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Biomedical subjects

K Yu

Publications and source records attributed to K Yu.

159 records · Page 9Linked to original sources
PubMed1983

5-Fluorouracil + Oncovin + Adriamycin + mitomycin C (FOAM): an effective program for breast cancer, even for disease refractory to previous chemotherapy. A Northern California Oncology Group (NCOG) Study.

One hundred and thirty-one patients (118 evaluable) with disseminated breast cancer were treated with a combination of 5-fluorouracil + Oncovin + Adriamycin + mitomycin C (FOAM). The objective response rate for 82 evaluable patients whose disease was refractory to previous CMF or L-PAM chemotherapy was 35%; that for 36 evaluable patients who had not previously received chemotherapy, 56%. The hematologic toxicity of this therapy was generally mild and acceptable. It is believed that FOAM is an effective therapy for patients whose tumors are resistant to CMF.

Adult↗
PubMed1976

DNA synthesis in polyoma virus infection. IV. Mechanism of formation of closed-circular viral DNA deficient in superhelical turns.

A marked reduction in the rate of viral DNA synthesis is accompanied by an alteration to the superhelicity of progeny DNA in polyoma virus-infected cells in which protein synthesis has been inhibited by cycloheximide. Viral DNA molecules formed in the presence of cycloheximide consist predominantly of closed-circular monometric species (referred to as form Ic) characterized by a decreased superhelix density, corresponding to deltasigmao = 0.0195, as compared to form I DNA by propidium diiodide-cesium chloride isopycnic analysis. Form Ic is synthesized on pre-existing form I templates without the intervention of progeny form I as an intermediate. It is concluded that inhibition of protein synthesis results in the alteration of some process in the closure of daughter DNA that leads to a marked reduction of superhelical turns of progeny molecules. About two-thirds of form Ic molecules return to the form I conformation upon reversal of cycloheximide inhibition by a mechanism independent of DNA replication.

DNA Replication↗
PubMed1976

DNA synthesis in polyoma virus infection. V. Kinetic evidence for two requirements for protein synthesis during viral DNA replication.

Protein synthesis in polyoma virus-infected cells was inhibited by 99% within 4 min after exposure to 10 mug of cycloheximide per ml. Subsequent to the block in protein synthesis, the rate of viral DNA synthesis declined via inhibition of the rate of initiation of new rounds of genome replication (Yu and Cheevers, 1976). This process was inhibited with complex kinetics: within 15 min after the addition of cycloheximide, the rate of formation of closed-circular viral DNA was reduced by about one-half. Thereafter, DNA synthesis in cycloheximide-treated cells declined more slowly, reaching a level of 10% of untreated cells only after approximately 2 h. Protein synthesis was also required for normal closure of progeny form I DNA: in the presence of cycloheximide, DNA synthesis was diverted from the production of form I to form Ic, a monomeric closed-circular DNA component deficient in superhelical turns (Yu and Cheevers, 1976). Form I is replaced by Ic with first-order exponential kinetics. It is concluded that at least two proteins are involved in the control of polyoma DNA replication. One is apparently a stoichiometric requirement involved in the initiation step of viral DNA synthesis, since this process cannot be maintained at a normal rate for more than a few minutes in the absence of protein synthesis. The second protein requirement, governing the closure of newly synthesized progeny DNA, is considered distinct from the "initiation" protein on the basis of the kinetic data.

Cycloheximide↗
PubMed1975

DNA synthesis in polyoma virus infection. III. Mechanism of inhibition of viral DNA replication by cycloheximide.

The formation of viral DNA was inhibited in polyoma virus-infected cells in which protein synthesis had been blocked by cycloheximide. The present studies show the following. (i) The pool of replicating viral DNA molecules was reduced in cycloheximide-treated cells by an amount consistent with inhibition of [3-H]thymidine incorporation into viral DNA, whereas the rate of turnover of the replicating population was not affected. (ii) The rate of conversion of replicating molecules into closed-circular DNA was not affected by cycloheximide. (iii) The rate of elongation of nascent viral DNA fragments into strands of unit genome length was unaffected by cycloheximide. It is concluded that viral DNA synthesis is inhibited in the absence of protein synthesis exclusively at the level of initiation of new rounds of genome replication. Replicating molecules already initiated at the time of addition of cycloheximide matured into progeny closed-circular DNA at a normal rate.

Animals↗
PubMedDate not supplied

Contrast media for cardiothoracic MR imaging.

Contrast media have been used for the study of disease of the thorax. Most experience has consisted of the use of MR contrast media for improving the delineation of acute myocardial infarction, for demarcating the area of acute myocardial ischemia, and for demonstrating the area of potentially jeopardized myocardium after acute coronary occlusion. Contrast agents demonstrate the ischemic or jeopardized area as a zone of decreased signal intensity to normal myocardium. On the other hand, the magnetic susceptibility agents demonstrate the ischemic or jeopardized area as a zone of increased signal intensity to normal myocardium. Little experience exists concerning the use of MR contrast media for enhancing mediastinal and lung masses. The few reports to date demonstrate that contrast media can improve the conspicuity of thoracic masses. A new nonionic contrast medium, gadodiamide injection, has been shown to considerably increase S/N and C/N of thoracic masses. Further studies are necessary to define the role of MR contrast media in the evaluation of myocardial ischemia and thoracic masses in clinical practice.

Animals↗
PubMedDate not supplied

Expectancies and other psychosocial factors associated with alcohol use among early adolescent boys and girls.

Early experimentation with drinking increases the lifetime risk for substance abuse and other serious health and social problems. We studied factors associated with early alcohol experimentation by surveying 4,263 sixth- to eighth-grade students (67.1% White, 23.5% Black, 7.2% other races combined; 2.2% missing data) from seven schools in one suburban school district. The prevalence of drinking in the last 30 days was 12.1% for boys and 13.1% for girls (12.6% overall); 6.6% among sixth graders, 11.1% among seventh graders, and 19.5% among eighth graders. In multiple logistic regression analyses, controlling for grade, positive alcohol expectancies, perceived prevalence, and deviance acceptance were associated positively, self-control negatively, with drinking for both boys and girls. Among boys, grade point average was negatively associated with drinking. Among girls, propensity for risk-taking and problem-behaving friends were positively associated and high parental expectations were negatively associated with drinking. Alcohol use in our sample of early adolescent boys and girls was better explained by modifiable psychosocial factors such as alcohol expectancies, perceived prevalence, and self-control than by grade.

Adolescent↗
PubMedDate not supplied

Synthesis of stable hydrazones of a hydrazinonicotinyl-modified peptide for the preparation of 99mTc-labeled radiopharmaceuticals.

Hydrazones of a 6-hydrazinonicotinyl-modified cyclic peptide IIb/IIIa receptor antagonist were prepared in order to protect the hydrazine moiety from reaction with trace aldehyde and ketone impurities encountered during the process of manufacturing and compounding lyophilized kits used in radiolabeling with (99m)Tc. Hydrazones were prepared by either a direct reaction of the 6-hydrazinonicotinyl-modified cyclic peptide with carbonyl compounds or by conjugation of the cyclic peptide with hydrazones of succinimidyl 6-hydrazinonicotinate. Stability of the hydrazones was evaluated by treatment with formaldehyde. Hydrazones derived from simple aliphatic aldehydes underwent an exchange reaction with formaldehyde, while hydrazones of aromatic aldehydes and ketones provided the greatest level of stability when challenged with formaldehyde. We have been successful in protecting 6-hydrazinonicotinyl-modified cyclic peptides from reacting with formaldehyde, while still allowing sufficient reactivity for radiolabeling with (99m)Tc. The hydrazones of succinimidyl 6-hydrazinonicotinate are convenient and general reagents for forming 6-hydrazinonicotinyl conjugates with amino-functionalized bioactive molecules.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

A follow-up survey of alcohol consumption and knowledge in medical students.

We surveyed a medical school's students' drinking habits and knowledge 12 years after a previous survey. In this current survey from two academic years, final year students drank less than second year students did. Women in their second year drank as much as men. Overall, 28% of students drank more than the safe limits; 27% of students were problem drinkers, as measured by the CAGE questionnaire, and 52%, as measured by the AUDIT questionnaire. The proportion of students not drinking any alcohol rose from 6% in the previous survey to 27% in the current survey, possibly due to context and demographic changes. In spite of this difference, there have been no statistically significant reductions in either unsafe drinking levels or CAGE scores over 12 years. A third of students overestimated the safe levels of drinking. All medical schools should write and implement an alcohol policy.

Adult↗
PubMedDate not supplied

Integration of simple sequence repeat (SSR) markers into a molecular linkage map of common bean (Phaseolus vulgaris L.).

Microsatellite or simple sequence repeat (SSR) markers have been successfully used for genomic mapping, DNA fingerprinting, and marker-assisted selection in many plant species. Here we report the first successful assignment of 15 SSR markers to the Phaseolus vulgaris molecular linkage map. A total of 37 SSR primer pairs were developed and tested for amplification and product-length polymorphism with BAT93 and Jalo EEP558, the parental lines of an F7 recombinant inbred (RI) population previously used for the construction of a common bean molecular linkage map. Sixteen of the SSRs polymorphic to the parental lines were analyzed for segregation and 15 of them were assigned to seven different linkage groups, indicating a widespread distribution throughout the bean genome. Map positions for genes coding for DNAJ-like protein, pathogenesis-related protein 3, plastid-located glutamine synthetase, endochitinase, sn-glycerol-3 phosphate acyltransferase, NADP-dependent malic enzyme, and protein kinase were determined for the first time. Addition of three SSR loci to linkage group B4 brought two separated smaller linkage groups together to form a larger linkage group. Analysis of allele segregation in the F7 RI population revealed that all 16 SSRs segregated in the expected 1:1 ratio. These SSR markers were stable and easy to assay by polymerase chain reaction (PCR). They should be useful markers for genetic mapping, genotype identification, and marker-assisted selection of common beans.

Alleles↗
PubMedDate not supplied

Mapping genes conferring resistance to Phytophthora root rot of soybean, Rps1a and Rps7.

A linkage map was constructed for two Phytophthora sojae Kauf. +Gerd. root rot resistance genes, Rps1a and Rps7, in soybean (Glycine max (L.) Merr.) using microsatellite or simple sequence repeat (SSR) markers. An F2 population consisting of 81 individuals derived from a cross between OX281, which carries Rps7, and Mukden, which carries Rps1a, was used as the mapping population. A linkage map consisting of 10 SSR markers was first constructed using the computer software MapMaker/EXP 3.0. Rps1a and Rps7 were then placed at two different loci in the same linkage group with LOD scores of 2.88 and 9.16, respectively. Rps1a and Rps7 were linked at a distance of 13.8 cM. Rps1a was flanked by Satt159 (0.7 cM) and Satt009 (3.2 cM). Rps7 was flanked by Satt009 (10.6 cM) and Satt125 (29.1 cM).

Chromosome Mapping↗
PubMedDate not supplied

Pharmacokinetics of ipriflavone and metabolites after oral administration of a corn-oil suspension relative to the Osteofix tablet.

Ipriflavone (IP) is a derivative of naturally occurring isoflavones and is marketed as Osteofix for the treatment of osteoporosis in Europe. IP has poor aqueous solubility, and the Osteofix compressed tablet has poor and variable bioavailability (F ). IP is incompletely absorbed after oral administration and is converted to five major metabolites (M1, M2, M3, M4, and M5). It is also further converted to metabolites M6 and M7 to a very small extent. The metabolites, especially M2 and M5, also have activity. A pilot study was conducted in healthy male volunteers that showed an 8- to 20-fold increase in the IP bioavailability after administration of Osteofix tablets in the fed state relative to the fasting state. A four-way crossover study was conducted in 16 healthy male volunteers, receiving Osteofix in fed state and 50, 100, and 200 mg of IP corn-oil suspension in fasted state. All IP administrations were safe and well tolerated. There was a reduction in the IP plasma level variability after 100-mg corn-oil administration as compared with that for the tablet. There was an increased relative F after the suspension, which was such that the 50-mg IP corn-oil suspension yielded similar levels as the 200-mg tablet. M5 was the major metabolite, consistent with earlier reports. The area under the curve to the last measured time point (AUC ( t ) ) levels were lower for M5, M3, and M2; higher for M1 and M2; and similar for IP after 50-mg corn-oil administration, as compared with the values for the tablet. This result may partially be explained by differences in the half-lives. Absorption/formation of M2 was delayed. The metabolite formation, except for M1 and M5, decreased with increased doses, which was accompanied by the prolonged half-life of IP and nonproportional increase in the IP AUC ( t ). This result may be due to autoinhibition of IP metabolism, because IP is an inhibitor of CYP3A4, and the metabolism of IP may be partly CYP3A4 mediated. Osteofix F may be improved by formulations that increase solubility, such as the corn-oil suspension. Although equivalent IP exposure from the tablet may be achieved at much lower overall doses because of the improved F by the corn-oil suspension, higher doses may require reconfirmation of safety and efficacy, given the differences in metabolic profiles obtained at higher doses.

Administration, Oral↗
PubMedDate not supplied

Association of hyaluronidase and breast adenocarcinoma invasiveness.

Hyaluronic acid (HA) is a component of the extracellular matrix (ECM) that exists as a high molecular weight polymer composed of alternating disaccharides, D-glucuronic acid and N-acetyl D-glucosamine. The interaction of hyaluronidase with HA results in the disruption of basement membrane integrity and produces an angiogenic response that has been implicated in tumor invasiveness and metastasis. Although hyaluronidase is present in several neoplasms, levels of hyaluronidase expression in breast cancer are not known. This investigation defines the correlation of elevated levels of hyaluronidase with breast adenocarcinoma invasiveness. Utilizing RT-PCR, RNA was extracted from paraffin embedded tissues (n=6) of patients diagnosed with fibrocystic breast changes, ductal carcinoma in situ (DCIS), and invasive adenocarcinoma. After constructing cDNA primers for base pairs 504 and 759 of the PH-20 gene (which is homologous to the hyaluronidase gene), PCR was performed and the products were visualized with ethidium bromide using gel electrophoresis. Invasive breast adenocarcinoma had a significantly higher level of hyaluronidase expression compared to other breast tissue samples; (32+/-15 vs. 8+/-3; p<0.03). Elevated levels of hyaluronidase correlated with invasive breast adenocarcinoma. Our data suggests that elevated levels of hyaluronidase are associated with breast adenocarcinoma invasive potential. Hyaluronidase may play an integral role in breast cancer invasion and metastasis.

Adenocarcinoma↗
PubMedDate not supplied

[Identification of a novel human MAST4 gene, a new member of the microtubule associated serine-threonine kinase family].

Human protein kinases make up a large superfamily of homologous proteins, which are related by virtue of their kinase domains (also known as catalytic domains). Here we report the cloning and characterization of a novel human MAST4 (microtubule associated serine/threonine kinase family member 4) gene, which locates on human chromosome 5q13. The MAST4 cDNA is 7587 base pairs in length and encodes a putative protein of 2435 amino acids which contains a serine/threonine kinase domain and a PDZ domain. MAST4 protein has 64%, 63%, 59% and 39% identical aminoacid residues with MAST1, MAST2, MAST3 and MASTL respectively. RT-PCR analysis revealed relatively high expression level of MAST4 in most normal human tissues, with an exception of in testis, small intestine, colon and peripheral blood leukocyte.

Amino Acid Sequence↗