Oral protein drug delivery.
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Administration, Oral↗
Biomedical subjects
W Wang
Publications and source records attributed to W Wang.
Theoretical studies of steady-state transcapillary exchange in countercurrent systems.
OBJECTIVE: As a first step in modeling microvascular exchange in the renal medulla, we developed mathematical models to explore the effects of blood flow, permeability, and anatomical arrangement of microvessels on the steady-state distribution of solute in the blood and the interstitial fluid (ISF). METHODS: Single capillaries and countercurrent capillary loops were used to model microvessels that were surrounded by a secretory epithelium over either the whole or part of the capillary length. Solute concentration in the vessels and the ISF were derived analytically. We also derived approximate solutions that ignored axial diffusion of solute. RESULTS: The full and approximate solutions were in good agreement with data based on measurements in the renal medulla. Model results revealed that concentration in the ISF falls rapidly with distance beyond the region of solute secretion and equilibrates with the concentration in capillaries, even with countercurrent exchange between the two limbs of the capillary loop. The ratio of the product of the permeability and area to the flow of the afferent limb, gamma 1, is an important parameter. When gamma 1 > 4, countercurrent exchange in a capillary loop facilitates a greater ISF concentration gradient than with a single capillary. Changes in flow also have a greater effect on this gradient. CONCLUSION: The model of countercurrent exchange presented here not only demonstrates the sensitivity of interstitial concentration gradients of solute to flow through capillary loops but also reveals the importance of the absolute value of gamma 1 in determining the magnitude and direction of these gradients.
Animals↗
Mechanisms for the hepatic uptake and biliary excretion of tributylmethylammonium: studies with rat liver plasma membrane vesicles.
Hepatic organic cation transport in vitro, using tetraethylammonium (TEA) as a substrate, consists of at least two steps: sinusoidal uptake is stimulated by an inside-negative membrane potential and canalicular membrane transport is mediated by organic cation:H+ exchange (Moseley et al., 1992b). In vivo, however, TEA is poorly excreted into bile. In contrast, larger, more hydrophobic organic cations, such as tributylmethylammonium (TBuMA), undergo significant hepatobiliary excretion. To better characterize hepatic organic cation transport, TBuMA transport was examined in rat canalicular liver plasma membrane (cLPM) and basolateral liver plasma membrane (bILPM) vesicles. In cLPM vesicles, under voltage-clamped conditions, an outwardly directed H+ gradient stimulated [3H]TBuMA uptake consistent with electroneutral TBuMA:H+ exchange; H(+)-dependent [3H]TBuMA uptake was not the result of a H+ diffusion potential. In the absence of a H+ gradient, intravesicular TBuMA trans-stimulated [3H]TBuMA uptake. Substrates for renal and hepatic organic cation:H+ exchange cis-inhibited H(+)-dependent [3H]TBuMA uptake. No ATP-dependent [3H]TBuMA uptake was detected in cLPM vesicles, and the P-glycoprotein substrate, daunomycin, did not cis-inhibit H(+)-dependent [3H]TBuMA uptake. Carrier-mediated [3H]TBuMA uptake exhibited saturability (Km of 0.5 mM and Vmax of 0.5 nmol/mg prot/5 s). In bILPM vesicles, in contrast, a valinomycin-induced intravesicular-negative K+ diffusion potential stimulated [3H]TBuMA uptake. These findings suggest that hepatic transport of TBuMA is similar to TEA but fundamentally different from that of P-glycoprotein substrates, indicating the involvement of at least two separate processes for the hepatobiliary excretion of organic cationic drugs.
Adenosine Triphosphate↗
Cognitive functioning and brain magnetic resonance imaging in children with sickle Cell disease. Neuropsychology Committee of the Cooperative Study of Sickle Cell Disease.
OBJECTIVE: Brain magnetic resonance imaging (MRI) and neuropsychological evaluations were conducted to determine whether neuroradiographic evidence of infarct in children with sickle cell disease between ages 6 and 12 years would result in impairment in cognitive and academic functioning. METHOD AND DESIGN: Children enrolled in the Cooperative Study of Sickle Cell Disease were evaluated with brain MRI and neuropsychological evaluation. Completed studies were obtained for 194 children, 135 with HbSS. MRIs were categorized according to the presence of T2-weighted, high-intensity images suggestive of infarct and were further categorized on the basis of a clinical history of cerebrovascular accident (CVA). An abnormal MRI but no clinical history of CVA was classified as a silent infarct. Neuropsychological evaluations included assessment of both global intellectual functioning and specific academic and neuropsychological functions. RESULTS: Central nervous system (CNS) abnormalities were identified on MRI in 17.9% of the children (22.2% of children homozygous for HbS), and a clinical history of CVA (N = 9, 4.6%) was identified in only children with HbSS disease. Subsequent analyses examined only children with HbSS. Children with a history of CVA performed significantly poorer than children with silent infarcts or no MRI abnormality on most neuropsychological evaluation measures. Children with silent infarcts on MRI performed significantly poorer than children with no MRI abnormality on tests of arithmetic, vocabulary, and visual motor speed and coordination. CONCLUSIONS: These results substantiate the importance of careful evaluation, educational planning, and medical intervention for CNS-related complications in children with sickle cell disease.
Anemia, Sickle Cell↗
Two deficiency cases of disputed paternity: sibling or half-sibling?
We report briefly the results of DNA analysis in two cases of disputed paternity where the alleged father and the mother were dead and only the children were available. In one case, half-sibship was established by minisatellite typing with a multi-locus probe and microsatellite FGA typing. In the other case, Y27H39 typing revealed that the fathers of the two male children were different. DNA polymorphisms, especially at microsatellite loci, provide useful information to solve such paternity cases.
Base Sequence↗
Microsatellite typing in a paternity case against a deceased man whose two brothers were available for testing.
To resolve a deficiency case of disputed paternity, we examined the mother, child, and two sibs of the deceased alleged father. In all of the 11 conventional marker systems and three microsatellite systems (ACTBP2, FGA, and D11S488) applied, the child and the paternal sibs had alleles is common. We deduced first the possible ACTBP2 genotypes of the deceased parents of the two sibs from their test results. Next, from all the combinations of the deduced genotypes, we estimated the frequencies of the possible genotypes of the alleged father and, with Bayes' theorem, calculated the probabilities of the alleged father having the genotypes compatible with paternity. Using these probabilities, we worked out the probability of the child's genotype resulting from the mating of the mother with the alleged father. Meanwhile, we calculated the probability of the child's genotype being expected of the mating of the mother with an unrelated random man. Finally, applying Bayes' theorem again, we obtained a probability of paternity of 0.992 for the ACTBP2 locus alone. Inclusion of the FGA locus in the probability calculations brought the overall probability of paternity to 0.998. The present study demonstrates that testing for hypervariable microsatellite loci greatly facilitates the solution of a deficiency case that would be difficult or time-consuming to solve by conventional marker typing.
Female↗
[Experiment on the rapid reproduction of Fritillaria taipaiensis P.Y. Li].
This paper reports the experimental results of rapid reproduction of Fritillaria taipaiensis by tissue culture. The research shows that the induction frequency of calluses and rebulbs with MS+NAA lmg/L+6BA 3mg/L is 93%. Fifteen kinds of common and trace elements that are necessary for human body are found in calluses and rebulbs. The contents of most elements obviously exceed those of cultural bulbs.
Calcium↗
[Anti-tumor effects of bispecific monoclonal antibody targeted human monocytes-macrophages on hepatoma cells].
OBJECTIVE: To study anti-tumor affects of bispecific monoclonal antibody targeted human monocytes-macrophages on hepatoma cells. METHODS: The fragment of monoclonal antibody HAb18F(ab')2 which has high affinity to hepatoma cells and the fragment of monoclonal antibody antimonocytes/macrophages MAb7F(ab')2 were cross-linked with N-succinimidyl 3-(2-pyridl-dithil) propionate. RESULTS: Heteroaggregated monoclonal antibodies HAb18F(ab')2-MAb7F(ab')2 could bind to hepatoma cells as well as monocytes-macrophages. They were purified with FPLC Sephacryl S-200. The bispecific character was identified with Indirect Immunofluorescent Staining. CONCLUSION: In vitro cytotoxicity assay showed that HAb18F(ab')2-MAb7F(ab')2 could significantly enhance the lysis of human hepatoma cells by human monocytes-macrophages.
Adenoma↗
[Modulation of bcl-2 antisense RNA on programmed cell death of leukemic cell line].
OBJECTIVE: To investigate modulation of decrease of intrinsic bcl-2 protein levels on programmed cell death of leukemia cells. METHOD: Gene transfection procedure was applied to observe the effect of antisense RNA-mediated suppression of bcl-2 gene expression on programmed cell death of human T-lymphocytic leukemia cell line CEM. RESULTS: Temporary expression of antisense bcl-2 gene could effectively reduce levels of intrinsic bcl-2 protein of CEM cells and render it more sensitive to etoposide-induced cytotoxicity. Moreover, a great deal of apoptotic bodies and ladder DNA was always produced during etoposide-mediated killing of CEM and when CEM expressing bcl-2 antisense RNA served as target cells in particular, the amount of ladder DNA increased to around 40%. CONCLUSION: Programmed cell death is one of the mechanisms by which etoposide kills leukemic cells and is modulated by cellular intrinsic bcl-2 protein.
Antineoplastic Agents, Phytogenic↗
Reaction of hydroxyl radical with phenylpropanoid glycosides from Pedicularis species: a pulse radiolysis study.
Using pulse radiolysis technique, the reaction between hydroxyl radical and 7 phenylpropanoid glycosides: echinacoside, verbascoside, leucosceptoside A, martynoside, pediculariosides A, M and N which were isolated from Pedicularis were examined. The rate constants of these reactions were determined by transient absorption spectra. All 7 phenylpropanoid glycosides react with hydroxyl radical at high rate constants within (0.97-1.91) x 10(10)L.mol-1.s-1, suggesting that they are effective hydroxyl radical scavengers. The results demonstrate that the numbers of phenolic hydroxyl groups of phenylpropanoid glycosides are directly related to their scavenging activities. The scavenging activities are likely related to o-dihydroxy group of phenylpropanoid glycosides as well.
Drugs, Chinese Herbal↗
Quintuplex PCR-amplification of microsatellites.
We tested the potential usefulness of quintuplex PCR-amplification of STRs (D16S537, D8S320, FGA, D11S554 and THO1) for paternity testing, first by constructing 20 false family trios, each with a non-biological father, to estimate the actual exclusion rate, and next by a retrospective study of 20 paternity cases which had been previously tested by RFLP analysis and typing of conventional genetic markers. The five STR loci have a combined average exclusion power of 99.8%. The forensic efficiency values for four of the five STRs were based on typing of a Japanese population of 300 individuals. The observed rate of exclusion was in close agreement with the expected rate for the Japanese population. In 12 of the 20 cases, paternity was not excludable by any of the loci. The probability of paternity calculated for the alleged father was > 99% in the inclusion cases. In the remaining 8 cases, paternity was excluded by at least 2 of the STR loci. The results of STR typing agreed with the data from RFLP analysis and conventional genetic typing. Taking advantage of five STRs sharing AA in the tetranucleotide repeats (AAAG or AATG), we detected PCR products simultaneously with a digoxigenin-labeled (AAAG)6 oligonucleotide probe after sequencing-gel electrophoresis. The quintuplex PCR-amplification of STRs is a rapid and efficient method for paternity testing and individual identification.
Base Sequence↗
DNA typing by triplex affinity capture (TAC) PCR.
Using a triplex affinity capture approach, we extracted PCR-ready DNA from fresh blood, buccal swabs, and bloodstains made on hard objects. We immobilized a biotinylated purine-rich oligonucleotide onto streptavidin-coated magnetic beads, and captured double-stranded DNA via triple-helix formation. We were able to amplify the MCT118, ACTBP2, FGA, D8S320, D11S488, and THO1 loci from the captured DNA. DNA typing by triplex affinity capture PCR is simple, rapid, and well-suited for paternity testing and population studies of microsatellites.
Base Sequence↗
[Genotypes of cystic fibrosis (CF) reported in the world and polymorphisms of cystic fibrosis transmembrane conductance regulator (CFTR) gene in Japanese].
Cystic fibrosis (CF) is a common autosomal recessive genetic disorder in Caucasians. Since identification of the gene responsible for CF in 1989, over 400 sequential alterations of the CFTR gene have been tabulated by the CF Genetic Analysis Consortium. However, except for the delta F508 mutation, which occurs in approximately 70% of CF chromosomes, the worldwide frequency of most mutations in this gene is less than 1%. In Orientals and African blacks, CF is very rare. In Japanese only 100 cases have been reported. A few genotypes of these cases have been analyzed but no delta F508 or other mutations were found. We have analyzed mutations of the CFTR gene in Japanese with diffuse panbronchiolitis (DPB), which is found only in Orientals and shares pathologic and clinical characteristics with mild adult CF. However, no significant mutation of the CFTR gene was identified in this series. This suggests a different etiological background from that of CF.
Asian People↗
Substrate and inhibitor specificity of glutamine cyclotransferase (QC).
This paper reports a systematic study of the substrate and inhibitor specificity of papaya latex glutamine cyclotransferase (QC). The results showed that the second amino acid residue in N-terminal glutaminyl peptides significantly accelerated papaya latex QC-catalyzed reactions while the third residue provided no further rate enhancement. Substrate binding was shown to be the main specificity-determining step. Fifteen proline derivatives and dipeptides containing an N-terminal proline were tested and found to inhibit papaya latex QC. This supports our previous molecular modeling study of the QC catalytic pathway which suggested a structure of the reaction intermediates similar to that of L-proline.
Acyltransferases↗
Production of monoclonal anti-thymine-dimer antibody and its use for detection of STR alleles.
To simplify the manual detection of STRs, we developed an immunoblotting method using an anti-thymine-dimer antibody. Upon ultraviolet irradiation, adjacent thymine residues in a DNA strand readily form thymine dimers which are detectable by anti-thymine-dimer antibody. We simply irradiated the supernatant of a boiled suspension of P3U1 myeloma cells with ultraviolet rays, and immunized BALB/c mice with it. By fusing their popliteal lymph node cells with the P3U1 myeloma cell line, we produced a monoclonal anti-thymine-dimer antibody. Using this antibody, we were able to detect STR alleles containing AAAG, AAGG, or AATG repeats by immunoblotting. Our method is well suited for use in parentage testing.
Alleles↗
Determination of sibship by microsatellite typing in a deficiency case of disputed maternity.
In a disputed maternity case where the father and his two wives were dead and only the six children were available for testing, we analyzed 24 conventional hemogenetic markers and 11 microsatellite (STR) loci. Putting all the results together, we were able to distinguish sibship from half-sibship. Of all the systems tested, STRs were most informative. The present study demonstrates the power of STRs as a tool for solving a deficiency case.
Alleles↗
Effects of an orally effective endothelin-A receptor antagonist in dogs with pacing-induced heart failure.
UNLABELLED: Endothelin-1 (ET-1) is a potent vasoconstrictor that has been shown to be elevated in the plasma of humans and animals with heart failure (HF). The role of an increase in endothelin in the setting of chronic HF is not known. METHODS: The present study was designed to determine the hemodynamic effects of a novel ET-A antagonist (PD-156,707) on the development of HF in dogs subjected to chronic ventricular tachycardia. Thirteen dogs were chronically instrumented to measure cardiac output (CO), left ventricular pressure (LVP), left atrial pressure (LAP), and arterial pressure (MAP). They were then paced at 210 bpm for 3 weeks and then at 245 bpm for 1 week (4th week). Two groups of dogs were studied, placebo group and a group of dogs administered the PD-156,707 compound (750 mg) orally three times per day beginning one day prior to the initiation of pacing. Hemodynamic measurements were made every three to four days during the four week pacing regimen. Arterial and venous blood samples were also taken to determine the plasma levels of endothelin-1 and PD-156-707. RESULTS: Endothelin-1 in plasma increased in all dogs with pacing induced HF (placebo control 1.57 +/- 0.5 vs placebo HF 2.2 +/- 0.6 pg/ml and drug control 1.5 +/- 0.16 v.s. drug HF 14.6 +/- 3.8 pg/ml [p < 0.05]). Left ventricular end diastolic pressure (LVEDP) and LAP were equivalently and significantly elevated in both groups (p < 0.001) and LV dp/dt was significantly reduced (p < 0.001) in both groups 4 weeks after pacing. CO was slightly, but not significantly reduced after four weeks in both groups of dogs. However, administration of PD-157,707 significantly and profoundly reduced MAP at all times after 3 days of pacing (placebo HF[week 4]: 83.9 +/- 4.0 mmHg v.s. drug HF [week 4]: 72.4 +/- 2.3 mmHg [p < 0.05]) and total peripheral resistance (p < 0.05) at each time period following the induction of pacing. CONCLUSION: These data indicate that ETA blockade reduces afterload early during the development of chronic HF implicating endothelin-1 as an early compensatory hormone in HF. These results also suggest that blocking the ET-A receptor may have a role as an afterload reducer in the setting of human congestive heart failure.
Administration, Oral↗
STR typing of buccal swabs for paternity testing with reference to Japanese population data on the D20S85, D14S118, and D14S543 loci.
To simplify short tandem repeat (STR) typing of genomic DNA, we used buccal cells instead of blood cells. Buccal swabs taken from paternity-test trios were washed with 1 ml of distilled water by centrifugation, and the pellets were suspended in 20 microliters of distilled water. The suspensions were frozen at -80 degrees C and then thawed. Using a 1/5 volume of each suspension, we were able to type STRs at the TH01, D20S85, D14S118, and D14S543 loci by triplex PCR amplification of the first three markers and by simplex amplification of the other. In addition, we studied the polymorphisms at the D20S85, D14S118, and D14S543 loci in a Japanese population of 320 individuals. The four loci have a combined average exclusion power of 99.37%. In 24 cases of disputed paternity, the results of STR typing of the four loci agreed with those of conventional marker typing. In addition to being simple and rapid, STR typing of buccal swabs involves no painful procedure. It is therefore preferable for paternity tests on infants and small children.
Alleles↗