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Biomedical subjects

N Lee

Publications and source records attributed to N Lee.

At least 289 records · Page 16Linked to original sources

The cutaneous R-pulse interval: its application as a clinical measure of neonatal cardiovascular function.

The time interval from the onset of the R wave of the ECG to the onset of the cutaneous capillary pulse wave, i.e., cutaneous R-pulse interval or RPIc, was evaluated in 21 full-term and 22 preterm infants as a measure of cardiovascular function. RPIc showed a significant linear relationship with birth weight (r = .58, p less than .001) and gestational age (r = .62, p less than .001) for healthy infants. At similar gestational ages, the sick infants showed a significant prolongation of RPIc when compared to their healthy counterparts (mean prolongation 18.5 msec, p less than .01). The infusion of calcium gluconate, an inotropic agent, consistently and significantly shortened the RPIc from its preinfusion value (p less than .01). In 7 infants, simultaneous measurement of intra-aortic R-pulse interval accompanied parallel changes in RPIc. These preliminary observations suggest that continuous monitoring of RPIc may provide a reliable noninvasive measure of neonatal cardiovascular function.

Calcium Gluconate↗

Do cooking fuels pose a risk for lung cancer? A case-control study of women in Hong Kong.

Two hundred female lung cancer patients and 200 female district controls in Hong Kong were interviewed about their previous use of various types of cooking fuels to assess whether any association could be found with lung cancer risk. Mixed results were found when the data were analyzed in terms of ever-exposed vs never-exposed duration, and relationship with smoking. Cases were found to have slightly more exposure to kerosene, whereas controls were likely to have used the cleaner, but more expensive, liquid petroleum gas (LPG) type of fuel. Because the evidence was conflicting if evaluated in terms of consistency, strength, specificity, and coherence of the associations, it was concluded that the small differences in exposure levels between the cases and controls probably reflected their socio-economic circumstances rather than risk for lung cancer. No interaction effect was found between kerosene exposure and smoking.

Cooking↗

Therapeutic selectivity of and predication of response to 2'-deoxycoformycin in acute leukaemia.

Seventeen patients with acute leukaemia refractory to conventional chemotherapeutic agents were treated with the adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF). Of the twelve patients with acute lymphoblastic leukaemia of the thymic phenotype (Thy-ALL), seven went into complete remission after one or two courses of therapy. Two other (Thy-ALL) patients showed good partial response, and three were resistant to dCF. The five patients with acute leukaemia of other phenotypes had progression of disease despite treatment with dCF. Response to dCF can be predicted from the pattern of change in cellular nucleotide levels in blood and/or bone marrow blasts which have been treated in vitro with dCF and deoxyadenosine. The main adverse effects of dCF therapy were renal and liver dysfunction, conjunctivitis, and haemolysis.

Acute Disease↗

DNA synthesis in thymic-acute lymphoblastic leukaemia.

Deoxyribonucleoside triphosphate (dNTP) concentrations were measured in bone marrow and peripheral blood leucocytes from seven patients with acute Thy-lymphoblastic leukaemia (Thy-ALL), 12 patients with acute myeloblastic leukaemia and 15 patients with acute non-T, non-B lymphoblastic leukaemia (c-ALL), and in thymocytes from patients with myasthenia gravis. Labelled thymidine and deoxycytidine incorporation into DNA was also studied. In Thy-ALL, dNTP concentrations were markedly increased compared with those in the other acute leukaemias. The dNTP concentrations in thymocytes were, however, similar to those in Thy-ALL. 3H-nucleoside incorporation studies showed a marked difference in labelled deoxycytidine incorporation and particularly in the deoxycytidine/thymidine DNA labelling ratio between Thy-ALL and the other cell types. We conclude that the pathways of DNA synthesis in Thy-ALL blasts are different from those in the cells from acute acute leukaemias and some but not all these differences may correspond to differences between normal cortical thymocytes and bone marrow cells.

Bone Marrow↗

Studies on the biochemical sequelae of therapy in Thy-acute lymphoblastic leukaemia with the adenosine deaminase inhibitor 2' deoxycoformycin.

In four patients with Thy-acute lymphoblastic leukaemia changes in blast cell deoxynucleoside triphosphate concentrations and, in three, changes in blast cell S-adenosyl homocysteine hydrolase activity were measured during treatment with 2' deoxycoformycin, a potent inhibitor of adenosine deaminase. These studies were aimed at identifying the molecular basis of cell killing by this drug. In three patients an increase in blast deoxyadenosine triphosphate (dATP) concentration occurred which was found to be temporally related to cell killing and was accompanied by decreased concentrations of the other three deoxyribonucleoside triphosphates. In the one patient with Thy-ALL who responded poorly to treatment, the increase in dATP concentration was delayed and was not accompanied by a fall in the concentrations of the other deoxyribonucleoside triphosphates. Progressive inactivation of blast cell S-adenosyl homocysteine hydrolase was found to occur in the three patients tested but was maximal only after a substantial reduction of peripheral blast cell count. These results show that 2' deoxycoformycin has a potent cytoreductive effect in Thy-ALL and suggest that the molecular basis of this toxicity is related both to the intracellular accumulation of dATP with inhibition of ribonucleotide reductase. Inactivation of S-adenosyl homocysteine hydrolase may be of importance as an additional mechanism.

Adenosine Deaminase↗

Expression of the Serratia marcescens lipoproteins gene in Escherichia coli.

The lipoprotein gene (lpp) of Serratia marcescens was cloned in a lambda phage vector (K. Nakamura and M. Inouye, Proc. Natl. Acad. Sci. U.S.A. 77: 1369-1373, 1980). This lpp gene was recloned in plasmid vectors pBR322 and pSC101. When a lipoprotein-deficient (lpp) mutant of Escherichia coli was transformed with pBR322 carrying the S. marcescens lpp gene, cells became nonleaky for ribonuclease, resistant to ethylenediaminetetraacetic acid, and sensitive to globomycin. The lipoprotein was found exclusively in the outer membrane fraction. These results indicate that the S. marcescens lipoprotein was normally secreted across the cytoplasmic membrane, modified, and assembled in the E. coli outer membrane. The amount of the free-form lipoprotein produced in this system was three times higher than that produced in lpp + C. coli cells, whereas there was no difference in the amount of the bound-form lipoprotein. On the other hand, lpp E. coli cells which harbored pSC101 carrying the S. marcescens lpp gene produced only one-third of the free-form lipoprotein produced in lpp E. coli cells which harbored pSC101 carrying the E. coli lpp gene. One of the major factors causing this difference in efficiency of gene expression between the lpp genes of S. marcescens and E. coli appears to be a deletion mutation at the transcription termination region found in the cloned S. marcescens lpp gene. The functional half-life of the S. marcescens lpp messenger ribonucleic acid in E. coli was found to be found half that of the E. coli lpp messenger ribonucleic acid.

Cell Membrane↗

Persistence of chlamydial infection after treatment for neonatal conjunctivitis.

A high incidence of pharyngeal infection was found in babies with isolation-positive chlamydial conjunctivitis. Chlamydia trachomatis was isolated from the pharynx of 12 (52%) of 23 babies before treatment, and was reisolated from the eyes of 4 (12%) of 34 and from the pharynx of 14 (41%) of 34 after treatment. C trachomatis was reisolated significantly more often from babies treated only with topical tetracycline for 4 weeks (75%) than from those treated with both topical tetracycline and oral erythromycin for 2 weeks (32%). Reisolation from the eyes was associated with only minor clinical signs. Radiological signs of an inflammatory lesion in the chest were found in 2 of 8 babies examined because of persistent cough. These signs were not associated with high or rising titres of serum chlamydial antibody.

Chlamydia Infections↗

The araC gene of Escherichia coli: transcriptional and translational start-points and complete nucleotide sequence.

The nucleotide sequence of the Escherichia coli araC gene and flanking regions have been determined from a series of overlapping fragments using the technique of base-specific chemical cleavage of Maxam and Gilbert (1980). The nucleotide sequence of araC gene was confirmed by the partial amino acid sequences of araC protein and its methionine peptides. The primary structure of araC polypeptide consists of 291 amino acid residues, giving it a chemical molecular weight of 33 314 daltons. The transcriptional start-point has been deduced from the sequence of araC mRNA synthesized in vitro and in vivo, and it is located 148 bp away from the transcriptional start-point of the araBAD operon. The translational start-point for the araC gene was deduced from the N-terminal amino acid sequence of the protein, and is located 165 bp from the 5'-end of araC mRNA. There is, therefore, a leader sequence of 164 bp preceding the araC gene.

Arabinose↗

Inhibition of thromboxane synthesis and platelet aggregation by pyridine and its derivatives.

Pyridine inhibited the conversion of PG endoperoxide to TXA2 catalyzed by TX synthetase from human platelet and swine lung microsomes. The inhibitory potency of pyridine is abolished by derivatizing pyridine at the 2-position but is increased by introducing hydrophobic substituents at 3- or 4-positions, with 3-substituted pyridines being the most potent inhibitors. Inhibition by pyridine and its derivatives was also selective, since other enzymes in the arachidonic acid cascade were not significantly affected. Pyridine and the active derivatives also inhibited human platelet aggregation induced by arachidonic acid or ADP.

Animals↗

Visual loss caused by corneal crystals in myeloma: rapid improvement and plasma exchange and chemotherapy.

Recognition of needle-like crystals in the cornea of a patient with deteriorating visual acuity initiated laboratory studies which demonstrated underlying multiple myeloma. Crystal deposition in the cornea occurs only rarely in multiple myeloma, and evidently reflects an unusual tendency for certain paraproteins to form numerous small aggregates which are deposited particularly within, and between, corneal epithelial cells. Treatment with chemotherapy, plus repeated plasma exchange with a normal plasma protein product resulted in significant depletion of crystals, and improvement in visual acuity over a period of three weeks. Accelerated clearance of paraprotein by plasmapheresis appeared to contribute materially to the rapidity of recovery, since recovery was considerably faster than in reported cases where treatment was with chemotherapy alone.

Aged↗

Cholesterol levels and plasma membrane fluidity in 3T3 and SV101-3T3 cells.

Polyene antibiotics such as filipin selectively inhibit wheat germ agglutinin-induced agglutination of transformed and malignant cells compared to normal cells (Hatten ME, Burger MM: Biochemistry 18: 739, 1979). Since filipin binds specifically to cholesterol, we measured cholesterol levels in 3T3 cells and SV101-3T3 cells. SV101-3T3 cells contained 50-100% more cholesterol per cell than 3T3 cells. Both cell types were starved for cholesterol by growth in lipid-depleted medium plus 25-hydroxycholesterol. The cholesterol level of SV101-3T3 cells decreased by 30-50%, while the level in 3T3 cells remained constant. Filipin-stained SV101-3T3 cells revealed bright patches of filipin under fluorescence microscopy. These patches were absent in 3T3 cells and in SV101-3T3 and 3T3 cells starved for cholesterol. We selectively labeled plasma membranes of these cells with a spin label analog of phosphatidylcholine. The spin label indicated differences in plasma membrane fluidity that may be related to the different cholesterol levels in 3T3 and SV101-3T3 cells.

Animals↗