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Biomedical subjects

M White

Publications and source records attributed to M White.

At least 325 records · Page 18Linked to original sources

Monocyte membrane ferritin in hemochromatosis.

To further evaluate a possible abnormality in the reticuloendothelial cells in hemochromatosis, the binding of a monoclonal anti-human liver ferritin antibody to monocytes was studied in 19 patients with hemochromatosis, 8 patients with secondary iron overload, 1 patient with hyperferritinemia without iron overload, and 15 normal volunteers. Binding of the antibody to the monocytes was analyzed using a fluorescence-activated cell sorter (FACS). Binding of the anti-ferritin antibody to monocytes was demonstrated in 34.7 +/- 4.5% (mean +/- standard error) of the monocytes in untreated hemochromatosis patients (mean serum ferritin = 2294 +/- 415 micrograms/L), 6.75 +/- 2.03% in treated hemochromatosis patients (mean serum ferritin = 263 +/- 85 micrograms/L), 12.3 +/- 2.7% of the monocytes in the secondary iron overload patients (mean serum ferritin = 2476 +/- 867 micrograms/L), 4.1% in the patient with hyperferritinemia (serum ferritin = 1192) and 4.1 +/- 0.5% of the monocytes in the normal volunteers (mean serum ferritin = 55.2 +/- 11.9 micrograms/L). % binding of anti-ferritin antibody was significantly greater in hemochromatosis patients compared to patients with secondary iron overload (p less than 0.05) despite a comparable degree of iron overload in the secondary iron overload group. The addition of exogenous human ferritin to samples from treated hemochromatosis patients and normal volunteers did not significantly increase the % of monocytes binding anti-ferritin antibody. These results suggest that monocytes from iron-loaded hemochromatosis patients express increased surface ferritin which may represent release of ferritin and a metabolic defect characteristic of hemochromatosis.

Antibodies, Monoclonal↗

Direct relationship between remission duration in acute myeloid leukemia and cell cycle kinetics: a leukemia intergroup study.

Cell cycle characteristics including labeling indices (LI), duration of S-phase (Ts), and total cell cycle time (Tc) were determined in 54 standard-risk, newly diagnosed patients with acute myeloid leukemia following an infusion of bromodeoxyuridine. Remission induction therapy consisting of cytosine arabinoside and daunomycin was then administered to all patients, followed by three courses of consolidation to those who achieved complete remissions (CR). Older patients appeared to have more rapidly cycling cells (P = .003). No unique cell cycle characteristics were identified for patients who achieved remission versus those who had resistant disease. However, the pretherapy cell cycle characteristics were a strong prognosticator for remission duration. CR patients were divided into those whose leukemic cell Tc were above median (A) and below median (B). Among 14 B patients, median duration of response was 211 days, and all relapsed by day 600. Among 18 A patients, the median has not as yet been reached, with nine patients in continuous complete remission (log rank P = .007, Wilcoxon P = .04). We conclude that cell cycle characteristics of leukemic cells play a role in determining remission duration, perhaps because the leukemic cells of the former patients regrow slowly between courses of chemotherapy.

Bone Marrow↗

Stimulation via CD3-Ti but not CD2 induces rapid tyrosine phosphorylation of a 68-kDa protein in the human Jurkat T cell line.

Tyrosine phosphorylation is an early biochemical event associated with surface receptor triggering in many cellular systems. In T lymphocytes, Ag receptor (CD3-Ti) stimulation results in tyrosine phosphorylation of the CD3 zeta subunit. The tyrosine kinase responsible for this modification after CD3-Ti triggering has not been identified. Here we reported that a 68-kDa T cell membrane-associated protein (pp68) in human Jurkat T cells is phosphorylated on tyrosine residues within 1 min after anti-CD3 mAb addition. This induced tyrosine phosphorylation is detected either by in vivo [32P]orthophosphate labeling of the Jurkat T cells or by in vitro [32P]ATP labeling after immunoprecipitation by antiphosphotyrosine antibody. In contrast, mAb stimulation via CD2 and CD4 structures does not induce phosphorylation of pp68. These data are among the first to provide evidence that CD3-Ti and CD2 activation pathways are distinct. Furthermore, they imply that pp68 is itself a tyrosine kinase and/or is a rapidly phosphorylated substrate of a tyrosine kinase.

Antigens, Differentiation, T-Lymphocyte↗

Envelope gene sequence of HTLV-1 isolate MT-2 and its comparison with other HTLV-1 isolates.

The DNA sequence of the envelope gene of the HTLV-1 proviral clone MT-2 was determined and compared with envelope sequences of other HTLV-1 isolates. The comparison of this sequence with another of Japanese origin and two of Caribbean origin does not support the proposal by K.T.A. Malik, J. Even, and A. Karpas (J. Gen. Virol. 69, 1695-1710, 1988) that isolates of similar geographic origins are more homologous than isolates of different origins. No significant differences in the degree of homology could be found among the HTLV-1 envelope gene sequences from Japanese and Caribbean isolates. The comparison confirms the high degree of homology previously found between various HTLV-1 isolates (greater than 97%).

Amino Acid Sequence↗

Stroke volume measurements by electrical bioimpedance and echocardiography in healthy volunteers.

To evaluate the validity of three equations for estimation of thoracic electrical field size in a new bioimpedance algorithm, stroke volume (SV) as calculated by these equations was compared with that calculated by Doppler echocardiography in 48 healthy volunteers, both lean and obese. When the volume of electrically participating tissue was estimated from body height (modified Sramek) or body height corrected for body habitus (Sramek-Bernstein), there was considerable variation between bioimpedance and Doppler stroke volumes. When the volume of electrically participating tissue was estimated from the actual measurement of the height of the thorax and the circumference at the base of the thorax, the variation in SV differences decreased substantially (Sramek equation), although still considerable for clinical use, and there was no relationship between SV thus obtained and body habitus. Analysis of calculated stroke indices derived by our Doppler echocardiographic standard, as compared with values in the literature, revealed a systematic underestimation. We conclude that the original Sramek equation systematically underestimates SV by 15% to 20%, and the modified Sramek and Sramek-Bernstein equations systematically underestimates SV by 15% to 20%, and the modified Sramek and Sramek-Bernstein equations systematically overestimate SV in females by about 15%, but provide SV values in males in the predicted range. Further studies on the current assumption that the electrical field size is a truncated cone may improve precision of the bioimpedance method.

Adult↗

Intravenous propofol anaesthesia using a computerised infusion system.

Propofol offers many advantages as a total intravenous anaesthetic agent compared with other agents. However, considerable experience is necessary in order to give an uncomplicated anaesthetic. A mathematical model which describes the pharmacokinetic behaviour of the drug was incorporated into a computerised delivery system which enables the anaesthetist to achieve and maintain a target blood concentration of propofol and to manipulate this at will. The system was used to provide general anaesthesia for 33 healthy patients who underwent general surgery. A strong statistical relationship was found between measured blood propofol concentrations and the corresponding computer predictions (y = -0.50 + 1.36x). No significant differences in this relationship were found between patients who breathed spontaneously (y = -0.71x + 1.43x) and those who received intermittent positive pressure ventilation (y = -0.33 + 1.32x).

Adult↗

Randomized, double-blind trial of 1- versus 4-hour amphotericin B infusion durations.

We conducted a randomized, double-blind trial of 1- versus 4-h infusions of amphotericin B to determine whether there was any difference in infusion-related toxicity. A total of 128 maintenance infusions in 12 patients were studied; 62 were randomized to 1-h infusions (group A) and 66 were randomized to 4-h infusions (group B). We found no significant differences between patients in groups A and B in mean temperature, pulse, or systolic or diastolic blood pressure measured during the infusions. At a significant level of 0.05, the power to detect a mean difference in temperature of 2 degrees C, a pulse difference of 20 beats per min, a decrease in diastolic blood pressure of 10 mm Hg, or a decrease in systolic blood pressure of 20 mm Hg was 0.95. Rigors and chills were noted in 15 of 62 (24.1%) infusions in group A patients and 12 of 66 (18.1%) infusions in group B patients (P = 0.40). Meperidine was required because of severe persistent rigors in 6 of 62 (9.6%) infusions in group A patients and 6 of 66 (8.9%) infusions in group B patients (P = 0.91). An increase in temperature was noted in five (8%) of the group A infusions and seven (10.6%) of the group B infusions (P = 0.63). The mean time to onset of rigors, an increase in temperature, and an increase in pulse occurred significantly earlier in group A than in group B patients (P = 0.02 for all comparisons). We conclude that there is no difference in the incidence or severity of the infusion-related toxicity of amphotericin B with a 1-h infusion rate compared with a 4-h infusion rate. However, the onset of infusion-related toxicity occurs significantly earlier with a 1-h infusion.

Adult↗

The modified Wilson osteotomy for hallux valgus.

The modified Wilson osteotomy for hallux valgus is a double oblique osteotomy through the metatarsal shaft. The distal fragment is displaced laterally and plantarward. The lateral displacement corrects the varus position of the metatarsal, while the plantar displacement prevents the distal fragment from tilting dorsally into a metatarsus elevatus deformity that could produce metatarsalgia. Seventy-four cases of hallux valgus treated by this method were reviewed five years postoperatively. Sixty-six cases (89%) were graded as satisfactory and eight (11%) as unsatisfactory. Roentgenographic analysis in 61 cases showed the operation had reduced the hallux valgus angle by an average of 15 degrees and the intermetatarsal angle by an average of 4 degrees. The operation shortened the first metatarsal by an average of 5 mm. Although this caused callosities on the forefoot, it did not produce metatarsalgia. The operation is technically uncomplicated and yields a high percentage of satisfactory results.

Adolescent↗