodenum and less flukes were from the ileum than from single infection group. In challenge infection group, the recovery rate of F. seoulensis was similar to that of single infection group and the distribution of the flukes was similar to that of concurrent infection group. Mean number of M. yokogawai, 69, was significantly lower than that of single infection group. Its distribution, however, extended to the duodenum and most of the flukes were recovered from the jejunum. In concurrent infection group, villi of the duodenum were more markedly thickened, fused and shortened than those in F. seoulensis single infection group. The crypt epithelium appeared to be hyperplastic and inflammatory cell infiltration into the villous stroma was mild. Villous atrophy in the jejunum and ileum was milder than in M. yokogawai single infection group. In challenge infection group, the findings were similar to those of concurrent infection group.(ABSTRACT TRUNCATED AT 250 WORDS)