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Biomedical subjects

S Yi

Publications and source records attributed to S Yi.

At least 55 records · Page 3Linked to original sources

IL-10/Fc inhibits macrophage function and prolongs pancreatic islet xenograft survival.

BACKGROUND: Xenograft rejection is a complex response in which macrophages and other effector cells are activated by CD4+ T cells. Initiation and regulation of this response is in part mediated by cytokines. In this study we test the hypothesis that xenograft destruction is an interleukin- (IL) 10 responsive, macrophage-mediated event. METHODS: To study the effect of the systemic administration of IL-10 on pancreatic islet xenograft rejection, a fusion protein of IL-10/Fc was used. This immunoligand possesses the bioavailability of IL-10 and the long circulating t1/2 in vivo, characteristic of Ig. Wistar rat islets were transplanted into C57BL6 mice. IL-10/Fc was administered either immediately before transplantation or in the posttransplant period. RESULTS: Both therapeutic protocols prolonged xenograft survival. Macrophage effector function was reduced in IL-10/Fc-treated mice, with a reduced macrophage infiltrate, reduced IL-12 and tumor necrosis factor-alpha gene expression and reduced serum NO2- levels. Although the number of T cells infiltrating islet grafts was not reduced, T cell effector function was inhibited in IL-10/Fc-treated animals with reduced interferon-gamma and IL-4 gene expression, reduced anti-donor cytotoxicity by recipient splenocytes and reduced anti-donor IgG1 antibody production. Ultimate rejection of the xenografts appears to be mediated by a CD4+ T cell dependent mechanism probably as a result of inadequate inhibition of IL-12 production by macrophages. CONCLUSION: IL-10/Fc prolonged rat pancreatic islet xenograft survival by inhibiting macrophage mediated immune responses. The effectiveness of this agent when administered pretransplant suggests it may have a role as an induction agent with potential clinical application.

Animals↗

CD4+ cells play a major role in xenogeneic human anti-pig cytotoxicity through the Fas/Fas ligand lytic pathway.

BACKGROUND: In this study, the role of cell-mediated cytotoxicity by human leukocytes against pig endothelial cells was examined in vitro. The aim was to determine which cell subsets were responsible for this phenomenon and which pathways were involved in cell lysis. METHODS: Primed human peripheral blood mononuclear cells (PBMC) or purified CD4+ or CD8+ T cells were used in a cell-mediated cytotoxicity assay in which cytotoxicity of an SV40 transformed porcine endothelial cell (EC) line (SVAP) was determined by Annexin V binding. RESULTS: Human PBMC demonstrated specific lysis of porcine EC that was proportional to the effector: target ratio. CD4+ T cells accounted for >60% of this lysis, whereas CD8+ T cells accounted for <20%. CD4+ T cell-mediated lysis depended on direct recognition of porcine major histocompatibility complex class II molecules as inhibition of swine leukocyte antigen class II on porcine EC-inhibited CD4+ T cell cytotoxicity. This lysis was mediated through the Fas/FasL pathway as addition of anti-Fas and/or anti-FasL antibody profoundly inhibited antiporcine lysis. In addition, FasL gene expression was detected in primed PBMC and CD4+ T cells by RT-PCR, whereas granzyme B gene expression was not. Primed CD4+ T cells demonstrated high level FasL protein by Western blotting and two-color FACS analysis, whereas NK cells and CD8+ T cells did not. Finally, recombinant human FasL induced apoptosis in Fas expressing porcine EC cells, demonstrating that human FasL interacted with and activated Fas on porcine EC cells. CONCLUSIONS: In conclusion, human to pig cell-mediated cytotoxicity was mediated predominantly by CD4+ T cells through the Fas/FasL pathway of apoptosis. These results suggest that direct cytotoxicity by xenoreactive CD4+ T cells may be one of several effector mechanisms involved in cellular xenograft rejection.

Animals↗

Clinical study of orthokeratology in young myopic adolescents.

This project was designed to study the efficacy of orthokeratology and its related problems in a population of young myopic adolescents. Fifty-four young myopia adolescents ages 11 to 15 years were enrolled in the study and followed over a 6-month period. The procedures included (1) baseline refraction, assessment of tear quality and quantity, and cornea examination including cornea topography, A-scan ultrasound of cornea thickness, and spectromicroscopy of the corneal endothelium; (2) diagnostic lens fitting and evaluation; (3) lens dispensing and educating the patients or their parents; (4) follow-up schedule and data analysis; and (5) maintenance lens dispensing and analysis of wearing schedules. Myopia was reduced between -1.25 and -5.00 D (-3.00 D average). Myopia reduction was almost complete in the first 6 months, with most of the reduction occurring during the first 2 weeks. Seventy-five percent of the possible reduction occurred during this 2-week time period. Tear quality and quantity influenced reduction speed and amount. Corneal thickness and endothelium remained unchanged over the study period. Subjective refraction is the most reliable method to measure the status of ocular refractive changes. Corneal staining occurred in 45% of subjects during the procedure, mainly in subjects with tear problems. Eighteen percent of the subjects showed induced astigmatism, which could be reversed by refitting the lens or changing the wearing schedule. Maintenance lenses had to be worn every night for young adolescents to maintain myopia reduction. Orthokeratology is a reliable option for reducing some myopia in young adolescents. The first 2 weeks are critical for the procedure. Complete examination and the data analysis procedures are important for monitoring prognosis and eye health.

Journal Article↗

Lateralizing value of the Wada memory test in non-Western patients with temporal lobe epilepsy.

The Wada memory test measures a psychological construct (i.e. memory), which is widely acknowledged to be under the influence of a vast array of moderating variables including culture. Thus, the lateralizing value of the Wada memory test for epileptogenic foci may potentially differ for Western versus non-Western patients with temporal lobe epilepsy (TLE). In the present study, the lateralizing value of the Wada memory test was investigated in 17 Korean patients with medically intractable TLE who were post-operatively seizure-free. The Wada memory stimuli were composed of eight drawings of common objects, animals, and fruits. A clinical criterion of at least 2 points difference between left and right injections correctly classified 14 patients (82%) into left and right TLE groups, with only one patient (6%) falsely classified. This diagnostic accuracy is at least as high as that reported for Western TLE patients. These results indicate that whatever culture-specific factors Korean TLE patients may bring to the Wada memory test, they do not significantly reduce the lateralizing value of the test.

Adult↗

Paracrine effects of hepatocyte growth factor/scatter factor on non-small-cell lung carcinoma cell lines.

We have studied the mitogenic, motogenic and morphogenic effects of hepatocyte growth factor (HGF), also known as scatter factor (SF), on 15 non-small-cell lung carcinoma (NSCLC) cell lines that have had their ras genotype determined. HGF/SF stimulated proliferation in only three cell lines and exerted no mitogenic activity on six lines. The growth of the remaining six lines was inhibited. The mitogenic effects were not related to the ras genotype of these cell lines, but the inhibitory effect was more commonly observed in cell lines with relatively high levels of Met/HGF receptor (HGFR) expression. HGF/SF induced or enhanced both scatter activity on monolayer culture and single-cell invasion in collagen gels in approximately half of these cell lines. Although the ras genotype of tumour cells did not influence the HGF/SF-induced motogenic activity, cell lines with the mutant ras genotype more commonly demonstrated a spontaneous motogenic activity than those with the wild-type ras genotype. When tumour cells were grown in collagen gels, HGF/SF induced irregular branching extensions of cell aggregates formed by five out of eight adenocarcinoma cell lines, but significant lumen morphogenesis was distinctly absent. The presence of autocrine HGF/SF loop in these tumour cell lines did not influence their spontaneous or HGF/SF-induced mitogenic, motogenic or morphogenic activities. Overall, our data suggest that stimulation of cell motility, rather than proliferation or differentiation, is the predominant paracrine effect of HGF/SF on NSCLC cells in vitro.

Carcinoma, Non-Small-Cell Lung↗

Calcipotriene-induced improvement in psoriasis is associated with reduced interleukin-8 and increased interleukin-10 levels within lesions.

Calcipotriene is a synthetic analogue of 1,25-dihydroxyvitamin D3 established to be effective topically in the treatment of psoriasis. We investigated the early cellular and immunological events induced by calcipotriene in psoriasis. Thirty patients with moderate plaque-type psoriasis were randomly assigned to receive twice daily applications of either calcipotriene ointment 0.005% or matching vehicle for 6 weeks. Skin biopsies (6 mm) were performed from designated plaques at baseline and days 3 and 7. On these days and at weeks 2, 4 and 6, complete clinical evaluations were made in a double-blind fashion. Consistent with previous studies, significant clinical improvement (P < 0.05) in psoriasis was observed in patients receiving calcipotriene vs. those receiving vehicle by day 7 for scale and erythema, and by day 14 for thickness. No significant improvement, however, was seen on day 3. None of the immunohistological markers (CD1a, CD4, CD8, ICAM-1, VCAM-1, E-selectin, HLA-DR) semiquantitatively assessed in psoriatic plaques was significantly changed by calcipotriene treatment for 7 days. In the calcipotriene-treated group, interleukin (IL)-10 levels (pg/microgram of protein) increased by 57% from baseline (0.030 +/- 0.006; mean +/- SEM) to day 3 (0.047 +/- 0.011) (P = 0.05 vs. baseline; n = 10) and remained elevated at day 7 (0.046 +/- 0.012). IL-8 levels (pg/microgram of protein), however, declined by 70% from baseline (0.13 +/- 0.06) to day 3 (0.04 +/- 0.01), and remained low at day 7 (0.03 +/- 0.02) (P < 0.05 vs. baseline; n = 10). Both IL-8 and IL-10 were unaffected by vehicle treatment. Calcipotriene-induced clinical improvement of psoriasis is preceded by an increase in IL-10 and a concomitant decrease in IL-8 levels. The changes in the level of these two cytokines provide further evidence for immunological changes as a significant part of the mechanism of action of calcipotriene in psoriasis.

Adolescent↗

Financing changes of schistosomiasis control programmes in China 1980-1995: a case study in Songzi county.

To assess the financing changes of schistosomiasis control programmes in China and estimate the impact of these changes on patients' treatment-seeking behaviour and control of schistosomiasis, a survey was conducted in five schistosomiasis-endemic areas of the lake regions, Hubei province, in 1996. This paper reports financing changes and their impact on the incidence and prevalence of schistosomiasis from one of the five areas as a case study. By examining the surveillance and financial data from 1980 to 1995, and through focus group discussions we found that the schistosomiasis control programmes in People's Republic of China have gone through dramatic financing changes from 1980 to 1995, when the transitions of China's social, economic, and political systems happened. The proportions of funding to schistosomiasis control programmes from high level governmental agencies, county budgets, and services revenue changed from 60%, 23%, and 17%, respectively, in 1980-1987 to 0.7%, 22.3%, and 72% in 1995. The percentages of expenditure of schistosomiasis control activities, salaries and bonuses, and other activities unrelated to schistosomiasis control, were 53.5%, 14.4, and 17.2% in 1980. These percentages changed to 7.7%, 33.3%, and 53.3%, respectively, in 1995. The preponderant role of the state in organizing, financing, and delivery of the services was replaced with the new system which is more influenced by the market economy. The incidence and the prevalence of schistosomiasis in the study area have increased year by year from 1980 to 1990, although there has been a tendency to decrease after 1991 but not to the low pre1980 levels. The collapse of the community-based medical system in rural areas and the dramatic financing changes of schistosomiasis control programmes have created major difficulties for schistosomiasis control in China.

China↗

Transsphenoidal microsurgical removal of large pituitary adenomas.

OBJECTIVE: To retrospectively analyze the diagnostic modes, transsphenoidal microsurgical technique and outcomes of 145 patients with pituitary macroadenoma or giant pituitary adenoma. METHODS: A total of 145 patients suffering from pituitary macroadenoma or giant pituitary adenoma with suprasellar extension were performed with transsphenoidal microsurgery in our department. Diagnoses were made by CT or MRI scanning. All adenomas had suprasellar extension (extension size: > 10 mm). Operations were performed via either sublabio-septo-sphenoidal approach or naso-vestibulo-sphenoidal approach under microscope. During operation, a subarachnoid catheter was inserted into the lumbar cistern, via the catheter saline was slowly injected to increase the intracranial pressure (ICP) and to deliver the suprasellar tumor into the operative field for easy removal. RESULTS: The gross total removal of adenoma in 102 patients (70.4%) and subtotal removal in 35 patients (24.1%) were achieved; partial removal was carried out in the remaining 8 patients (5.5%) with fibrous or dumbbell-shaped adenomas. There were no deaths after surgery. Long-term follow-up observation (median: 3.5 years) in 132 patients revealed good recovery in 93 (70.5%) and late recurrence in 39 (29.5%). Those patients with tumor recurrence underwent reoperation, drug therapy, radiotherapy, and radiosurgery either alone or in combination. CONCLUSION: Except for fibrous and dumbbell-shaped ones, microsurgical technique via transsphenoidal approach is a safe and effective way to remove large pituitary adenomas.

Adenoma↗

Development neurobiology of the stress response: multilevel regulation of corticotropin-releasing hormone function.

The ability to respond to adverse environmental cues is present in the neonatal and infant rat, although in an immature form: A number of laboratories have demonstrated stress-induced elevations of plasma glucocorticoids during the first two postnatal weeks. The limbic and hypothalamic mechanisms controlling the hormonal stress-response during this period are not fully understood and are, therefore, the focus of this report. Both hypothalamic corticotropin-releasing hormone (CRH) and vasopressin contribute to the release of ACTH from the pituitary in the adult. The relative roles of these two peptides during the neonatal (first week) and infant (second week) developmental period, are controversial. Evidence is presented that argues strongly for a major role for CRH. Up-regulation of hypothalamic CRH synthesis is a major component in the mature stress response. CRH-mRNA levels in the hypothalamic PVN are increased with cold stress by ninth postnatal day, but not during the first postnatal week. Further, down-regulation of CRH gene expression by glucocorticoids (GC) constitutes a critical "shut-down" mechanism for the hormonal stress response. In vivo and in vitro experiments supporting the "immaturity" of GC feedback on CRH synthesis during the first postnatal week are described. CRH-mediated neurotransmission, in both the endocrine and neuronal effector arms of the response to stress may be modulated via alteration of receptor number. The first member of the CRH receptor family, CRF1, probably mediates the neuroendocrine effects of CRH. The developmental profile of CRF1-mRNA reveals several distinctive spatial and temporal patterns. In the hippocampal CA1, CA2, and CA3a peak (300-600% adult values) CRF1-mRNA is found on postnatal day 6. In the amygdala, CRH receptor mRNA levels are maximal on the ninth postnatal day (at 180% of adult values). In cortex, a steady decline from high postnatal day 2 levels results in adult levels by 12. These findings demonstrate distinct, regional, age-specific control of the synthesis of CRF1. Receptor expression profile may provide important information regarding modulation of the age-specific roles of CRH in different regions. For example, a high ratio of hippocampus/amygdala receptors may preferentially activate negative hippocampal input to the hypothalamus during the neonatal period. Additionally, increased CRH receptor mRNA in the infant compared with the adult provides a mechanism for enhanced excitatory effect of the peptide at this age. In conclusion, increasing evidence exists for multiple control points of the early postnatal response and adaptation to stress. CRH synthesis in hypothalamus and amygdala, its sensitivity to GC feedback, and the abundance and distribution of at least two distinct CRH receptors in the limbic central nervous system and the pituitary are developmentally regulated. All serve as control points permitting an effective endocrine, autonomic, and behavioral response to stressful environmental cues.

Age Factors↗

Comparison of amyloid deposition in two lines of transgenic mouse that model familial amyloidotic polyneuropathy, type I.

We previously produced a transgenic mouse line designated MT-hMet30 by introducing the human mutant transthyretin (TTR) gene carrying the mouse metallothionein promoter, and showed that the presence of human variant TTR is sufficient for amyloid deposition in various tissues of these transgenic mice. However, the expression pattern of human mutant transthyretin gene in the mouse was different from that in man. To analyse pathologic processes, it is essential to establish a transgenic mouse line in which the development and tissue-specific expression of the human mutant TTR gene is the same as in man. Thus, we produced two additional transgenic mouse lines carrying the human mutant TTR gene containing either 0.6 kb (0.6-hMet30) or 6.0 kb (6.0- hMet30) of the upstream region. The expression levels of 6.0-hMet 30 gene in the liver and serum were the same as in man and about 10 times higher than those of 0.6-hMet30 gene in the liver and serum were the same as similar tissues to human patients except for the peripheral and autonomic nervous tissues. The amyloid deposition started earlier and was more extensive in 6.0-hMet30 than 0.6-hMet30 mice, suggesting that the serum levels of human mutant TTR are correlated with the occurrence and degree of amyloid deposition, to some extent. Neither amyloid deposition nor degenerative changes were observed in the peripheral and autonomic nervous systems despite the transgene expression in the choroid plexus of the 6.0-hMet30 mice. In the 6.0-hMet30 mice, amyloid deposition started at 9 months of age, although the serum level of human mutant TTR reached the adult level at 1 month. These results suggest that intrinsic environmental factors other than the mutant gene are involved in the late-onset deposition of amyloid fibrils. Transgenic mice described here should be useful for analysing such factors.

Age Factors↗

The effect of early versus late onset of temporal lobe epilepsy on hemispheric memory laterality: an intracarotid amobarbital procedure study.

Thirty-three temporal lobe epilepsy (TLE) patients, 19 left TLE and 14 right TLE, underwent an intracarotid amobarbital procedure. For each patient, hemispheric memory laterality was determined by measuring the relative magnitude of recognition memory following left versus right hemisphere injection of sodium amobarbital. The patients were divided into early and late seizure onset groups, based on the median age (13 yrs) of seizure onset of the total sample. Early-onset left TLE was associated with a greater tendency toward right hemispheric representation of both verbal and visual memory compared with late-onset left TLE. Early-onset right TLE was associated with a greater tendency toward left hemispheric representation of visual, but not verbal, memory compared with late-onset right TLE. These findings indicate that interhemispheric plasticity for memory is greater in early than in late life, bidirectional, and at least partially material-specific.

Adolescent↗

[Relation of continuous ICP, CPP monitoring with prognosis for severe brain injury].

We analysed the treatment results of two groups of patients. Group I included 50 patients with severe brain injury with GCS 3-8, on whom continuous intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring was performed and Group II included 50 cases of similar patients, on whom no continuous ICP monitoring was performed. In Group I 8 patients had normal ICP (< 2.0 kPa), CPP (> 9.33 kpa), and the rest 42 had increased, ICP and reduced CPP. After adequate intervention including operation and drug treatment, group I patients had good results with a mortality of 14%. Group II patients received the same intervention based on clinical observations, but they had relatively worse results. We are of the opinion that continuous ICP and CPP monitoring for severe brain injury patients helps find proper treatments and reduce mortality.

Adolescent↗

Zipeprol (Zinolta) abuse among American adolescents in Korea: a discussion of the problem, clinical presentation, and treatment.

Zipeprol dihydrochloride (Zinolta) is a Korean medication that is abused by American dependent teenagers in Korea. The adolescents usually present for medical care after a seizure. Since this medication is not available in the United States, many physicians are unfamiliar with zipeprol-induced seizures. The extent of the problem, the pharmacology and mechanism of action of zipeprol, the clinical presentation, and suggestions for treatment are discussed. Military physicians should consider zipeprol overdose when a teenager presents with a seizure.

Adolescent↗

[Restricting effects of geologic background system on genuine crude drugs in Sichuan].

The distribution, growth, output and quality of genuine crude drugs are restricted by geologic background system (GBS), whose extensional vector system "rock-->soil-->medicinal plants" accomplishes the unity of geological grand cycle and biological pulmonary circulation. This article describes how genuine crude drugs in Sichuan, such as Coptis chinensis, etc. for example, are restricted by GBS.

Animals↗

[Establishment of human amnion cell mutagenesis system by using a shuttle vector pS189].

Using transient shuttle vector pS189, we established a subclone human amnion cell (FL) mutagenesis detection system, and we detected the mutation specificity of N-methy-N'-nitro-N-nitrosoguanidine (MNNG) in this system. The spontaneous mutant frequency of target gene supF was 1.7 x 10(-5) and MNNG-induced mutant frequency was increased with dosage. The results from 0.8% agarose gel electrophoresis, PCR, PCR-single strand conformation polymorphism (PCR-SSCP) analysis showed that MNNG-induced 89% mutants were point mutants. These results indicated that this system can be used to detect and study the mutagenesis mechanism of potential mutagens.

Amnion↗

A 6-kb upstream region of the human transthyretin gene can direct developmental, tissue-specific, and quantitatively normal expression in transgenic mouse.

To ascertain whether a 6-kb upstream region of the human transthyretin (TTR) gene contains the cis-element(s) required for proper specificity and level of expression, transgenic mice carrying the human mutant TTR gene containing either 6-kb (6.0-hMet30) or 0.6-kb (0.6-hMet30) of the upstream region were produced and studied. The 6.0-hMet30 gene was expressed in the yolk sac, liver, and choroid plexus, where the mouse endogenous TTR gene is also expressed. In contrast, expression of the 0.6-hMet30 gene was restricted to the yolk sac and liver. The expression levels of the 6.0-hMet30 gene in the liver and serum were similar to those of the mouse TTR gene, and about 10-fold those of the 0.6-hMet30 gene. Before birth, the developmental profiles of the expression of both transgenes in each tissue were similar to those of the mouse TTR gene. However, the expression levels of the 6.0-hMet30 gene in the liver and serum increased after birth to reach adult levels at an age of 4 weeks, while expression of the 0.6-hMet30 gene remained at a low level after birth. These results suggest that the 6-kb upstream sequence contains the cis-elements required for developmental, tissue-specific, and quantitatively normal expression.

Animals↗