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Biomedical subjects

W H Walker

Publications and source records attributed to W H Walker.

At least 37 records · Page 2Linked to original sources

NF-kappa B: a family of inducible and differentially expressed enhancer-binding proteins in human T cells.

A sensitive DNA-protein crosslinking approach has been used to characterize four inducible T-cell proteins (50 kDa, 55 kDa, 75 kDa, and 85 kDa) that specifically bind to kappa B enhancer elements. Partial proteolytic mapping revealed a distinct cleavage pattern for three of these proteins. These polypeptides are sequestered as inactive precursors in the cytosol of unstimulated T cells but can be converted into active forms in vivo by phorbol ester stimulation or in vitro by detergent treatment. The induction of these proteins by phorbol ester results in a strikingly biphasic pattern of nuclear expression with the 55-kDa and 75-kDa species appearing within minutes, whereas the 50-kDa and 85-kDa species appear only several hours after cellular stimulation. These data suggest that NF-kappa B-binding activity may not correspond to a single polypeptide but rather a family of at least four inducible and differentially regulated DNA-binding proteins that are expressed with distinct kinetics in human T lymphocytes.

Base Sequence↗

DNA sequences involved in the transcriptional activation of a human placental lactogen gene.

To identify regulatory elements in the promoter of a human placental lactogen gene (hPL3) that are important for its transcriptional activation, sequences 5' to the start of transcription were linked to the reporter gene chloramphenicol acetyltransferase (CAT) and transiently transfected into JEG-3 cells, a human placental choriocarcinoma cell line. In the presence of the hPL3 enhancer, deletion of the promoter sequence between -142 and -129 basepairs resulted in an 8-fold decrease in CAT activity. Similar results were seen with the SV40 enhancer and the hPL3 promoter in HepG2 liver cells. Nuclear proteins from HepG2, HeLa, and JEG-3 cells formed specific binding complexes with this region of the hPL3 promoter by a gel mobility shift assay, indicating that the DNA-binding protein was not tissue specific. The -142 to -129 basepair region contains a sequence similar to that of a variant binding site for the transcription factor Sp1. An oligonucleotide containing Sp1-binding sites specifically competes for proteins binding the hPL3 promoter, and the methylation interference pattern is similar to that for an Sp1-binding site. This suggests that the hPL3 promoter binds Sp1- or an Sp1-like trans-acting factor, and this binding site is important for transcriptional regulation by the hPL3 enhancer in PL-producing cells.

Base Sequence↗

[49 day storage of erythrocyte concentrates in blood bags with the PAGGS-mannitol solution].

The red cell preservation solution PAGGS-Mannitol differs from the well documented PAGGS-Sorbitol only by the exchange from Sorbitol in Mannitol. In a clinical investigation with volunteers, up to 21 of the pure PAGGS-Mannitol solution were infused within 4 h. Blood and urine parameters were determined. The solution was well tolerated, no unexpected change of blood and urine parameters was found. The 24 h red cell in vivo survival rate of PAGGS-Mannitol was found to be 74.5 +/- 4.4%, after 49 days storage, a value which was described for PAGGS-Sorbitol before. In vitro data on storage of red cell concentrates with and without buffy coat were determined for hemolysis, 2,3-DPG and ATP using a blood bag system with DEHP and TOTM plastisized PVC. If 1% hemolysis is regarded as acceptable, red cell concentrates can be stored in PAGGS-Mannitol with a TOTM plastisized blood bag system up to 42 days. Under these conditions the amount of plastisizer in the red cell concentrate was found to be only 1% of the amount determined in a standard DEHP plastisized PVC blood bag system.

Adenine↗

Studies of intestinal permeability in inflammatory diseases using polyethylene glycol 400.

It has been proposed that increased bowel permeability might play a role in the pathogenesis of inflammatory disease. Intestinal permeation was investigated by measuring the 6-hour urinary excretion of polyethylene glycol (PEG) 400 in 40 adult volunteer controls and in patients with inflammatory disease. Of the patients, 15 had Crohn's disease; 7, ulcerative colitis; 2, celiac disease; and 7, rheumatoid arthritis. No significant difference in total urinary excretion over a 6-hour period was found between controls and patients with ulcerative colitis. Patients with Crohn's disease, celiac disease, or with rheumatoid arthritis were found to have significantly decreased urinary excretion of PEG 400. The results of this study indicate that there is no identifiable increase in intestinal permeation as measured by PEG 400 excretion during periods of active inflammatory disease.

Adult↗

Studies of thyroxine binding to plasma proteins in health and disease.

Thyroxine binding protein characteristics were defined in 6 normal subjects, 4 with thyroxine binding globulin (TBG) deficiency, 3 with TBG increase, one with hyperthyroxinemic dysalbuminemia, 7 with severe non-thyroidal illness, and 3 with chronic renal failure. Free thyroxine was measured by Sephadex partition in plasma to which increasing thyroxine concentrations were added. Deconvolution of the resultant titration data was performed by computer modelling. Abnormalities of thyroxine binding capacities or of binding affinities occur in non-thyroidal illness, chronic renal failure, and sporadically. The patient with hyperthyroxinemic dysalbuminemia had increased thyroxine binding affinity to thyroxine binding prealbumin as well as to albumin. "Free-T4 assays" or estimates of Free-T4 by calculation from total thyroxine and measures of protein binding such as T3-uptake must be expected to be perturbed by these binding protein abnormalities unless such interferences are explicitly demonstrated to be absent.

Adult↗

Role of serum androgens and sex hormone binding globulin capacity in the evaluation of hirsutism in women.

Serum samples from 23 hirsute women and 23 non-hirsute women matched for age and deviation from ideal weight were analyzed for total testosterone (T), percent free testosterone (% FT) and sex hormone binding globulin capacity (SHBG). The % FT was assayed by 2 methods, using diluted serum in equilibrium dialysis (EQD) and using undiluted serum in centrifugal ultra-filtration (UF). SHBG was measured by a DEAE cellulose filter assay and T by radioimmunoassay. The two methods for determining % FT correlated well. There was considerable overlap between the hirsute and control groups for all of the measured parameters. The discrimination between the 2 groups provided by the indirect estimate of free testosterone obtained from the ratio of T to SHBG was at least as good as that provided by the free testosterone derived from ultrafiltration or dialysis.

Adult↗

Human embryonic zeta-globin chains in adult patients with alpha-thalassemias.

Human embryonic zeta-globin chains are alpha-globin-like chains that are normally present during the first three months of gestation. In this investigation, zeta-globin chains measured by a specific and sensitive radioimmunoassay and by an electrophoretic technique were found to be present in all 7 patients studied with hereditary Hb H disease, and in 8 out of 24 patients with alpha-thalassemia trait. zeta-Globin chains were not detected in 20 other patients with beta-thalassemia trait. These results suggest that the deletion of two alpha-globin genes on the same chromosome is accompanied by the continued expression of embryonic zeta-globin genes in adult individuals.

Adolescent↗

Variations in urinary levels of free 6 beta-hydroxycortisol, cortisol, and estrogens in late pregnancy.

The urinary excretion of 6 beta-hydroxycortisol (6 beta-OHF), free cortisol, and estriol was studied at 4-hourly intervals in 9 subjects between the 36th and 38th week of pregnancy. The ratio of 6 beta-OHF to creatinine showed a significant diurnal rhythm with a 40% fall from a peak at 06.00-10.00 h to a trough at 22.00-02.00 h. There was a significant positive correlation between the excretion of 6 beta-OHF and free cortisol. Estrogen excretion showed no diurnal variation. No increase was observed in the 6 beta-OHF:creatinine ratio in early morning urine samples from 5 subjects followed daily prior to the onset of spontaneous labour at term. Normal nonpregnant females were also found to excrete significant quantities of 6 beta-OHF. These findings suggest that the clinical significance of 6 beta-OHF levels measured in a single void sample of urine has to be reassessed in the face of such a marked diurnal variation.

Circadian Rhythm↗

Usefulness of serial determinations of myoglobin and creatine kinase in serum compared for assessment of acute myocardial infarction.

Twenty-one patients with their first myocardial infarction underwent serial blood sampling every 2 h for determination of serum creatine kinase (CK) and myoglobin during the first 48-72 h after onset of pain. The first blood sample, obtained at a mean time of 4.4 h after infarct onset, invariably showed increased myoglobin (mean, 8.3-fold normal), whereas CK was often normal (mean, 1.6-fold normal). Peak myoglobin values occurred earlier than peak CK values (9.9 h vs 21.6 h, p less than 0.0005), but there was a significant correlation of peak values (myoglobin = 0.384CK - 0.264, r = 0.794, p less than 0.0005). The mean exponential disappearance rate (Kd) of CK was 0.00106 min-1 and of myoglobin was 0.00265 min-1 (p less than 0.0005). The disappearance of myoglobin was well described by a mono-exponential expression except in two patients. The total duration of the increase in myoglobin was significantly less than that of CK (34.7 h vs 74.4 h, p less than 0.0005).

Creatine Kinase↗