Biomedical subjects
Publications and source records attributed to J Ahn.
A terahertz half-cycle pulse was used to retrieve information stored as quantum phase in an N-state Rydberg atom data register. The register was prepared as a wave packet with one state phase reversed from the others (the "marked bit"). A half-cycle pulse then drove a significant portion of the electron probability into the flipped state via multimode interference.
A gene for reading disability has been localized by nonparametric linkage to 6p21.3-p22 in several published reports. However, the lack of an uninterrupted genomic clone contig has made it difficult to determine accurate intermarker distances, precise marker order, and genetic boundaries and hinders direct comparisons of linkage. The search and discovery of the hemochromatosis gene (HFE) led to the creation of a bacterial artificial chromosome (BAC) and P-1 derived artificial chromosome (PAC) contig that extended physical maps 4 Mb from the MHC toward pter and localized new markers in that region [10-12]. Using this contig, we localized 124 sequence tagged sites, expressed sequence tags, and short tandem repeats including most of the markers in linkage with reading disability phenotypes, succinic semialdehyde dehydrogenase, GPLD1, prolactin, and 18 uncharacterized genes. This new contig joins and extends previously published physical maps to span the entire chromosome 6 reading disability genetic locus. Physical mapping data from the complete contig show overlap of the published linkage peaks for reading disability, provide accurate intermarker distances and order, and offer resources for generating additional markers and candidate genes for high resolution genetic studies in this region.
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We isolated cDNA encoding turkey inhibin-alpha (tINH-alpha) and -betaA (tINH-betaA) subunits from the turkey ovary using reverse transcription-polymerase chain reaction (RT-PCR). The isolated alpha subunit and betaA subunit included the entire open reading frames encoding 329 and 424 amino acids, respectively. The amino acid sequences of mature tINH-alpha subunit and tINH-betaA subunit (12.6 and 12.9 kDa proteins, respectively), established via DNA sequence analysis, were highly conserved between the chicken and various mammals. Northern blot analysis revealed that the transcripts of tINH-alpha and tINH-betaA subunits were approximately 1.7 and 8.4 kb, respectively. In various stages of follicular development, tINH-alpha mRNA was highly expressed in small white follicles as compared to postovulatory and regressed follicles, whereas tINH-betaA mRNA was predominately expressed in preovulatory F5 follicles.
The hypothesis for the present study is that the active immunization of female turkeys with inhibin (INH) would neutralize endogenous INH, and increase levels of circulating follicle stimulating hormone (FSH) and the number of preovulatory follicles, and subsequently enhance egg production. Two experiments were conducted with female turkeys in their first (30 wk of age) and second (62 wk of age) laying cycles. Treatment groups included control turkeys immunized with keyhole limpet hemocyanine (KLH) and experimental turkeys immunized with recombinant turkey inhibin alpha conjugated to KLH (rtINH), vasoactive intestinal peptide (VIP) conjugated to KLH or rtINH+VIP. Egg production increased (P < 0.05) in VIP and rtINH+VIP immunized birds, but not in rtINH immunized hens in comparison with a control group. A similar number of ovarian follicles, arranged in the follicular hierarchy of laying hens, was observed in all experimental groups. However, there was a larger number of nongraded yellow follicles in rtINH-immunized (62.5%) and rtINH+VIP-immunized (73.5%) groups compared with that of controls, suggesting overstimulation by FSH. Anterior pituitary FSH beta subunit, LH beta subunit, and prolactin (PRL) mRNA contents were determined by Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) in laying hens at the end of the experimental period. Hens immunized with rtINH showed increased FSH beta subunit mRNA content, but no change in the content of LH beta subunit or PRL mRNA. Hens immunized with VIP or rtINH+VIP had significant increases in both pituitary LH beta subunit and FSH beta subunit mRNA contents, accompanied by a decline in PRL mRNA abundance. The magnitude of the increase in FSH beta subunit to INH immunoneutralization was greater in first-cycle hens than in second-cycle hens. These data suggest that active immunization of female turkeys with INH neutralizes endogenous INH and increases both circulating FSH and the number of preovulatory follicles. However, no significant increase in egg production was observed in INH-immunized hens. The data confirm previous reports that VIP immunoneutralization increases egg production in turkey hens and shows for the first time that it also increases FSH beta subunit and LH beta subunit gene expression.
Surface acoustic wave (SAW) reflection from diamond-like carbon (DLC) strip reflecting arrays on Y-Z LiNbO3 is investigated. The reflection from DLC strips with triangular cross section has been observed. Reflection increases in alternating DLC and Al strips in 90 degrees reflecting arrays in comparison with pure Al structures. The values of reflection coefficient per period in the slanted reflecting arrays are estimated to be about 1.0% for pure DLC strips (height to wavelength ratio equal to 0.02), 2% for uniform Al coating on DLC reflecting arrays, and 3.5% for alternating DLC and Al strips. This value is higher than that for pure Al strips by about 0.7%. Reflection properties are briefly discussed, and preparation technique is presented.
The p53 protein is related by sequence homology and function to the products of two other genes, p63 and p73, that each encode several isoforms. We and others have discovered previously that certain tumor-derived mutants of p53 can associate and inhibit transcriptional activation by the alpha and beta isoforms of p73. In this study we have extended these observations to show that in transfected cells a number of mutant p53 proteins could bind and down-regulate several isoforms not only of p73 (p73 alpha, -beta, -gamma, and -delta) but also of p63 (p63 alpha and -gamma; Delta Np63 alpha and -gamma). Moreover, a correlation existed between the efficiency of p53 binding and the inhibition of p63 or p73 function. We also found that wild-type p63 and p73 interact efficiently with each other when coexpressed in mammalian cells. The interaction between p53 mutants and p63 or p73 was confirmed in a physiological setting by examining tumor cell lines that endogenously express these proteins. We also demonstrated that purified p53 and p73 proteins interact directly and that the p53 core domain, but not the tetramerization domain, mediates this interaction. Using a monoclonal antibody (PAb240) that recognizes an epitope within the core domain of a subset of p53 mutants, we found a correlation between the ability of p53 proteins to be immunoprecipitated by this antibody and their ability to interact with p73 or p63 in vitro and in transfected cells. Based on these results and those of others, we propose that interactions between the members of the p53 family are likely to be widespread and may account in some cases for the ability of tumor-derived p53 mutants to promote tumorigenesis.
Fourteen-day adrenal steroid treatment increases [(3)H]ouabain binding sites 22-48% in muscle biopsies from patients treated with adrenal steroids for chronic obstructive lung disease and in rats treated with dexamethasone (Dex). Ouabain binding measures plasma membrane sodium pumps (Na(+)-K(+)-ATPase) with isoform-dependent affinity. In this study we have established the specific pattern of Dex regulation of sodium pump isoform protein and mRNA levels in muscle. Rats were infused with Dex (0.1 mg/kg per day) or vehicle for 14 days. Abundance of sodium pump catalytic alpha(1)- and alpha(2)-subunits and glycoprotein beta(1)- and beta(2)-subunits was determined by immunoblot in soleus, extensor digitorum longus, whole gastrocnemius, and diaphragm and was normalized to the mean vehicle control value. Dex increased alpha(2) and beta(1) protein in all muscle types by 53-78% and ~50%, respectively. Dex increased alpha(1) protein only in diaphragm (65 +/- 7%). At the mRNA level in whole hindlimb muscle, Dex increased alpha(2) (6.4 +/- 0.5-fold) and beta(1) (1.54 +/- 0.15-fold) and decreased beta(2) (to 0.36 +/- 0.6 of control). In summary, alpha(2)beta(1) is the Dex-responsive pump in all skeletal muscles, and changes in alpha(2) and beta(1) mRNA levels can drive the 50% change in alpha(2)beta(1)-subunits, which can account for the reported increase in [(3)H]ouabain binding.
The effects of various types of electron acceptors on anoxic phosphorus uptake were investigated in detail to obtain a better insight into the metabolic behavior of denitrifying phosphate-accumulating organisms. Batch experimental tests under three different electron acceptor conditions, i.e., nitrate, nitrite and mixtures of nitrate and nitrite, were carried out using activated sludge cultivated in a sequencing batch reactor. The experimental results confirmed no inhibition of the utilization of nitrate or nitrite as an electron acceptor for anoxic phosphorus uptake. Anoxic phosphorus uptake occurred provided there was an electron acceptor present regardless of whether it was nitrate or nitrite. However, for nitrite a relatively small amount of anoxic phosphorus was taken up per nitrogen denitrified compared to nitrate. On the other hand, the amount of anoxic phosphorus taken up per nitrogen denitrified increased with an increase in the initial loading amount of electron acceptor in the case of nitrate, whereas it slightly decreased nitrite. Moreover, the amount of phosphorus taken up per nitrogen denitrified decreased with increasing mixed liquor suspended solid (MLSS) concentration in the case of nitrate, while it slightly increased for nitrite. From these results, it was confirmed that the activity of anoxic phosphorus uptake is strongly associated with the type and the initial loading amount of electron acceptor and the MLSS concentration under anoxic conditions.
OBJECTIVES: The primary objective of this study was to determine if a selected sample of pharmacists who had attended a chemical dependency training program were performing more chemical dependency related activities than a group of American Pharmaceutical Association (APhA) members who had not had this training. Additionally, an assessment of the perceived barriers to performing chemical dependencyrelated activities was performed. DESIGN: A confidential mail questionnaire was sent to 305 Utah School participants and 305 APhA members who had not participated in the program (See Appendix). RESULTS: Respondents who had received educational training in chemical dependency were more likely to perform the following activities: lecture to community groups and health care professionals about chemical dependency, participate in a pharmacists' recovery program, provide patients with information about treatment centers, and counsel patients about the alcohol in over-the-counter products. Respondents who had not received chemical dependency training indicated that the following barriers prevented them from taking a more active role in the chemical dependency field: lack of knowledge of chemical dependency resources in the community, unaware of how to get involved with the state recovery program, belief that involvement in the state recovery program would hurt their professional reputation, belief that chemically dependent individuals cannot be rehabilitated, and uncomfortable working with chemically dependent patients. CONCLUSIONS: Pharmacists who have attended substance abuse training programs are performing more chemical dependency activities than pharmacists who have not received training in chemical dependency. In addition, different barriers to performing chemical dependency related activities exist between pharmacists with and without training in this field.
The present study was carried out to find an appropriate coating material to microencapsulate lactase and the conditions under which it could be used. As a coating material, medium-chain triacylglycerol (MCT) and polyglycerol monostearate (PGMS) were superior. Three different percentages of microcapsules (2, 4, and 6%) were added and subdivided into three groups by washing time (0, 1, and 2). The highest efficiency of microencapsulation was found in the ratio of 15:1 as coating to core material with both MCT (94.9%) and PGMS (72.8%). Lactose content was not significantly changed up to 12 d with MCT and up to 8 d with PGMS with 2% of twice washed microcapsule addition. Also, sweetness was not significantly increased in storage compared with that of market milk. The present study provides evidence that emulsifiers can be used as an effective coating material to microencapsulate lactase. In addition, these results suggest that acceptable milk products can be prepared with microencapsulated lactase.
omega6 and omega3 fatty acids are important cellular components and known to be involved in disease processes. However, few studies have focused on mucosa fatty acid in human gastric cancer. The purpose of this study was to investigate how fatty acid patterns of mucosa are altered in gastric cancer. Fatty acids were analyzed by gas chromatography and their relative compositions (%) were determined and evaluated both in mucosa total-fatty acids and in phospholipid-fatty acids in paired cancerous and non-cancerous gastric cancer tissues (n = 18). The level of arachidonic acid (20:4omega6, AA) appeared significantly higher both in phospholipid-fatty acids (p < 0.05) and in total-fatty acids (p < 0.001) in cancerous mucosa compared to non-cancerous mucosa. The omega6/omega3 fatty acid ratio of phospholipid-fatty acids was also significantly higher in cancerous mucosa. The higher level of AA in cancerous tissue can be partially explained by the higher ratio of 20:4omega 6/20:3omega6 (desaturation index) and the lower ratio of 22:4omega6/20:4 omega6 (elongation index). The change in the relative composition of arachidonic acid may influence the production of prostaglandins and related metabolites, which regulate cell differentiation and proliferation. The findings of this study with respect to fatty acid changes, especially in terms of arachidonic acid metabolism, may be of relevance in the understanding of the roles of specific fatty acids and possibly of eicosanoids in gastric cancer.
Although little is known on the function of gammadelta T lymphocytes, there is increasing evidence that gammadelta T lymphocytes are early responders and modulators of immune responses against pathogens and cytokines such as IL-2, IL-7, IL-15 and TNF-a. To study the role TNF-a on gammadelta T lymphocytes, we cloned bovine TNF-a. Sequence analysis revealed that a new allele form of bovine TNF-a was cloned which has 3 additional nucleotide sequences as well as 3 nucleotide substitutions compared with previously reported bovine TNF-a. Further studies are needed to document the functional significance of a new allele form of TNF-a in cattle.
It is important to gain insight into p53 DNA binding and how it is regulated. By using electrophoretic mobility shift assays and DNase I footprinting, we show that a region within the N terminus of the protein controls the dissociation of p53 from a p53-binding site. When p53 is bound by a number of N-terminal-specific monoclonal antibodies, its rate of dissociation from DNA is reduced, and its ability to protect a cognate site from DNase I digestion is increased. Moreover, greatly reduced dissociation is observed with p53 protein lacking the N-terminal 96 amino acids. By contrast, deletion of the C terminus does not affect p53 dissociation from DNA or DNase I protection. p53 protein expressed in and purified from bacterial cells displays markedly more instability on its consensus DNA-binding site than does p53 produced in insect cells, suggesting that post-translational modifications may affect the stability of the protein. Our results provide evidence that the N terminus of p53 possesses an auto-inhibitory function that is mechanistically different from the inhibitory region at the C terminus.
YKL-1, E1B 55 kDa-deleted recombinant adenovirus vector, capable of harboring a transgene casette of up to 4.9 kb, was newly constructed by reintroducing E1A and E1B 19 kDa into E1/E3-deleted adenoviral vector with a homologous recombination in E. coli. Virus replication and cytotoxicity were dramatically attenuated in all 3 different types of normal human cells. In contrast, YKL-1 efficiently replicated and induced cytotoxicity in most cancer cells, especially Hep3B and C33A cells with an inactivating p53 mutation. However, both H460 and HepG2 exhibited intermediate sensitivity to YKL-1, which was between that of Hep3B or C33A and normal human cells. The YKL-1 and DNA damaging agent, camptothecin effectively induced p53 in H460 and HepG2 as well as in normal cells. Furthermore, YKL-1 effectively prohibited both Hep3B and C33A tumor growth in nu/nu mice in a dose-dependent manner. H/E staining and TUNEL assay indicated a largely distributed necrotic area and apoptosis on its periphery. This study, therefore, indicates that YKL-1, possesses promising potential as an oncolytic adenoviral vector, which acts partially in a p53-dependent manner.
ABCR is a photoreceptor-specific ATP-binding cassette transporter that has been linked to various retinal diseases, including Stargardt macular dystrophy, and implicated in retinal transport across rod outer segment (ROS) membranes. We have examined the ATPase and GTPase activity of detergent-solubilized and reconstituted ABCR. 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonic acid-solubilized ABCR had ATPase and GTPase activity (K(m) approximately 75 micrometer V(max) approximately 200 nmol/min/mg) that was stimulated 1.5-2-fold by all-trans-retinal and dependent on phospholipid and dithiothreitol. The K(m) for ATP decreased to approximately 25 micrometer after reconstitution, whereas the V(max) was strongly dependent on the lipid used for reconstitution. ABCR reconstituted in ROS phospholipid had a V(max) for basal and retinal activated ATPase activity that was 4-6 times higher than for ABCR in soybean or brain phospholipid. This enhanced activity was mainly due to the high phosphatidylethanolamine (PE) content of ROS membranes. PE was also required for retinoid-stimulated ATPase activity. ATPase activity of ABCR was stimulated by the addition of N-retinylidene-PE but not the reduced derivative, retinyl-PE. ABCR expressed in COS-1 cells also exhibited retinal-stimulated ATPase activity similar to that of the native protein. These results support the view that ABCR is an active retinoid transporter, the nucleotidase activity of which is strongly influenced by its lipid environment.
BACKGROUND: Sickle cell intrahepatic cholestasis is a potentially catastrophic complication of sickle cell anemia Once acute liver failure develops, transplantation is the only option. We describe a patient with sickle cell intrahepatic cholestasis who underwent liver transplantation. METHODS: Data were obtained from the chart. Serial hemoglobin S levels were monitored, and measures were taken to maintain hemoglobin S <20% to prevent sickle cell crisis. RESULTS: Although the allograft functioned well initially, the patient developed veno-occlusive disease and required repeat transplantation at 5 months after transplant. Histologic examination of the explant revealed occlusion of the terminal hepatic venules due to fibrosis and packed red cells. Repeat transplant was complicated by thrombosis of the intrahepatic portion of the hepatic artery, and sepsis. The patient died of sepsis after a third transplant. CONCLUSION: Liver transplantation for sickle cell disease involving the liver may carry a high risk of graft loss due to vascular problems. Repeat transplantation may not be feasible if disease recurs.