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Biomedical subjects

S Hwang

Publications and source records attributed to S Hwang.

At least 91 records · Page 5Linked to original sources

Overexpression of ATP sulfurylase in indian mustard leads to increased selenate uptake, reduction, and tolerance

In earlier studies, the assimilation of selenate by plants appeared to be limited by its reduction, a step that is thought to be mediated by ATP sulfurylase. Here, the Arabidopsis APS1 gene, encoding a plastidic ATP sulfurylase, was constitutively overexpressed in Indian mustard (Brassica juncea). Compared with that in untransformed plants, the ATP sulfurylase activity was 2- to 2.5-fold higher in shoots and roots of transgenic seedlings, and 1. 5- to 2-fold higher in shoots but not roots of selenate-supplied mature ATP-sulfurylase-overexpressing (APS) plants. The APS plants showed increased selenate reduction: x-ray absorption spectroscopy showed that root and shoot tissues of mature APS plants contained mostly organic Se (possibly selenomethionine), whereas wild-type plants accumulated selenate. The APS plants were not able to reduce selenate when shoots were removed immediately before selenate was supplied. In addition, Se accumulation in APS plants was 2- to 3-fold higher in shoots and 1.5-fold higher in roots compared with wild-type plants, and Se tolerance was higher in both seedlings and mature APS plants. These studies show that ATP sulfurylase not only mediates selenate reduction in plants, but is also rate limiting for selenate uptake and assimilation.

Journal Article↗

Complex behavior of self-propagating reaction waves in heterogeneous media.

Self-propagating high temperature reaction waves, leading to the synthesis of advanced materials, are investigated in a variety of heterogeneous reaction systems by using a digital high-speed microscopic video recording technique. It is shown that, although on the macroscopic length and time scales, the reaction appears to move in a steady mode, on the microscopic level it has a complex character that is related to the reaction mechanism.

Aluminum↗

Multiple-dose pharmacokinetics and pharmacodynamics of OROS and immediate-release amitriptyline hydrochloride formulations.

The pharmacokinetics and pharmacodynamics of amitriptyline hydrochloride after oral administration of an OROS osmotic system, which provides controlled drug delivery, and an immediate-release (IR) tablet, were evaluated in 24 healthy volunteers after repeated administration for 14 days. Each morning, subjects received either 75 mg of the OROS (amitriptyline HCl) controlled-release formulation or the 75 mg IR amitriptyline tablet for 14 days on two separate occasions with a washout period of 21 days according to a randomly assigned sequence. Serial blood samples were collected for a period of 58 hours after the day 14 dose, then these samples were analyzed by the gas chromatography method for amitriptyline and nortriptyline. Subjective ratings of dry mouth and drowsiness were collected at specific times throughout each treatment period. Administration of the OROS formulation resulted in much more consistent plasma concentrations of the drug and metabolite compared with the IR formulation at steady state. The mean maximum concentration (Cmax) of amitriptyline was significantly lower after administration of OROS than the IR formulation. Mean values for area under the concentration--time curve (AUC0-24) for the OROS and IR formulations were 1,265 and 1,393 ng. hr/mL, respectively. The drug-to-metabolite ratio was found to be similar for both treatments, suggesting that there was no difference in metabolism between treatments. Incidence and severity of the anticholinergic effects were similar for the two treatments. A clockwise hysteresis between baseline-corrected drowsiness and drug concentration suggests development of tolerance of the anticholinergic effects after both treatments. Using a hypothetical anatagonist metabolite model to explain tolerance development, the shape of the hysteresis curves of the two treatments could be explained by differences in dosing frequency.

Adult↗

Complications after microsurgical tissue transfer in the head and neck region.

In recent years, the use of microsurgically re-anastomosed free transplants has become a proven technique for the reconstruction of defects in the head and neck region, which is demanding from both aesthetic and functional points of view. A retrospective catamnestic study on 227 free tissue transfers in the Department for Oral and Maxillofacial Surgery at the University of Tübingen showed good healing with relatively low failure rates of the transplants used. A significant proportion of local complications, arising postoperatively, was to some degree due to pre-existing medical conditions, tumour-specific pretreatments and the particular wound-healing situation found in head and neck interventions. The highest relative rate of complications at the site of origin was seen amongst osteomuscular transplants (20%) whilst (fascio) cutaneous and visceral transplants were found to result in a low percentage of problems (4%). In contrast, the healing of iliac crest transplants was accompanied by various local complications in 12% of the cases, slightly higher than 20% amongst (fascio) cutaneous and abdominal transplants and well above 30% for latissimusdorsi and scapular transplants. General complications, in particular of a respiratory and/or psychiatric nature, were found in 23% of the patients.

Adult↗

The mouse H19 locus mediates a transition between imprinted and non-imprinted DNA replication patterns.

Genes subject to genomic imprinting generally occur in clusters of hundreds of kilobases. These domains exhibit several gamete of origin-dependent manifestations, including a pattern of asynchronous replication when studied by fluorescence in situ hybridization (FISH). We find a transition from asynchronous replication at the imprinted mouse H19 gene to synchronous replication at the downstream Rpl23 gene, the human homologue of which appears to be non-imprinted. Two-colour FISH demonstrates that this transition is due solely to a difference in replication timing between the upstream and downstream chromatin on the later-replicating (maternal) chromosome. This difference is lost in mice deleted for the H19 gene body and 9.9 kb of upstream DNA when this deletion is maternally inherited, with synchronous replication patterns extending over 110 kb upstream from the deleted area. No effect is seen when the deletion is paternally inherited. The presence of a boundary element in this region has been suggested by observations of position-independent expression of H19 -containing transgenes and the blocking of accessibility of downstream enhancers to the upstream Igf2 and Ins2 genes on the maternal chromosome. The FISH studies presented here demonstrate the insulation of replication patterns within the imprinted domain from downstream, non-imprinted chromatin, mediated by an element at the H19 locus which is subject to genomic imprinting.

Animals↗

Rate-limiting steps in selenium assimilation and volatilization by indian mustard

Se can be accumulated by plants and volatilized to dimethylselenide, providing an attractive technology for Se phytoremediation. To determine the rate-limiting steps in Se volatilization from selenate and selenite, time- and concentration-dependent kinetics of Se accumulation and volatilization were studied in Indian mustard (Brassica juncea). Time-dependent kinetic studies showed that selenate was taken up 2-fold faster than selenite. Selenate was rapidly translocated to the shoot, away from the root, the site of volatilization, whereas only approximately 10% of the selenite was translocated. For both selenate- and selenite-supplied plants, Se accumulation and volatilization increased linearly with external Se concentration up to 20 &mgr;M; volatilization rates were also linearly correlated with root Se concentrations. Se-volatilization rates were 2- to 3-fold higher from plants supplied with selenite compared with selenate. Se speciation by x-ray absorption spectroscopy revealed that selenite-supplied plants accumulated organic Se, most likely selenomethionine, whereas selenate-supplied plants accumulated selenate. Our data suggest that Se volatilization from selenate is limited by the rate of selenate reduction, as well as by the availability of Se in roots, as influenced by uptake and translocation. Se volatilization from selenite may be limited by selenite uptake and by the conversion of selenomethionine to dimethylselenide.

Journal Article↗

Enteric beta-defensin: molecular cloning and characterization of a gene with inducible intestinal epithelial cell expression associated with Cryptosporidium parvum infection.

A growing body of evidence suggests that endogenous antibiotics contribute to the innate defense of mammalian mucosal surfaces. In the cow, beta-defensins constitute a large family of antibiotic peptides whose members have been previously isolated from the respiratory and oral mucosa, as well as circulating phagocytic cells. A novel bovine genomic clone with beta-defensin-related sequence [corrected] related to those of these alpha-defensins was isolated and characterized. The corresponding cDNA was isolated from a small intestinal library; its open reading frame predicts a deduced sequence of a novel beta-defensin, which we designate enteric beta-defensin (EBD). Northern blot analysis of a variety of bovine tissues revealed that EBD mRNA is highly expressed in the distal small intestine and colon, anatomic locations distinct from those for previously characterized beta-defensins. EBD mRNA was further localized by in situ hybridization to epithelial cells of the colon and small intestinal crypts. Infection of two calves with the intestinal parasite Cryptosporidium parvum induced 5- and 10-fold increases above control levels of EBD mRNA in intestinal tissues. An anchored-PCR strategy was used to identify other beta-defensin mRNAs expressed in the intestine. In addition to that of EBD, several low-abundance cDNAs which corresponded to other beta-defensin mRNAs were cloned. Most of these clones encoded previously characterized beta-defensins or closely related isoforms, but two encoded a previously uncharacterized prepro-beta-defensin. Northern blot evidence supported that all of these other beta-defensin genes are expressed at levels lower than that of the EBD gene in enteric tissue. Furthermore, some of these beta-defensin mRNAs were abundant in bone marrow, suggesting that in enteric tissue their expression may be in cells of hematopoietic origin. Extracts of small intestinal mucosa obtained from healthy cows have numerous active chromatographic fractions as determined by an antibacterial assay, and one peptide was partially purified. The peptide corresponded to one of the low-abundance cDNAs. This study provides evidence of beta-defensin expression in enteric tissue and that the mRNA encoding a major beta-defensin of enteric tissue, EBD, is inducibly expressed in enteric epithelial cells. These findings support the proposal that beta-defensins may contribute to host defense of enteric mucosa.

Amino Acid Sequence↗

Regeneration of graft liver in adult-to-adult living donor liver transplantation using a left lobe graft.

Graft size-matching is one of the critical concerns in adult-to-adult living donor liver transplantation (ATALDLT). In this study, we evaluated regeneration of a small-for-size graft less than 50% of the standard liver volume (SLV). We reviewed nine patients of united network of organ sharing (UNOS) status 2 or 3 who had undergone ATALDLT with a left lobe graft. For the comparison of liver regeneration, 20 hepatectomized patients for biliary malignancy were selected as non-transplant control group. In the ATALDLT group, graft size ranged from 30 to 49% of the SLV of recipients and their regeneration rates were 158%, 182%, 200% and 185% after 1,2, 3 and 4 weeks following transplantation, respectively. In the control group, preoperative volume of left lobe to whole liver volume ranged between 40 and 54% and their regeneration rates were 145%, 156%, 163% and 177% after 1,2, 3 and 4 weeks following extended right lobectomy, respectively. There was no statistical difference in regeneration rates between two groups. In the ATALDLT group, serum aspartate aminotransferase showed the median peak level of 198 IU/L on the first postoperative day and it was normalized within one week. Recovery of bilirubin clearance lagged behind rapid volume regeneration by about one week. Two patients died of sepsis. We postulate that the regenerative power of small-for-size grafts from living donors is preserved, although time-lag between volume regeneration and metabolic capability occurs in small-for-size grafts, when the initial graft volume meets metabolic demands during the early postoperative days.

Adult↗

Surgical pancreatic complications induced by L-asparaginase.

Pancreatitis has been noted to be a potential complication in 2% to 16% of patients undergoing treatment with L-asparaginase for a variety of pediatric neoplasms, but rarely has surgical intervention been necessary. The authors present two fulminant cases of L-asparaginase-induced pancreatitis and review the current literature. The first patient is a 15-year-old boy who underwent induction chemotherapy with L-asparaginase for non-Hodgkin's lymphoma with bone marrow involvement. He presented with diffuse patchy necrosis of the pancreas as well as a large infected pancreatic pseudocyst. He subsequently required operative debridement of the pancreas and external drainage of the pseudocyst. He is currently doing well. The second patient is a 5-year-old boy who was treated with L-asparaginase for a diagnosis of acute lymphocytic leukemia. Within 3 weeks of initiation of therapy, fulminant pancreatitis developed, which progressed to multisystem organ failure. Computed tomography scan demonstrated extensive pancreatic necrosis involving 90% of the gland. He underwent surgical debridement of his necrotic pancreas and wide drainage of the lesser sac. Postoperatively he improved but subsequently multiple complications developed including erosion of his gastroduodenal artery with significant intraabdominal bleeding, which was controlled with angiographic embolization. Subsequently erosion of his endotracheal tube into the innominate vein developed, and he died. L-asparaginase-induced pancreatitis has been described after therapy for various pediatric neoplasms, and the reported cases have usually been self-limiting. However, our cases demonstrate potentially fatal sequelae of this complication and mandate early diagnosis with appropriate surgical intervention in this setting.

Adolescent↗

Growth and development and other risk factors for osteosarcoma in children and young adults.

BACKGROUND: Risk factors for osteosarcoma in young people were investigated in a population-based case-control study among residents of New York State, excluding New York City. METHODS: Cases (n = 130) were diagnosed between 1978 and 1988 at < or = 24 years of age. Controls were randomly selected from birth certificates and were pair matched to cases on year of birth and sex. Exposure information was obtained by telephone interview with a subject and/or parent, and from birth certificates and school and medical records. RESULTS AND CONCLUSIONS: A significant positive association was observed with height one year before diagnosis (P-value for trend = 0.02). No significant associations were observed between osteosarcoma and weight of body mass index one year before diagnosis, birth length, birthweight, gestational age, having reached puberty, having begun growth spurt, age at puberty, age growth spurt began, medical x-rays, antenatal exposures, family history of cancer, birth defects, or parental occupation.

Adolescent↗

Human exposure to PCBS: modeling and assessment of environmental concentrations on the Akwesasne reservation.

The Mohawk Nation at Akwesasne, comprised of approximately 10,000 people, is located along the St. Lawrence River in upstate New York. The Akwesasne reservation has been contaminated by local industries, which are located on the St. Lawrence River and its tributaries, and by upstream sources on the Great Lakes. The closest known source of contamination to the reservation is General Motors (GM) Foundry, which is located less than 100 feet from the reservation's border. This facility is listed on the Environmental Protection Agency's National Priority List and the New York State's Department of Environmental Conservation's (NYSDEC) inactive hazardous waste disposal site list. Contamination to the reservation arising from discharge and secondary transport mechanisms has caused concern to the Mohawk people of Akwesasne. The characterization of the environment at Akwesasne required a historical review of existing environmental data, generation of a database, review of existing data, sampling to augment existing data, data analysis, data modeling and data generation based on a chosen model for all environmental pathways of interest. The objectives this work were to: 1) assess the quality of existing data, 2) create a database which will manage the over 6000 samples recorded taken from the local area, 3) augment the existing data with additional sampling, 4) determine the degradation or attenuation of PCBs and specific congeners in various environmental media over time, and 5) create a model that estimates environmental concentrations of PCBs retro- and pro-spectively for times that sampling had not occurred. The results of this process yielded concentrations of PCBs, congener specific and total, in several environmental medium. Modeling of environmental concentrations through a thirteen-year time period was performed for a fish, wildlife and surface soil. Other media were not modeled due to limited information or non-detectable concentrations reported in past work. Additionally, the study participants activity, consumption and residential information was considered when limiting this modeling effort. The results of this work were used to estimate environmental concentrations through time and space. The results of this work were extremely valuable when determining areas of concern and provided the basis for a detailed exposure assessment of 97 women who reside at the Reservation.

Animals↗

Transcription of tufA and other chloroplast-encoded genes is controlled by a circadian clock in Chlamydomonas.

Levels of mRNA for the chloroplast-encoded elongation factor Tu (tufA) showed a dramatic daily oscillation in the green alga Chlamydomonas reinhardtii, peaking once each day in the early light period. The oscillation of tufA mRNA levels continued in cells shifted to continuous light or continuous dark for at least 2-3 days. Run-off transcription analyses showed that the rate of tufA transcription also peaked early in the light period and, moreover, that this transcriptional oscillation continued in cells shifted to continuous conditions. The half-life of tufA mRNA was estimated at different times and found to vary considerably during a light-dark cycle but not in cells shifted to continuous light. Light-dark patterns of transcription of several other chloroplast-encoded genes were examined and also found to persist in cells shifted to continuous light or dark. These results indicate that a circadian clock controls the transcription of tufA and other chloroplast-encoded genes.

Animals↗

Simultaneous first-order and capacity-limited elimination kinetics after oral administration of verapamil.

In this study of the relationship between dose and plasma concentration of verapamil, controlled-release verapamil in doses of 120 mg, 180 mg, 360 mg, and 540 mg were examined. The 48 study subjects received verapamil daily during each of the 4 sequential 5-day dosing segments. Blood samples were collected frequently to obtain first-dose and steady-state (fifth dose) concentration profiles of verapamil. Plasma concentrations of R- and S-verapamil and R- and S-norverapamil were measured by stereospecific assay. Statistical comparisons of pharmacokinetic parameters and mean differences between doses were performed with analysis of variance models. At steady state, area under the concentration-time curve (AUC) values for R- and S-verapamil at both the 120-mg and 180-mg doses were about 1.5 times higher than the corresponding first-dose values. After both first and fifth doses, pharmacokinetic parameters for all four analytes were dose proportional between the 120-mg and 180-mg doses. A dose-proportional relationship also was found between the 360-mg and 540-mg dose levels. However, nonlinearity was found between the 180-mg dose and higher doses, suggesting saturable metabolic pathways. The dose-proportional relationship between the 360-mg and 540-mg doses suggests that other first-order metabolic pathways become dominant. Although results from this study are partially consistent with previously reported nonlinear verapamil kinetics, this is the first clinical study to demonstrate a dose-proportional relationship for verapamil at both low and high input rates (mg/hr). In addition, first-order disposition pathways of verapamil are probably nonexistent at medium input rates and become dominant at higher input rates.

Administration, Oral↗

Genetic mapping and embryonic expression of a novel, maternally transcribed gene Mem3.

To study the molecular function of genes expressed during preimplantation development, we isolated a novel maternal transcript SSEC (Stage Specific Embryonic cDNA)-26 from a partial subtraction library of mouse unfertilized eggs and preimplantation embryos. The SSEC-26 transcript is abundant in the unfertilized egg and also actively transcribed from the newly formed zygotic genome. On the basis of its expression in eggs and embryos, this new mouse gene is named Mem (maternal-embryonic) 3. The genomic locus of Mem3 has been mapped to Chromosome (Chr) 8 near the D8Mit78 marker and the glutaryl CoA dehydrogenase (Gcdh) locus. The deduced amino acid sequence of MEM3 resembles that of the yeast VPS (Vacuolar Protein Sorting) 35 in two separate domains. A cDNA sequence of the potential human homolog of Mem3 has been assembled with partial clones from the EST database and assigned to human Chr 16.

Amino Acid Sequence↗