Biomedical subjects
Publications and source records attributed to S K Chang.
A new azophenol type chromogenic ionophore based on the p-tert-butylcalix[4]arenediazacrown ether was prepared: the ionophore exhibited a pronouncedly selective chromogenic behaviour toward Hg2+ ions among the surveyed guests of alkali, alkaline earth, transition and heavy metal ions in liquid-liquid extraction experiments.
The Redox-active monolayer of a novel calix[4]arene recognizing redox-inactive ionic species by voltammetry is reported. Calix[4]arene-disulfide-diquinone, which is not only redox-active but is also a highly selective ionophore for the Ba2+ ion, spontaneously forms a stable and dense monolayer film on gold. The redox-active calixarene monolayer selectively recognizes Ba2+ ion in aqueous media, and the voltammetric signals are proportional to the ionic concentration. A new voltammetric peak can be detected by square-wave voltammetry upon adding a dilute solution containing Ba2+ ion having a concentration as low as 1.0 x 10(-6) M. The Langmuir plot (1/ip vs 1/[Ba2+]) shows a linear slope in the range from 1.0 x 10(-6) M to 1.0 x 10(-4) M. This modified electrode does not show any significant interference from alkali and alkaline earth metal ions except for Sr2+ and Ca2+. Only 100- and 500-fold concentrations of Sr2+ and Ca2+ ions, respectively, can lead to voltammetric responses comparable to that of Ba2+.
[reaction: see text] Chiral aziridine derivative 1 was prepared from D-tartaric acid. This compound could be utilized as a common intermediate for the synthesis of hydroxyethylamine class HIV protease inhibitors such as saquinavir, amprenavir, or nelfinavir.
BACKGROUND AND PURPOSE: To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. MATERIAL AND METHODS: Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20-70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1-6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. RESULTS: Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. CONCLUSIONS: Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.
The impact of clot stability affecting the vasculopathy and tissue necrosis in Shwartzman reaction was investigated using plasma Factor XIII A2-depleted rabbit (FXIII-DR). Plasma Factor XIIIA2 (FXIIIA2) was depleted by infusion of the mono-specific goat anti-rabbit FXIIIA2 IgG. Generalized Shwartzman reaction (GSR) was induced by priming and challenged by i.v. injection of LPS and local Shwartzman reaction (LSR) was primed by intradermal injection of LPS and challenged by i.v. injection of LPS. Histological examination of the GSR animals showed, extensive thrombi accumulation in renal tubules and bilateral cortical necrosis of kidney in 8 out of 10 rabbits but none in the FXIII-DR. Fibrinogen levels were elevated to 3 approximately 4 fold at 24 h and lowered at 48 h whereas a steady rise was seen in the FXIII-DR. FDP levels in GSR animals were significantly elevated at 24 h and further increased at 48 h but only slightly elevated in the FXIII-DR. Examination of the LSR tissues after 48 h showed an acute onset of progressive cutaneous vascular thrombosis, purpura, and secondary hemorrhagic necrosis whereas neither fibrin deposit nor necrosis of tissue were detected in FXIII-DR despite of an early edema formation. Fibrinogen levels were also increased two fold at 24 h but returned to basal levels at 48 h in control LSR animals but not affected at all in FXIII-DR. These results suggest that during the severe inflammatory conditions such as sepsis, the fibrinolytic system is functionally sufficient to dissipate the pathogenic accumulation of disseminated intravascular clots and exudated fibrin clots if those clots were prevented from getting crosslinked in plasma.
Areas of priority for intensive discovery would be the agbiotechnology and biomedical sectors using gene technology as a platform. The use of genetic manipulation in farming and the use of plants as 'pharma' factories to manufacture therapeutics would be on the rise. The human genome will continue to have a powerful impact on research and development of human diseases and healthcare. Discovery of genetics and pharmacogenomics will have great impact on drug development and will allow the prediction of the patient' s response to various drugs as well as the onset of individualised or 'designer drugs'. Human stem cells could have their cellular clocks reset by the cloning process, enhancing opportunities to grow young cells, tissues and organs for an aging population. The cellular clock could also be reset by therapeutic cloning. Bioinformatics would be a technology which would be synonymous with biotechnology. The analyses of biotechnology research would be conducted in silico and would involve the exchange of information among sophisticated computer databases. Applications of biotechnology would be even more evident in environmental technology, food development and food processing. In electronics, the use of the specificity of proteins in biochips is underway. In tandem with the explosions in research, regulatory issues, legislation and intellectual property rights will evolve to enhance the climate of discovery and innovation. Public education will have to be continually enhanced as awareness could negate any fear resulting from novel and innovative improvements from biotechnology.
This study concerns the spatial-frequency-tuned channels underlying infants' contrast sensitivity functions (CSFs) for red-green chromatic stimuli, and their relationship to the channels underlying infants' CSFs for luminance-modulated stimuli. Behavioral (forced-choice preferential-looking) techniques and stationary stimuli were used. In experiment 1. contrast thresholds were measured in 4- and 6-month-olds, using isoluminant red-green gratings with spatial frequencies ranging from 0.27 to 1.53 c deg. In experiment 2. contrast thresholds were measured in 4-month-olds. using both red-green and luminance-modulated gratings in the same low spatial frequency range. Covariance analyses of individual differences were performed. Experiment 1 revealed one dominant covariance channel for the detection of red-green gratings, with a second channel contributing to detection of the highest spatial frequencies used. Experiment 2 revealed two to three channels serving color and luminance: but surprisingly these channels were not statistically separable for luminance versus chromatic stimuli. Thus, covariance channels for color and luminance that are independent for adults [Peterzell & Teller (2000). Spatial frequency tuned covariance channels for red-green and luminance-modulated gratings: psychophysical data from human adults. Vision Research, 40, 417-430] are apparently interdependent in infants. These data suggest that for infants, detection thresholds for chromatic and luminance-modulated stimuli may be limited by common mechanisms.
The development of a dermatotoxicokinetic (dTK) model for p-nitrophenol (PNP), a common metabolite from a variety of compounds and a biomarker of organophosphate (OP) insecticide exposure, may facilitate the kinetic modeling and risk assessment strategy for its parent compounds. In order to quantify and then clarify in vivo-in vitro correlation of PNP disposition, multicompartment kinetic models were formulated. Female weanling pigs were dosed with [14C]PNP intravenously (150 microg in ethanol, n = 4) or topically onto non-occluded abdominal skin (300 microg/7.5cm2 in ethanol, n = 4). PNP and p-nitrophenyl-beta-D-glucuronide (PNP-G) profiles were determined in plasma and urine in addition to total 14C quantitation in many other samples. Disposition parameters (rate constants, Ftop, T12, T1/2Ka, AUC, Vss, Clp, MAT, and MRT) and the simulated chemical mass-time profiles on the dosed skin surface and in the local, systemic, and excretory compartments were also determined. Total recoveries of 97.17 +/- 4.18% and 99.80 +/- 2.41% were obtained from topical and intravenous experiments, respectively. Ninety-six hours after topical and intravenous application, 70.92 +/- 9.72% and 98.65 +/- 2.43% of the dose were excreted via urine, and 0.55 +/- 0.16% and 0.51 +/- 0.10% via the fecal route, respectively. Peak excretion rate and time were also determined. It was suggested by experimental observation and modeling that urinary 14C excretion correlates with the systemic tissue depletion profile well and may be used as a biomarker of PNP exposure. This study also supports the strategy of using urinary PNP as a biomonitoring tool for OP pesticide exposure, although some precautions have to be taken. The strategy used in this study will be useful in comprehensive dTK modeling in dermal risk assessment and transdermal drug delivery.
A matched-control study comparing standard radiotherapy versus neoadjuvant chemotherapy and radiation was undertaken to clarify the effects of neoadjuvant systemic chemotherapy for locally advanced squamous cell carcinoma of the maxillary antrum. Thirty-four patients with inoperable maxillary cancer were treated with neoadjuvant chemotherapy and radiotherapy (Group II). Before starting radiotherapy, all patients in Group II received two or three cycles of neoadjuvant chemotherapy consisting of cisplatin and a 5-day continuous infusion of 5-fluorouracil with or without intravenous injection of vinblastine. Radiation doses ranged from 66 Gy to 75 Gy (median, 70 Gy). The response rate, patterns of failure, toxicity, and survival for Group II were compared with those for 34 stage-matched patients treated with radiation alone (Group I). Despite a higher response rate to neoadjuvant chemotherapy, the recurrence rate and patterns of treatment failure were not influenced by the addition of neoadjuvant chemotherapy. In most cases, neoadjuvant chemotherapy did not interfere with subsequent radiotherapy, and radiation-induced late complications occurred equally in both treatment groups. After a median follow-up of 48 months, there was no significant difference in 5-year actuarial survival or disease-free survival between the two treatment groups. Radiation alone for inoperable maxillary cancer was clearly suboptimal for improving local control and survival rate, but neoadjuvant chemotherapy in addition to standard radiotherapy failed to demonstrate any therapeutic advantage over radiation alone.
A patient with a fulminant amebic colitis coexisting with intestinal tuberculosis had a sudden onset of crampy abdominal pain, mucoid diarrhea, anorexia, fever and vomiting with signs of positive peritoneal irritation. Fulminant amebic colitis occurring together with intestinal tuberculosis is an uncommon event and may present an interesting patho-etiological relationship. The diagnosis was proven by histopathologic examination of resected specimen. Subtotal colectomy including segmental resection of ileum, about 80 cm in length, followed by exteriorization of both ends, was performed in an emergency basis. Despite all measures, the patient died on the sixth postoperative day. The exact relationship of fulminant amebic colitis and intestinal tuberculosis is speculative but the possibility of a cause and effect relationship exists. Fulminant amebic colitis may readily be confused with other types of inflammatory bowel disease, such as idiopathic ulcerative colitis, Crohn's disease, perforated diverticulitis and appendicitis with perforation. This report draws attention to the resurgence of tuberculosis and amebiasis in Korea, and the need for the high degree of caution required to detect it.
The purpose of this study is to observe the influence of the methylenetetrahydrofolate reductase (MTHFR) gene (677C-->T substitution) on plasma homocysteine levels in end-stage renal disease (ESRD) patients who received a relatively large amount of folate (2 mg/d) and are undergoing hemodialysis. A cross-sectional study of plasma homocysteine, vitamin B(12), and folate was performed in patients with ESRD. The study population for the MTHFR gene study included 312 healthy subjects and 106 patients with ESRD undergoing hemodialysis. The C677T transition in the MTHFR gene was detected by HinF 1 restriction enzyme analysis and subsequent electrophoresis in a 3% agarose gel. The genotype of the MTHFR gene in 106 patients with ESRD was homozygous C677T mutation (VV) in 17 patients (16.1%) and heterozygous (AV) in 63 patients (58.4%); 26 patients (24.5%) did not carry this mutation (AA). The mean levels of homocysteine, vitamin B(12), and folate in the patients with ESRD were 23.3 +/- 14.0 mmol/L, 620.2 +/- 98.5 pmol/L, and 138.6 +/- 55.6 nmol/L, respectively. There was no significant difference in homocysteine levels among the three genotypes: 28.2 +/- 19.4 mmol/L for VV, 22.7 +/- 14.9 mmol/L for AV, and 23.4 +/- 11.1 mmol/L for AA genotype (P > 0.05). There was no difference in genotype distribution between the patient groups of less than 25th and greater than 75th percentiles, classified according to plasma homocysteine levels (P = 0.47). In conclusion, with high-dose folate supplementation, the hyperhomocysteinemia in patients with ESRD does not seem to be caused by the 677C-->T mutation in the MTHFR gene.
Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) is activated by a variety of cellular or environmental stresses. Proper regulation of the SAPK/JNK pathway may be critical for cell survival or death under various conditions. In this study, we report the molecular cloning of novel isoforms of JIP-1, which harbor a putative phosphotyrosine interaction domain and a helix-loop-helix domain, as well as an SH3 homologous region in the C terminus. Northern analysis indicates that transcription variant jip-1 is expressed in brain and kidney and transcription variants jip-2 and jip-3 are specifically expressed in brain. In situ hybridization data showed that the hybridized jip messages were heavily concentrated in adult brain, and were particularly enriched in the cerebral cortex and hippocampus, the brain regions vulnerable to pathological states such as hypoxia-ischemia, epilepsy, and Alzheimer's disease. All the deduced protein products of the jip transcription variants appear to have a similar property in that they inhibit the SAPK/JNK stimulation when overexpressed. Inhibition of SAPK activation by overexpression of the novel isoform JIP-2a resulted in suppression of etoposide-induced cell death in a neuroglioma cell line, N18TG. These findings suggest that JIP may play an important role in regulation of the SAPK pathway that is involved in stress-induced cellular responses.
Heat acclimation-induced sweating responses have the potential of reducing heat strain for chemical protective garment wearers. However, this potential benefit is strongly affected by the properties of the garment. If the clothing ensemble permits sufficient evaporative heat dissipation, then heat acclimation becomes helpful in reducing heat strain. On the other hand, if the garment creates an impenetrable barrier to moisture, no benefit can be gained from heat acclimation as the additional sweating cannot be evaporated. Ten subjects were studied exercising on a treadmill while wearing two different chemical protective ensembles. Skin heat flux, skin temperature, core temperature, metabolic heat production and heart rate were measured. It was found that the benefit of heat acclimation is strongly dependent on the ability of the body to dissipate an adequate amount of heat evaporatively. The evaporative potential (EP), a measure of thermal insulation modified by moisture permeability, of the clothing ensemble offers a quantitative index useful to determine, a priori, whether heat acclimation would be helpful when wearing protective clothing system. The data show that when EP is < 15%, heat acclimation affords no benefit. An evaporative potential graph is created to aid in this determination.
OBJECTIVE: Observe the relationship between homocysteine and other amino acids in patients with end-stage renal disease (ESRD). DESIGN: A cross-sectional study of amino acids and homocysteine and comparison of the correlations between ESRD and control group. SETTING: Nephrology unit of Soonchunhyang University hospital in Chunan, Korea. PARTICIPANTS: Forty-five ESRD patients and 30 control volunteers. MAIN OUTCOME MEASURES: Plasma amino acids and homocysteine. RESULTS: Concentrations of asparate, proline and cysteine were higher and serine, tyrosine, valine, isoleuline, leucine, and lysine levels were lower in the ESRD group than in control group. The branched chain amino acids (BCAAs) and essential amino acid were lower in the ESRD group than in the control group, but there was no difference in non-essential amino acid and total amino acid between the two groups. The mean plasma total homocysteine concentrations were 6 +/- 1 mmol/L in the control group and 14 +/- 4 mmol/L in the ESRD group (P < .001). In the ESRD group, homocysteine concentrations showed a direct correlation with the concentration of histidine (R2: .403, P < .001), valine (R2: .324, P < .01), leucine (R2: .400, P < .01), isoleucine (R2: .351, P < .005), cysteine (R2: .287, P < .001), methionine (R2: .256, P < .01), BCAA (R2: .50, P < .01), and essential amino acid (R2: .416, P < .01). In the control group, no correlation between the homocysteine and amino acid concentrations was found. CONCLUSIONS: Contrary to the control group, the homocysteine concentrations showed a direct correlation with the concentration of valine, leucine, isoleucine, methionine, and histidine levels in the ESRD group. Altered essential amino acid metabolism, specifically BCAAs and histidine, influence hyperhomocysteinemia in ESRD. Further study is needed to confirm this theory.
OBJECTIVE: Tuberous sclerosis is a genetic disorder with multisystem involvement. The aim of this study was to focus primarily on the cardiac aspects of this condition. METHOD: This review included 10 children with tuberous sclerosis presenting to our department during a 10-year period. RESULTS: From our data, 80% were found to have cardiac involvement. There was an equal prevalence of neurologic complications. CONCLUSIONS: Cardiac tumours and seizures were the most common problems encountered. Whereas most patients had no symptoms referable to the cardiovascular system and required no active intervention, many of those with neurologic involvement needed appropriate treatment.
In order to see whether conventional low-dose folic acid supplement along with vitamin B6 and B12 reduces hyperhomocysteinemia in patients with ESRD, we compared the levels of homocysteine, vitamin B6, B12 and folic acid among 3 groups of patients: 44 ESRD patients on hemodialysis with replacement of folic acid, vitamin B6, and B12 (dialysis group); 27 chronic renal failure patients without vitamin replacement (predialysis group); and 17 hypertensive patients without vitamin replacement (control group). Mean plasma total homocysteine concentration was higher in the dialysis (15.5 +/- 6.6 micromol/l) and the predialysis groups (15.7 +/- 4.2 micromol/l) than in the control group (6.2 +/- 1.5 micromol/l) (p < 0.001). However, there was no difference in homocysteine concentrations between the dialysis and predialysis groups. In the control and predialysis groups, the homocysteine concentration showed a reverse correlation with the concentrations of folic acid (r = 0.584, p = 0. 014 for the control group; r = 0.431, p = 0.247 for the predialysis group) and vitamin B12 (r = 0.485, p = 0.049 for the control group; r = -0.562, p = 0.023 for the predialysis group) but not with vitamin B6. In conclusion, plasma folic acid concentrations were 3-4 times higher in the dialysis than in the predialysis group. But these levels of folic acid are not enough to reduce hyperhomocysteinemia in ESRD.
OBJECTIVES: Long standing ulcerative colitis (UC) has been known to be one of the precancerous diseases of colorectal cancer. Although the frequent loss of p53 allele (LOH) and aneuploidy were reported as the molecular events in carcinoma and dysplasia known as the precursor of UC, p53 genetic alteration was not reported in indefinite dysplasia and UC involved mucosa in long standing UC. Therefore, we investigated the mutational inactivation of the p53 gene in UC patients who showed dysplastic mucosa, as well as non-dysplastic mucosa on H & E stain and, secondly, if there is p53 mutation, we examined the relationship between p53 alteration and clinical data. METHOD: Sixteen patients with UC who had different duration of colitis were studied by endoscopic examination with rectal mucosal biopsies, p53 gene alterations were detected by PCR-SSCP for exon 4-8 and immunohistochemical staining with p53 monoclonal antibody. RESULTS: Among 16 patients, 2 patients (12%) showed dysplasia on H-E stain. The p53 point mutations were detected in 4 (two dysplasia and 2 normal looking mucosa) on PCR-SSCP. 4 patients who had p53 gene mutation were positive in immunohistochemical staining. With regard to clinical characteristics, these patients with p53 point mutation showed poor response to medical treatment. CONCLUSION: These results suggest that the p53 mutation may be an early molecular event of cancerous change in UC.
An E. coli B Tab strain, EM121, was isolated that restricts T4 denA (DNA endonuclease II) mutants at 37 degrees C and above, but is permissive for wild-type T4 at all temperatures examined. At 42 degrees C, other mutants affected in nucleic acid metabolism (T4 dexA, regA and uvsW strains) are also restricted. Genetic analysis revealed that one mutation (rpoB5081) in the RNA polymerase beta subunit gene is sufficient for restricting all denA mutants. rpoB5081, together with a second linked mutation, is also required for restricting the other T4 mutants, rpoB5081 (P806S), previously shown to increase transcription termination in E. coli K-12, causes delayed synthesis of T4 late proteins and reduced DNA synthesis in denA infections. Thus, T4 DNA synthesis and gene expression are impaired by the rpoB5081 beta subunit when degradation of host DNA is reduced. Because the restricted T4 mutants are not readily distinguished from wild-type phage under typical plating conditions, EM121 is an important host for screening and mapping T4 denA mutations.