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Biomedical subjects

R Ng

Publications and source records attributed to R Ng.

At least 37 records · Page 2Linked to original sources

Structural studies on centromeres in the yeast Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, circular or linear plasmids containing a functional centromere (CEN) and a chromosomal replicator (ARS) are mitotically stable and segregate as ordinary yeast chromosomes in the first and second meiotic divisions. A centromere in S. cerevisiae consists of a region of DNA, approximately 150 bp in length, containing three important sequence elements, which are folded with proteins into a specific conformation in the chromatin (the yeast kinetochore). Each of the functional CEN sequences contains a high (91% to 95%) AT region (element II), 78 to 86 bp in length, flanked on one side by the common sequence PuTCACPuTG (element I), and on the other by the sequence TGTTT.TG.TTTCCGAAA....AAA (element III). Deletions in the element II region partially inactivate mitotic function and cause precocious separation of the sister chromatids in meiosis I. Element III appears to be a protein binding site, as evidenced by the following observations. Various point mutations in element III inactivate centromere function, especially in the central CCG (17). One or more protein binding sites in the element III region can be demonstrated by an exonuclease III blocking assay. Wild-type CEN sequences compete strongly in this binding assay, whereas certain functionally inactive mutant CEN sequences do not. In addition, various DNA segments containing either CEN3 or the element III region strongly repress expression of the yeast GAL1 gene when inserted immediately upstream from the transcriptional start site. Helical DNA segments containing CEN3 or CEN14 are shown to be bent or distorted in shape in the high-AT element II region.

Base Sequence↗

Canine orthotopic liver transplantation--is systemic veno-venous shunting necessary?

The experience of a single operating team performing the first 30 consecutive orthotopic liver transplants in dogs is reported. In 22 experiments during the anhepatic phase and as the liver graft is inserted in the recipient animal, the portal circulation is protected by a shunt to the jugular vein. Nine dogs survived 2-17 days. In 8 other unselected animals, both the portal vein and the infrahepatic vena cava were shunted to the jugular vein. Although blood pressure was better maintained in animals with 2 shunts, only one dog survived 10 days. Mention is also made of 11 subsequent transplant operations using a single porta-jugular shunt but reducing operating time by having 2 surgeons working on the donor and recipient animal simultaneously. Nine of the 11 dogs survived 2-6 days after the liver transplantation. The survival figures are comparable to those of other centres where double shunting is routinely performed. Our experience suggests that systemic veno-venous shunt may be omitted if the transplant procedure is performed expeditiously.

Animals↗

Effect of sample dilutions on arterial blood gas determinations.

A study was undertaken to determine the blood gas effects of incompletely purging heparinized saline flush solution from an indwelling arterial catheter and pressure tubing. Hematocrit and blood gases were measured after withdrawing 0, 2, 4, 6, 8, and 10 ml of flush-blood solutions before sampling from a 20-ga radial artery catheter and 7-ft pressure tubing and stopcock. The pH and hematocrit were nearly unchanged between purging volumes of 8 and 10 ml. The PaO2 had a 2.4% error, while the PaCO2 had a 4.4% error. Because there is no standard arterial line setup, it is recommended that each ICU undertake a similar study to determine the optimal volume of aspirated flush-blood solution before blood gas sampling, in order to achieve accurate blood gas results and minimize blood waste.

Blood Gas Analysis↗

Plasminogen activator activity in human breast cancer cytosols.

Plasminogen activators are an enzyme complex which first appears in the trophoblast and may contribute to the invasive and metastatic process in neoplastic growth. In this study, 102 cytosols from human breast cancer biopsies were analyzed for PAA (with the chromogenic tripeptide S2251 KABI), steroid receptors (ER and PR), age, nodal and menopausal status. The data were submitted to log (X + 1) transformation and the raw and transformed data were analyzed for distribution. Because of the largely non-normal distribution of the data, Spearman's rank order correlation coefficients were generated to test for relationships between these differentiation markers and the clinical data. Nodal and menstrual status groups were compared for PAA and receptor levels using the Wilcoxon rank sum test. We found significant positive correlations between net PAA and ER (p = 0.0001), net PAA and PR (p = 0.0001), and net PAA and age (p less than 0.05). PAA levels for nodal status groups were found to be significantly different (negative at p less than 0.05). Nodal metastases predict poor prognosis while higher receptor levels indicate a better prognosis. As PAA levels correlate with the above biologic properties of breast tumors, they may provide additional prognostic information, especially in cases in whom auxiliary node status is unknown.

Breast Neoplasms↗

Chemical and clinical evaluation of the random access analyzer "RA-1000".

In the RA-1000, a random-access discrete analyzer, an inert fluorocarbon fluid is used to prevent interaction and carryover. Production-model instruments were evaluated in two laboratories with respect to determination of glucose, creatinine, total protein, inorganic phosphorus, cholesterol, alkaline phosphatase, lactate dehydrogenase, creatine kinase, gamma-glutamyltransferase, and aspartate and alanine aminotransferases. Within-run, among-run, and day-to-day (for 15 days) precision was assessed, and results were correlated with those obtained by the methods routinely in use in our departments. Precision was excellent, correlation acceptable.

Autoanalysis↗

Plasminogen activators as markers of tumor colonization potential.

Cell suspensions from the R 3230 AC rat mammary adenocarcinoma, when injected intravenously into F344 rats, invariably produce multiple lung foci within 10 days. We compared the colonization potential of cultures obtained from these foci and from cell populations exposed to 100 micrograms/ml medium of both concanavalin A and wheat germ agglutinin for 5 passages with the original cell line. Plasminogen activator activity (PAA) was determined in all three cell subpopulations, using S2251 (KABI) as chromogenic substrate. All cell lines retained their ability to grow after subcutaneous implant. The lectin resistant variant was found to have lost its capacity to nidate in the lung completely and also had the lowest PAA. In contrast, the cell population derived from the lung foci ranked highest in PAA.

Adenocarcinoma↗

Isolation and sequence of the gene for actin in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae is known to contain the highly conserved and unbiquitous protein actin. We have used cloned actin sequences from Dictyostelium discoideum to identify and clone the actin gene in yeast. Hybridization to genomic fragments of yeast DNA suggest that there is a single actin gene in yeast. We have determined the nucleotide sequence of that gene and its flanking regions. The sequence of the gene reveals an intervening sequence of 309 base pairs in the coding sequences at the 5' end of the gene. The existence and location of the intervening sequence was verified by using the dideoxy chain termination technique to determine the sequence at the 5' terminus of the actin mRNA. The similarity of the splice junction sequences in this gene to those found in higher eukaryotes suggests that yeast must possess a similar splicing enzyme.

Actins↗

Ebstein's anomaly: late results of surgical correction.

Between 1969 and 1976, 10 severely disabled patients with Ebstein's anomaly were operated on at the National Heart Hospital using replacement of the tricuspid valve with mounted aortic homografts [9] or dura mater valve [1], plication of the atrialized right ventricle [10], and closure of an associated interatrail communication. 7 survivors have been followed up from 2 to 9 yr. 5 are asymptomatic. Symptomatic tricuspid regurgitation developed in 2 patients; from a paravalvar leak of the tricuspid homograft in one, and in the other calcification with stenosis in an irradiated homograft, 2.5 and 7.5 yr later. Permanent pacemakers were needed in 2 patients, 3 wk and 18 mth after surgery for symptomatic heart block. Despite corrective surgery for the structural abnormalities in Ebstein, late results remain influenced by disorders of rhythm and conduction disturbances, degenerative changes in the valves used for replacement and the intrinsic primary myocardial disease. Such "corrective" procedures in patients with Ebstein's anomaly can result in maintained symptomatic improvement but must be regarded as palliative surgery.

Adolescent↗

Lead poisoning from lead-soldered electric kettles.

Lead poisoning occurred in two infants, causing lead encephalopathy in one but no symptoms in the other. Both infants had been fed a formula prepared with water boiled in a lead-soldered electric kettle. The diagnosis was suggested by dense metaphyseal bands in radiographs, illustrating the importance of careful examination of "routine" radiographs, particularly in asymptomatic infants.

Bone and Bones↗

Chemotherapy of an experimental glioma with nitrosoureas.

Chemotherapy experiments were performed with 2 nitro-sourea drugs in an experimental mouse brain tumor model. Cell suspensions of a transplantable mouse ependymoblastoma were injected i.c. by means of a stereotactic frame. The drugs used were 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea and were given by either i.p. or by direct intraneoplastic (i.n.) injection on the fifth day after tumor cell implantation. Injections i.n. of drugs were made with the stereotactic frame. Both drugs were highly effective in increasing the median day of death and in yielding large numbers of long-term survivors. Effectiveness was evident after i.p. or i.n. injection. However, with certain dosage schedules such as every 2 hr for 5 injections daily on 2 consecutive days, i.n. injection was more effective and less toxic than i.p. injection. The reason why repeated i.n. injections produced less toxicity than repeated i.p. injections is not definitely known but may be due to local metabolism of the drugs in the tumors and surrounding brain to a less toxic form. This is the first laboratory report of direct i.n. injection of the nitrosoureas, and the authors consider these results encouraging.

Animals↗

Alteration of polynucleotide secondary structure by ribosomal protein S1.

Ribosomal 30S protein S1 causes disruption of the secondary structure of certain pyrimidine-containing polynucleotides. Helical poly(U), poly(C, U), and neutral and acidic poly(C) are stoichiometrically converted by S1 to structures indistinguishable from their partially or completely thermally denatured forms, as revealed by circular dichroism. Of the several double- and triple-stranded helical polynucleotides tested that contain one polypurine strand and at least one polypyrimidine strand, only the conformation of the DNA.RNA hybrid, poly(A)-poly(dT), is perturbed. In the presence of S1, this hybrid undergoes a transition to a new structure that has a circular dichroism spectrum unlike either the native or thermally denatured forms. Intercalated ethidium bromide is released from poly(A)-poly(dT) by S1, confirming the occurrence of a conformational rearrangement. The translation inhibitor, autintricarboxylic acid, completely inhibits the action of S1 on polypyrimidines, but has no effect on the conformational perturbation of poly(A(-poly(dT). The possible relation between these observations and the biological function of protein S1 is discussed.

Circular Dichroism↗

Ebstein's anomaly. Genetic study of 26 families.

The families of 26 patients with Ebstein's anomaly were examined. There were 120 first-degree relatives, 100 of whom were living, and 93 of these were examined. Information was available on 14 of the 20 who had died. No case of Ebstein's anomaly was found among the first-degree relatives, but 2 had ventricular septal defects and another, who died at 7 months, was said to have had congenital heart disease. In more distant relatives there were 6 with congenital heart disease, including 2 with ventricular septal defects and 2 with Fallot's tetralogy.

Ebstein Anomaly↗