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Biomedical subjects

K Lai

Publications and source records attributed to K Lai.

52 records · Page 3Linked to original sources
PubMed1993

Site of bone density measurement may affect therapy decision.

The purpose of this study was to determine whether bone mineral density (BMD) measurements at the lumbar spine and femoral neck provided comparable information to women planning to use that knowledge to help them make a decision about hormone replacement therapy. Eighty-eight healthy Caucasian women, aged 44-59 and within 0 to 5 years of menopause, participated in the study. BMD measurements were performed at the lumbar spine (L1-L4) and the femoral neck by dual energy X-ray absorptiometry (DXA). Criteria suggested by the National Osteoporosis Foundation were used to categorize women as "at risk" for osteoporosis, bone density more than one standard deviation (SD) below the young adult mean, or as "low risk", bone density at or above this level. The results indicated that 46 women would be classified into the low risk category on the basis of spinal BMD alone. However, 28 of these 46 women would fall into the at risk category when the femoral neck BMD was measured. Sixty-one percent of women informed they were at low risk on the basis of spinal BMD would be considered at risk based on femoral neck BMD. When femoral neck BMD was used as the primary risk indicator, 14% of the women classified as low risk would be at risk if spinal BMD were added. These results suggest that both lumbar spine and proximal femur measurements should be made when women are using bone density measurements as an aid in deciding whether or not to use hormone therapy in their postmenopausal years.

Absorptiometry, Photon↗
PubMed1989

31P NMR spectra of ethidium, quinacrine, and daunomycin complexes with poly(adenylic acid).poly(uridylic acid) RNA duplex and calf thymus DNA.

31P NMR provides a convenient monitor of the phosphate ester backbone conformational changes upon binding of the intercalating drugs ethidium, quinacrine, and daunomycin to sonicated poly(A).poly(U) and calf thymus DNA. 31P chemical shifts can also be used to assess differences in the duplex unwinding angles in the presence of the drug. Thus a new 31P signal, 1.8-2.2 ppm downfield from the double-stranded helix signals, is observed in the ethidium ion-poly(A).poly(U) complex. This signal arises from phosphates which are in perturbed environments due to intercalation of the drug. This is in keeping with the hypothesis that the P-O ester torsional angle in phosphates linking the intercalated base pairs is more trans-like. Similar though smaller deshielding of the 31P signals is observed in sonicated poly(A).poly(U)-quinacrine complexes as well as in the daunomycin complexes. The effect of added ethidium ion, quinacrine, and daunomycin on the 31P spectra of sonicated calf thymus DNA is consistent with Wilson and Jones' (1982) earlier study. In these drug-DNA complexes the drug produces a gradual downfield shift in the DNA 31P signal without the appearance of a separate downfield peak. These differences are attributed to differences in the rate of chemical exchange of the drug between free and bound duplex states. The previous correlation of 31P chemical shift with drug duplex unwinding angle (Wilson & Jones, 1982) is confirmed for both the RNA and DNA duplexes.

DNA↗
PubMed1988

Subacute myelopathy: an unusual paraneoplastic complication of Hodgkin's disease.

We report a case of Hodgkin disease presenting with a subacute myelopathy without evidence of metastatic involvement of the spinal cord. The systemic disease responded to conventional chemotherapy, but the myelopathy only improved after intrathecal dexamethasone was added to the treatment program, beta-2-microglobulin levels in the cerebrospinal fluid were elevated at presentation. Following the use of intrathecal corticosteroids there was a decrease of CSF beta-2-microglobulin levels. The possible significance of these findings is discussed.

Acute Disease↗
PubMed1985

Spatial distribution and size of acetylcholine receptor clusters determined by motor nerves in developing chick muscles.

The size and distribution of acetylcholine receptor clusters (AChR-C) on normal and aneural developing muscle fibres of the chick wing were studied by labelling AChR with fluorescent conjugates of alpha-bungarotoxin (alpha-BGT). AChR-C of a size typical of initial synaptic contacts (5 micron long) were present at 7 days incubation, shortly after the appearance of nerves, and were grouped in bands corresponding to muscle nerve branches. A regular distribution of large (approximately equal to 5 micron) AChR-C separated by 100-200 micron had developed by 10-14 days in the slow-tonic anterior latissimus dorsi and ulnimetacarpalis dorsalis muscles. The role of motor innervation in the formation of AChR-C was assessed by removing the brachial neural tube at 2 days incubation in order to prevent nerves entering the wing. Neural-tube removal prevented the appearance of the large AChR-C normally associated with the early synaptic contacts. Small AChR-C (less than 2 micron long) appeared in aneural muscles, but these were not grouped into bands characteristic of the large AChR-C in normal muscles. The results suggest that the formation of junctional AChR-C is dependent on nerves.

Animals↗
PubMed1984

31P and two-dimensional 31P/1H correlated NMR spectra of Duplex d(Ap[17O]Gp[18O]Cp[16O]T) and assignment of 31P signals in d(ApGpCpT)2-actinomycin D complex.

A solid-phase phosphoramidite method was used for the synthesis of unlabeled and phosphoryl-labeled d(Ap-[17O]Gp[18O]Cp[16O]T). The ability to label the phosphoryl oxygens of d(ApGpCpT) and thus assign the 31P signals, combined with a two-dimensional 31P/1H chemical shift correlated NMR spectral technique, provided a novel means for the ready assignment of the H5' and H3' protons coupled to the phosphates. Phosphoryl labeling has also allowed us to assign the 31P NMR signals in the actinomycin D-d(Ap-[17O]Gp[18O]Cp[16O]T)2 duplex complex and confirm that the drug intercalates between the GpC stacked base pairs.

Binding Sites↗
PubMed1982

Phosphorus-31 nuclear magnetic resonance of double- and triple-helical nucleic acids. Phosphorus-31 chemical shifts as a probe of phosphorus-oxygen ester bond torsional angles.

The temperature dependence to the 31P NMR spectra of poly[d(GC)] . poly [d(GC)],d(GC)4, phenylalanine tRNA (yeast) and mixtures of poly(A) + oligo(U) is presented. The 31P NMR spectra of mixtures of complementary RNA and of the poly d(GC) self-complementary DNA provide torsional information on the phosphate ester conformation in the double, triple, and "Z" helix. The increasing downfield shift with temperature of the single-strand nucleic acids provides a measure of the change in the phosphate ester conformation in the single helix to coil conversion. A separate upfield peak (20-60% of the total phosphates) is observed at lower temperatures in the oligo(U) . poly(A) mixtures which is assigned to the double helix/triple helix. Proton NMR and UV spectra confirm the presence of the multistrand forms. The 31P chemical shift for the double helix/triple helix is 0.2-0.5 ppm upfield from the chemical shift for the single helix which in turn is 1.0 ppm upfield from the chemical shift for the random coil conformation.

Magnetic Resonance Spectroscopy↗
PubMedDate not supplied

Structure-function analyses of a common mutation in blacks with transferase-deficiency galactosemia.

We previously identified a missense mutation at amino acid 135 of human galactose 1-phosphate uridyltransferase (hGALT) in which a leucine (TTG) was substituted for a serine (TCG), S135L. This mutation was common in black patients with galactosemia and homozygotes (S135L/S135L) had no GALT activity or protein in their erythrocytes or lymphoblasts. However, there was residual GALT activity and protein in their leukocytes, and they had near normal total body [13C]galactose oxidation to 13CO2 in breath. To evaluate the biochemical mechanism(s) producing these effects, we overexpressed hGALT proteins with site-directed mutations in this nonconserved amino acid in a GALT-minus Escherichia coli. Enzyme activities detected in bacterial lysates overexpressing either S135 (wild type), A135, C135, H135, L135, S132-H135, T135, or Y135 were 100, 4.7, 3.0, 4.0, 2.7, 0.7, 35.4, and 1.4%, respectively. Only the threonine substitution (S135T) had significant enzyme activity in these lysates. There was also decreased abundance of all mutant proteins in the lysates exposed to bacterial proteolysis during preparation and analysis. This added the variable of bio-instability to analysis of enzyme activities in lysates. To further characterize the catalytic role of serine at amino acid 135 and to differentiate bio-instability from impaired catalysis by the leucine substitution, we purified wild-type and L135-hGALT proteins to homogeneity and analyzed identical amounts of enzyme protein. We found that the apparent Vmax of the purified L135-hGALT protein was significantly reduced from 80 +/- 5.9 to 5.8 +/- 1.8 micromol glucose 1-phosphate released/min/mg hGALT protein with no increase in KM for galactose 1-phosphate for the second displacement. The first displacement reaction, although three orders of magnitude slower, was similar between the wild type and L135-hGALT. We conclude that a hydroxyl group on amino acid 135 is required for the catalysis of uridyl transfer from UDP-glucose to UDP-galactose in the presence of galactose 1-phosphate, and plays a role in the bio-stability of hGALT.

Animals↗
PubMedDate not supplied

The molecular biology of galactosemia.

Classic galactosemia is an autosomal recessive disorder caused by the deficiency of galactose 1-phosphate uridyltransferase (GALT). Although the potentially lethal, neonatal hepatotoxic syndrome is prevented by newborn screening and galactose restriction, long-term outcome for older patients with galactosemia remains problematic. After the cloning and sequencing of the GALT gene, more than 130 mutations in the GALT gene have been associated with GALT deficiency; this review relates them to function and clinical outcome. Two common mutations, Q188R and K285N, account for more than 70% of G alleles in the white population and are associated with classic galactosemia and impaired GALT function. In the black population, S135L accounts for 62% of the alleles causing galactosemia and is associated with good outcomes. A large 5 kb deletion in the GALT gene is found in Ashkenazim Jews. The Duarte galactosemia variant is caused by N314D. Homozygosity for N314D reduces GALT activity to 50%. When either E203K or a 1721C-->T transition (Los Angeles variant) are present in cis with N314D, GALT activity reverts to normal. In this review, we discuss the structural biology of these mutations as they affect both the GALT enzyme and patient outcome.

Ethnicity↗
PubMedDate not supplied

Retrospective pharmacoeconomic evaluation of dosing vecuronium by peripheral nerve stimulation versus standard clinical assessment in critically ill patients.

Adjusting the dosage of vecuronium by peripheral nerve stimulation versus standard clinical dosing in critically ill patients reduces drug requirements to maintain a desired depth of paralysis and, on average, produces faster recovery of neuromuscular function. We retrospectively analyzed the health and economic outcomes of using train-of-four (TOF) end points by peripheral nerve stimulation in dosing neuromuscular blocking agents during continuous infusion in a medical intensive care unit (ICU). A decision-analytic model was used to calculate outcomes and costs of treatment using and not using TOF end points of dosing vecuronium. Data from our TOF trial provided the difference in neuromuscular and functional recovery time. Charges billed by the Patient Financial Services Department were used to determine hourly costs of ICU stay for recovery from neuromuscular blockade using costs:charges ratios estimated from a sample of 20 patients. The cost of vecuronium was determined using the hospital acquisition cost and the actual number of milligrams of drug given to each patient in the TOF trial. The cost of performing one TOF event was determined by timing six events performed by six pharmacists, and randomly selecting 60% of these to calculate a mean time/TOF event. The economic impact of dosing by TOF was determined by calculating the cost savings/patient dosed by TOF compared with those who had doses individualized by standard clinical assessment. One-way and multiway sensitivity analyses were performed to assess model uncertainty. The mean drug cost was $286 in the TOF group versus $580 in the standard dosing group. With a mean time/TOF assessment of 5.8 +/- 1.6 minutes, each episode cost $2.92 for a total TOF cost/patient of $23. At $54/hour of recovery time in the ICU, the estimated cost of ICU care for the TOF group was $34,214 versus $118,681 for the standard group. The estimated costs/patient were $459 and $1197, respectively, for a total cost savings/patient of $738. Sensitivity analyses showed the model to be robust. Estimated annual savings of $146,103 are projected by using TOF to individualize vecuronium doses in patients in the ICU. Individualizing vecuronium doses to TOF end points has both therapeutic and economic advantages. When considering costs of drug, TOF monitoring, and ICU, the total cost/patient was 40% of that in the control group.

Costs and Cost Analysis↗