Definitions, methodology and therapeutic strategies in portal hypertension. A Consensus Development Workshop, Baveno, Lake Maggiore, Italy, April 5 and 6, 1990.
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Humans↗
Biomedical subjects
M Henderson
Publications and source records attributed to M Henderson.
Con A-induced suppressor cell function depends on the activation of the CD4+CD45RA inducer T cell subpopulation.
Human T cells incubated for 48 hr with Con A suppress B cell Ig production. We sought to define the interactions between CD4+ T cells and CD8+ T cells in the generation of suppressor cell activity following Con A stimulation. Con A-activated CD4+ inducer T cells suppressed Ig production in autologous cocultures of T cells and B cells by 84%, while PHA-activated CD4+ T cells could not. However, Con A-activated CD4+ T cells are not themselves suppressors. When Con A-activated CD4+ T cells were added to coculture of B cells plus T cells depleted of CD8+ T cells, no suppression of Ig production was observed. Furthermore, these Con A-activated CD4+ T cells were able to provide excellent help for Ig production. Therefore, Con A-induced suppressor cell function requires a CD4+ suppressor/inducer acting on a CD8+ suppressor/effector ultimately resulting in the down regulation of B cell Ig synthesis. Human CD4+ inducer T cells can be functionally dissected into helper/inducer or suppressor/inducer T lymphocytes based on their expression of either the CDw29 or CD45RA surface molecules, respectively. Following incubation with Con A the expression of CD45RA on CD4+ T cells increased from 34 to 80% (P = 0.001) while CDw29 expression was unchanged. Incubating lymphocytes with PHA resulted in a non-specific increase in both CD45RA and CDw29 expression by CD4+ T cells. The increase in CD4+CD45RA expression was a result of active proliferation by the Con A-stimulated T cells. Suppression of Ig secretion was directly correlated with the enhanced CD45RA expression following Con A activation. We demonstrate that enhanced suppressor/inducer function is unique to Con A stimulation and was not observed following activation by PHA. Furthermore, short-term culture with Con A results in the selective expansion of the CD4+CD45RA T cell subpopulation.
Antigens, CD↗
Isolation and characterization of a novel liver-derived immunoinhibitory factor.
Cytosolic extracts prepared from perfused whole liver or purified hepatocytes of C57BL/6 mice inhibited interleukin-2--and concanavalin A--induced spleen cell proliferation in vitro. In contrast, cytosolic extracts from purified nonparenchymal liver cells had no effect. Arginase and very-low-density lipoprotein were previously identified as two immuninhibitory substances present in liver cytosolic extracts. We demonstrated, however, that inhibitory activity remained after removal of very-low-density lipoprotein and arginase from liver cytosolic extract by repeated ultracentrifugation and gel filtration chromatography, respectively, suggesting the presence of another inhibitor. Further purification by anion-exchange chromatography and chromatofocusing led to the isolation of a novel liver-derived immunohibitory factor. This liver-derived immunoinhibitory factor is sensitive to pronase digestion and heat and acid treatment; it has an estimated isoelectric point of 8.25. The Mr of liver-derived immunoinhibitory factor is 28 kD as estimated from its migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which is identical under both reducing and nonreducing conditions, indicating a monomeric nature of this protein. Amino acid composition analysis discloses that liver-derived immunoinhibitory factor is relatively rich in glycine and proline residues. Interleukin-2--induced spleen cell proliferation in vitro is inhibited by ths liver-derived immunoinhibitory factor, with a 50% inhibitory dose of 1.4 nmol/L. Furthermore, the biological activity of the liver-derived immunoinhibitory factor is not confined to mouse spleen cells, since the growth of B16 mouse melanoma and H35 rat hepatoma cells is also inhibited. A comparison with other liver-derived immunoinhibitors reported previously supports our claim that the liver-derived immunoinhibitory factor is a novel inhibitory protein.
Animals↗
Scottish cocaine users: wealthy snorters or delinquent smokers?
Ninety-two cocaine users were interviewed in Scotland. Most were middle-class nasal users, also used other drugs and generally gave cocaine a positive rating. One half of them had at some time used cocaine more than once a week. For some, this period lasted some months, when as much as 30 'lines' of cocaine were used per day of cocaine use. More of these heavy users reported adverse effects of cocaine than was the case for light users. Nonetheless, most heavy users had reduced their use by themselves to the point that their current cocaine use was no different from that of light users. Possible explanations for this apparently spontaneous reduction are discussed.
Adolescent↗
The impact of school-based drug education.
Outcome evaluation of the impact of drug education on a representative sample of 1197 pupils revealed no effects of drug education on drug-related behaviour or drug-related attitudes. However, drug education raised levels of drug-related knowledge. The long term implications of these findings would require further study. Comparison of process and outcome measures indicated that, with the exception of knowledge, teachers' positive views of drug education were misplaced. Critical aspects of good practice are discussed, both at the level of the individual teacher and in terms of whole-school factors.
Adolescent↗
Measuring the efficiency of an artificial lung: 1. Carbon dioxide transfer.
The performance of a hollow fibre artificial lung ('Capiox E') was analysed by measurement of the 'parallel deadspace' of the device under varying conditions in 21 patients. The efficiency with which carbon dioxide was exchanged was determined by the time available for equilibration between the blood and gas phases. When this equilibration coefficient was less than 12 seconds per litre of blood flow per litre of gas flow, there was a marked reduction in the efficiency of gas exchange. Under certain conditions, the 'counter-current' design of the device apparently permitted the clearance of carbon dioxide at a partial pressure greater than that which was found in the mixed venous blood. This anomalous behaviour may represent in vivo confirmation of the Haldane effect.
Adult↗
Sequestration of glyceryl trinitrate (nitroglycerin) by cardiopulmonary bypass oxygenators.
The effectiveness of glyceryl trinitrate (nitroglycerin) in controlling myocardial ischemia and blood pressure during coronary artery bypass graft surgery is frequently lost during surgery, possibly as a result of drug sequestration by the cardiopulmonary bypass circuit. The objective of this study was to utilize a gas-liquid chromatographic assay to determine the extent of removal of glyceryl trinitrate from the priming fluid by the bubble and membrane oxygenators. The apparatus was maintained at either 25 or 37 degrees C, the two extreme temperatures experienced by the patient during bypass surgery. At apparent steady state, the circulating glyceryl trinitrate concentration was decreased by 20.6%, 46.6%, and 67.3% with the Maxima membrane oxygenator, Cobe membrane oxygenator, and Bentley bubble oxygenator, respectively. The three-layer defoaming filters that are used in the Bentley bubble oxygenator were studied by immersing each of the three filters in fluid containing 60 nM glyceryl trinitrate and monitoring the drug concentration in Plasmalyte. The filters sequestered approximately 90% of the glyceryl trinitrate from the bathing solution of which 31% was recovered with a single methanol wash of the polyurethane filter. These data demonstrate that the different oxygenators used in the cardiopulmonary bypass circuit remove glyceryl trinitrate to varying degrees from the circulating fluid.
Cardiopulmonary Bypass↗
First-trimester prenatal diagnosis of tyrosinemia type I by amniotic fluid succinylacetone determination.
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Amino Acid Metabolism, Inborn Errors↗
Analysis of the costs of a large prevention trial.
Total direct costs of the Women's Health Trial (WHT), a large multicenter prevention trial, were reduced by more than 50% by means of research cost analysis conducted during the trial design phase. The unit costs of specific trial activities were estimated so that total direct costs of the trial could be predicted from design parameters. The relative costs of screening, treatment, and follow-up, and the fixed costs associated with each clinical center in a multicenter prevention trial were taken into account. Direct costs of the WHT were reduced from +195 million to +95 million by refinement of the trial protocol, selection of an efficient design, and consideration of trial logistics. The analyses suggest several ways to reduce costs in a prevention trial. Use of the case-cohort approach can reduce costs substantially when the protocol includes collection of specimens or data that are costly to process. When establishing and maintaining a clinical center represents a significant proportion of a clinical center's costs, use of a smaller number of larger clinical centers offers important cost savings. Because restrictive eligibility requirements reduce the recruitment potential of each clinical center, use of high-risk participants may not improve the efficiency of a prevention trial; its favorable impact on sample size may fail to compensate for its cost in terms of additional clinical centers and higher recruitment costs.
Aged↗
Two approaches to measuring quality in medical case management programs.
In a study of the quality of care in a medical case management program, five physician experts, applying criteria to medical records, found the care provided appropriate in a majority of 40 cases (10 each of head injury, spinal cord injury, high-risk infants, and AIDS). Nurses interviewing parents of 30 high-risk infants found general satisfaction with case management.
Adaptation, Psychological↗
Technology and outpatient review: a preliminary evaluation.
Most health care utilization and cost control programs focus on inpatient care or on high-cost, catastrophic illnesses or injuries. Recently, however, Parkside Health Management Corporation has developed a utilization review program that targets treatments and high-technology procedures performed primarily in an outpatient setting, as well as specific inpatient procedures not included in other review programs. These include chiropractic, podiatric, and physical therapy treatments; cesarean section; and endoscopy, ultrasound in pregnancy, and lithotripsy. The treatments/procedures examined in this program, called Technology and Outpatient Review (TOR), account for approximately 6% of claims expenses. Bigel Institute for Health Policy researchers are evaluating a pilot test to determine TOR's effect on health care costs and utilization, appropriateness, and patient satisfaction.
Ambulatory Care↗
Beyond the living will.
Sixty-three residents of a retirement community with living wills were studied to see if more specific planning for, and thus control over, their dying process would decrease their anxiety about death. The experimental group received intervention in the form of counseling and filling out a questionnaire regarding specific treatments (e.g., CPR, feeding tubes), proxy decision making, and other related questions. Results show that the mean death anxiety score for the experimental group decreased, whereas the control group's mean score did not change significantly.
Aged↗
An evaluation of BSE frequency and quality and their relationship to breast lump detection.
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Aged↗
Changes in food patterns during a low-fat dietary intervention in women.
The Women's Health Trial was initiated by the National Cancer Institute to study the effects of a low-fat diet on the incidence of breast cancer in women at elevated risk for the disease. The purpose of this article is to examine the specific dietary changes that 173 women made while participating in a feasibility intervention program to reduce their fat intake to approximately 20% of total calories over a 12-month period. The intervention program used group sessions to teach nutrition information and behavioral skills necessary to make a life-style dietary change. Four-day food records were collected from participants at the beginning of the study and again at 12 months. Women in the intervention group reduced their total fat intake from a mean of 76 gm (39% of total energy) to 31 gm (22% of total energy), mainly by decreasing their fat intake from milk products, red meats, and fats/oils. These women used cheddar cheese, American cheese, whole milk, butter, mayonnaise, salad dressing, bacon, and hamburgers less frequently, and used diet American cheese, low-fat cottage cheese, and skim milk more frequently. They consumed less fat in their vegetable dishes, and their total caloric intake from fruit increased slightly. In addition, the overall quality of the diets improved, since there was a 20% to 50% increase in the energy-adjusted intake of vitamins and minerals from food sources.
Aged↗
Major increases in spermidine/spermine-N1-acetyltransferase activity by spermine analogues and their relationship to polyamine depletion and growth inhibition in L1210 cells.
As an antiproliferative strategy, we are using bis(ethyl) derivatives of spermine to suppress polyamine biosynthetic enzyme activity and, thereby, deplete intracellular polyamine pools. Since certain of these analogues have recently been shown to potently increase spermidine/spermine-N1-acetyltransferase activity, we have investigated the relationship of this effect to growth inhibition and polyamine depletion. The cellular effects of N1,N12-bis(ethyl)spermine (BESPM) and two of its homologues, N1,N11-bis(ethyl)norspermine (BENSPM) and N1,N14-bis(ethyl)homospermine (BEHSPM), were compared in L1210 cells following treatments at equimolar concentrations (2 microM) and at concentrations (0.5 microM BEHSPM; 2 microM BESPM, and 20 microM BENSPM) producing comparable intracellular concentrations (2600-3000 pmol/10(6) cells) of the analogues. At 2 microM, BENSPM increased total polyamine N-acetyltransferase activity by 15-fold, BESPM, by 7-fold, and BEHSPM, by only 1.5-fold. These differences were much more exaggerated at comparable intracellular concentrations, where BENSPM increased enzyme activity 31-fold, BESPM, 7-fold, and BEHSPM had no effect. This rank order in effectiveness sharply contrasted effects on cell growth and interference with polyamine biosynthesis, which correlated more with intracellular accumulation of the analogues. At 2 microM, BEHSPM was most effective in suppressing ornithine and S-adenosylmethionine decarboxylases, depleting polyamine pools, and inhibiting cell growth, followed by BESPM and then by BENSPM. Thus, the data indicate that, in L1210 cells, the large increases in spermidine/spermine-N1-acetyltransferase activity produced by the analogues do not appear to contribute significantly to polyamine depletion or to be causally related to inhibition of cell growth. These studies also identify BENSPM as the most potent modulator of spermidine/spermine-N1-acetyltransferase activity thus far studied in cell culture systems. To a large extent, its greater effectiveness over BESPM seems to be attributable to a major increase in prolongation of enzyme half-life (3.9 versus 1.3 h), presumably due to enzyme stabilization caused by differential binding of the analogues at the enzyme active site.
Acetyltransferases↗
Causal relation between the pressure gradient and left ventricular ejection time in hypertrophic cardiomyopathy.
This study was designed to evaluate the relation between severity of obstruction to left ventricular outflow and left ventricular ejection time in hypertrophic obstructive cardiomyopathy. With dual catheters across the left ventricular outflow tract, the pressure gradient and corresponding left ventricular ejection time were measured in 10 patients as the pressure gradient was pharmacologically provoked or abolished, or both. The patients were studied during constant atrial pacing to avoid the potential errors introduced with heart rate correction equations. The pressure gradient was pharmacologically provoked or reduced over a range of greater than or equal to 62 mm Hg per patient. In each patient the left ventricular ejection time varied directly with the pressure gradient (mean r = 0.97, range 0.92 to 1.00). The change in magnitude of the pressure gradient varied directly with the corresponding change in the measured ejection time (mean r = 0.98, range 0.97 to 1.00). When the data from all 10 patients were pooled with use of Weissler's heart rate correction equation, the relation between the corrected left ventricular ejection time and the pressure gradient was still significant and linear (r = 0.86), but less so than in individual patients. This difference was the result of marked interpatient variability in the slope of this linear relation reflecting interpatient differences in other important factors, such as underlying myocardial contractility and stroke volume, that influence left ventricular ejection time. This study demonstrates a clear, direct and highly significant relation between the magnitude of the pressure gradient and the left ventricular ejection time in hypertrophic obstructive cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac Catheterization↗
Mutations in nuclear gene cyt-4 of Neurospora crassa result in pleiotropic defects in processing and splicing of mitochondrial RNAs.
The nuclear cyt-4 mutants of Neurospora crassa have been shown previously to be defective in splicing the group I intron in the mitochondrial large rRNA gene and in 3' end synthesis of the mitochondrial large rRNA. Here, Northern hybridization experiments show that the cyt-4-1 mutant has alterations in a number of mitochondrial RNA processing pathways, including those for cob, coI, coII and ATPase 6 mRNAs, as well as mitochondrial tRNAs. Defects in these pathways include inhibition of 5' and 3' end processing, accumulation of aberrant RNA species, and inhibition of splicing of both group I introns in the cob gene. The various defects in mitochondrial RNA synthesis in the cyt-4-1 mutant cannot be accounted for by deficiency of mitochondrial protein synthesis or energy metabolism, and they suggest that the cyt-4-1 mutant is defective in a component or components required for processing and/or turnover of a number of different mitochondrial RNAs. Defective splicing of the mitochondrial large rRNA intron in the cyt-4-1 mutant may be a secondary effect of failure to synthesize pre-rRNAs having the correct 3' end. However, a similar explanation cannot be invoked to account for defective splicing of the cob pre-mRNA introns, and the cyt-4-1 mutation may directly affect splicing of these introns.
Blotting, Northern↗