Will we save the children? New York City as child abuser.
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Child Welfare↗
Biomedical subjects
M Phillips
Publications and source records attributed to M Phillips.
In vitro synthesis of IgE by human peripheral blood leucocytes: V. Functional heterogeneity within the IgE-B-cell pool.
Fractionation of human peripheral blood leucocytes (PBL) B cells by differential sedimentation on a discontinuous Percoll gradient separates B cell subpopulations which vary markedly in rates of spontaneous IgE synthesis, often revealing the presence of active IgE secreting cells which are totally suppressed within unfractionated PBL B cell preparations. The production in vitro of IgE by separated B cell populations from the same individual may respond disparately to an identical population of autologous T cells and to pokeweed mitogen. Kinetic studies revealed major differences in both the rates of release of cell-associated IgE between these B cell populations, and their rates of de novo IgE synthesis. From a methodological viewpoint, the use of this B cell fractionation technique is demonstrated to improve greatly the efficiency of detection of T cell-responsive IgE producing B cells in peripheral blood from atopics, and from a mechanistic standpoint raises the possibility that B cell heterogeneity may modulate the functional expression of IgE-regulatory T cells signals.
Adult↗
Sudden cardiac death in Air Force recruits. A 20-year review.
We reviewed the clinical and autopsy records of the 19 sudden cardiac deaths that occurred among the 1,606,167 US Air Force healthy, medically screened recruits (90% male; 17 to 28 years old) during a 42-day basic training period between 1965 and 1985. Sixteen (all male) died suddenly of underlying structural heart disease, whereas no anatomic cause of death was identified in the remaining three. Thirty-two nonsudden, noncardiac deaths occurred during the same period, and only two had structural heart disease. Strenuous physical exertion was associated with sudden death in 17 of 19 cases (0.017 deaths per 50,000 exercise-hours), and the most frequent underlying etiology was myocarditis. Sudden cardiac death, a rare event in healthy young adults, is usually associated with exertion.
Adolescent↗
Purification of charybdotoxin, a specific inhibitor of the high-conductance Ca2+-activated K+ channel.
Charybdotoxin is a high-affinity specific inhibitor of the high-conductance Ca2+-activated K+ channel found in the plasma membranes of many vertebrate cell types. Using Ca2+-activated K+ channels reconstituted into planar lipid bilayer membranes as an assay, we have purified the toxin from the venom of the scorpion Leiurus quinquestriatus by a two-step procedure involving chromatofocusing on SP-Sephadex, followed by reversed-phase high-performance liquid chromatography. Charybdotoxin is shown to be a highly basic protein with a mass of 10 kDa. Under our standard assay conditions, the purified toxin inhibits the Ca2+-activated K+ channel with an apparent dissociation constant of 3.5 nM. The protein is unusually stable, with inhibitory potency being insensitive to boiling or exposure to organic solvents. The toxin's activity is sensitive to chymotrypsin treatment and to acylation of lysine groups. The protein may be radioiodinated without loss of activity.
Amino Acids↗
Serum albumin and the metabolism of disulfiram.
The effectiveness of tetraethylthiuram disulfide (DSF) as a drug used in the treatment of alcohol abuse has been limited by the fact that it is degraded rapidly in the tissues and in the serum. Hence, a useful dose-response curve for this drug cannot be determined easily. The degradation in the tissues has been well characterized; however, its fate in the serum is less well understood. Here we kinetically describe the first steps in the degradation of DSF in the serum which results from a covalent interaction of this drug with the free sulfhydryl of serum albumin. DSF and its cleavage product diethyldithiocarbamate (DDC) both absorb significantly in the ultraviolet region. The reduction of DSF with mercaptoethanol to two molecules of DDC resulted in a large change in absorption in this region. The reaction of serum albumin with DSF produced a similar but much slower change in the ultraviolet absorption. As a result of the existence of this slow spectral change, we have been able to directly and continuously monitor the interaction of serum albumin and DSF and have determined that it is an overall first-order process. A model is proposed wherein DSF and serum albumin rapidly form a noncovalent adduct and, subsequently, in a slow unimolecular process, DSF is reduced to one mole of free DDC and one mole of the serum albumin-DDC mixed disulfide. At pH 9 the half-time for this process was 30 to 40 sec, and at pH 7.4 the half-time for this process was 1 to 1.5 min. These results suggest that degradation of DSF by serum albumin is physiologically and clinically important since the drug is maximally active only many hours after administration.
Disulfides↗
Measurement of breath carbon disulfide during disulfiram therapy by gas chromatography with flame photometric detection.
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Adult↗
Comparisons of copper deficiency states in the murine mutants blotchy and brindled. Changes in copper-dependent enzyme activity in 13-day-old mice.
The activity of two copper-dependent enzymes, cytochrome c oxidase and copper, zinc-superoxide dismutase, was determined in six tissues of age-matched (13-day-old) copper-deficient mutant and normal mice. In the two mutants 'brindled' and 'blotchy', brain, heart and skeletal muscle had significant enzyme deficiencies. Cytochrome c oxidase was more severely affected than was superoxide dismutase. In these three tissues the degree of deficiency could be correlated with decreased copper concentration; however, enzyme activity was normal in liver, kidney and lung, despite abnormal copper concentrations in these tissues. In nutritionally copper-deficient mice, all six tissues showed decreased enzyme activity, which was most marked in brain, heart and skeletal muscle, the tissues which showed enzyme deficiencies in the mutants. Analysis in vitro of cytochrome c oxidase (temperature coefficient = 2) at a single temperature was found to underestimate the deficiency of this enzyme in hypothermic copper-deficient animals. Cytochrome c oxidase deficiency may therefore be sufficiently severe in vivo to account for the clinical manifestations of copper deficiency. An injection of copper (50 micrograms of Cu+) at 7 days increased cytochrome c oxidase activity by 13 days in all deficient tissues of brindled mice, and in brain and heart from blotchy mice. However, skeletal-muscle cytochrome c oxidase in blotchy mutants did not respond to copper injection. Cytochrome c oxidase activity increased to normal in all tissues of nutritionally copper-deficient mice after copper injection, except in the liver. Hepatic enzyme activity remained severely deficient despite a liver copper concentration three times that found in copper-replete controls. Superoxide dismutase activity did not increase with treatment in either mutant, but its activity was higher than control levels in nutritionally deficient mice after injection. This difference is probably due to sequestration of copper in mutant tissue such as kidney, but a defect in the copper transport pathway to superoxide dismutase cannot be excluded.
Animals↗
The nucleotide sequence of three genes participating in the adipose differentiation of 3T3 cells.
When 3T3 cells undergo adipose differentiation, they are reprogrammed by changes in gene expression of sufficient magnitude to greatly alter the protein composition of the cells. Three participating genes encode glycerophosphate dehydrogenase, a lipid-binding protein, and a serine protease. These three genes have now been cloned and sequenced. Their exon/intron structures are described, together with some interesting peculiarities and some regions of common sequence. It remains to be demonstrated whether the information for common participation of the genes in the program of differentiation resides in controlling elements within the regions sequenced.
Adipose Tissue↗
Squamous cell carcinoma in congenital ichthyosis with deafness and keratitis. A case report and review of the literature.
The first case of invasive squamous cell carcinoma (SCC) arising in the skin of a patient afflicted with keratitis, ichthyosis, and deafness (KID) syndrome is reported. A 35-year-old man, diagnosed as having KID syndrome in early childhood, developed bilateral fungating lesions on his feet. The entire left foot became involved with a multinodular fungating mass which proved to harbor a SCC, necessitating a left below-knee amputation. Although rare, KID syndrome can be associated with SCC of the skin.
Adult↗
Predictive power of the polygraph: can the "lie detector" really detect liars?
Expanded use of the polygraph as a detector of lies has been proposed in the United States and the United Kingdom. The positive predictive value of the polygraph (ie, the proportion of positive test results that are true positives) was assessed, on the evidence of the best published data for the sensitivity and specificity of the device. In many screening or investigative situations, the predictive value would be poor; most of the positive results would be false positives. Consequently, truthful persons incriminated as liars by the polygraph would outnumber actual liars with a positive result on the test.
Bayes Theorem↗
Radioimmunoassay for detection of the Snow Mountain Agent of viral gastroenteritis.
The Snow Mountain Agent (SMA) is a Norwalk-like viral agent of acute gastroenteritis that has been detected only by immune electron microscopy (IEM). We established a solid phase microtiter radioimmunoassay (RIA) for SMA antigen employing pre-and post-challenge sera from volunteer studies as capture antibodies. SMA was detected in 12 of 67 stool samples from volunteers who were ill after oral challenge with SMA. All samples in which virus particles were detected by IEM were positive by RIA, but the RIA was 10-80 times more sensitive than IEM. To detect serum antibody to SMA, a blocking test was developed, employing diarrheal stool containing SMA as a standard source of antigen. Serum antibody rises were detected in eight out of nine volunteers with experimentally induced illness following challenge with SMA, as well as in three out of three naturally occurring cases. A preliminary sero-epidemiologic survey suggested that infection with SMA was common in the population surveyed. This RIA should permit large scale seroepidemiologic studies of SMA to be carried out, and should also facilitate characterization of this agent.
Adolescent↗
Radionuclide evaluation of bile leakage and the use of subhepatic drains after cholecystectomy.
Our study addresses the question of efficacy of drainage after cholecystectomy by evaluation of the leakage of radiolabeled bile. Based on our data, drains placed at the time of surgery do not appear to reliably remove bile or to decrease morbidity. Our study reveals that bile leakage after cholecystectomy is frequent, cannot be accurately predicted at operation, is not related to the experience of the operating surgeons, and does not necessarily correlate with morbidity. The shorter postoperative hospital stay in the group of patients with subhepatic bile leakage compared with the group without evidence of leakage after cholecystectomy is not statistically significant. However, this trend does suggest that there is no increase in morbidity associated with bile leakage per se. A large, clinically significant bile leak can easily be treated by modern interventional radiologic techniques if drainage is indicated. A larger, double-blind study is necessary to further evaluate the issues surrounding bile leakage and drainage after cholecystectomy.
Adult↗
Primary malignant lymphoma of urinary bladder.
A case of primary malignant lymphoma of the urinary bladder is described. The classic presentation of gross hematuria and dysuria with a benign clinical course is illustrated. From a review of the literature and our experience, we conclude that localized primary lymphoma of the bladder, especially those with favorable histologic findings, often does not require medical or surgical intervention. Persistent irritative bladder symptoms can be palliated adequately with external beam radiotherapy, while surgical intervention is rarely indicated.
Aged↗
A practical and effective protocol for the post angiographic management of patients with critical stenosis of the left main coronary artery.
The management of newly diagnosed left main obstruction varies throughout institutions. At some Centers, very aggressive measures including intra-aortic balloon counterpulsation and emergent revascularization are routine protocol. Twenty consecutive patients with greater than 50% luminal narrowing of the left main coronary artery were treated over a 1 year period. Routine post catheterization protocol for 19 patients included intensive care observation, continuation of nonparenteral anti-anginal agents, and coronary revascularization within 24 hours of diagnosis. One patient experienced severe hemodynamic embarrassment at the time of catheterization and underwent emergency coronary bypass. All patients were discharged uneventfully following successful surgery. Based on this experience, it is felt that with surgical support, patients with significant left main stenosis can be treated with standard anti-anginal therapy, and undergo elective revascularization without complications.
Adult↗
The Norwich Quakers: some links with pharmacy and medicine.
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History of Pharmacy↗
Remembering a pharmaceutical baron--Jesse Boot.
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History of Pharmacy↗
Computer-assisted assessment of the fetal biophysical profile.
The biophysical profile assesses fetal heart rate, breathing movements, fetal body movements, amniotic fluid volume, and fetal tone. In the past, these data have been scored by an arbitrary, unweighted system. While this approach is useful in detecting major anomalies and oligohydramnios, both static observations, the dynamic variables (fetal heart rate, fetal breathing movements, and fetal body movements) have added little information beyond that of an extended nonstress test alone. We have evaluated an alternative biophysical assessment system, modeled after extended physiologic studies, which not only acquires dynamic fetal variables simultaneously but, with computer assistance, quantifies the biophysical information. With an ADR 4000/L scanner, a Hewlett-Packard 8040 A monitor, and a specially programmed IBM microcomputer, we studied 100 normal term fetuses during 60-minute epochs. Each gestation had normal amniotic fluid volume and fetal tone. Normative values for the dynamic variables, expressed as means +/- SD were: fetal heart rate, 137 +/- 6.3 bpm; incidence of fetal breathing movements, 25.0% +/- 17.3%; rate of fetal breathing movements, 46.0 +/- 9.4 breaths/min; total fetal breathing movements, 823 +/- 61; incidence of fetal body movements, 8.5% +/- 3.9%; accelerations (greater than 15 bpm, 15 seconds), 14.1 +/- 6.3. We conclude that this approach is practicable, respects the biologic cycles of fetal behavior, and provides a basis for population standards and sequential study of the same fetus.
Amniotic Fluid↗