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Biomedical subjects

J Allen

Publications and source records attributed to J Allen.

At least 37 records · Page 2Linked to original sources

Quality of care and cost-containment in managed mental health: policy, education, research, advocacy.

Managed mental health care cost-containment practices of risk-benefit analysis, provider usage, manipulation of supply and demand, gate keeping, medical necessity, and formulation have adversely affected quality of care. Improved mental health services are dependent upon redefining mental health problems and understanding inequities created by medicalization as means to limit access to services. This dilemma can be addressed by development of mental health policy, public education, and political advocacy. An immediate role for professional psychology is found in the creation of a research agenda that documents empirically supported interventions for specific mental health problems, mechanisms of effective and acceptable service-delivery, and identification of providers with demonstrated clinical skills, including cultural competencies.

Cost Control

Replication and extension of Marlatt's taxonomy of relapse precipitants: overview of procedures and results. The Relapse Research Group.

The Relapse Replication and Extension Project (RREP) was a multisite study to replicate and extend Marlatt's taxonomy of relapse precipitants. In addition to replicating Marlatt's original taxonomic system, three independent research teams utilized prospective designs to identify additional predictors of relapse and developed and evaluated two alternative systems for assessing high risk relapse situations. This overview describes the replication methodology, summarizes seven RREP studies completed by the three research groups, and discusses five cross-cutting conclusions emerging from the studies. These conclusions are: (1) reliability of Marlatt's taxonomic system was variable both within and across the three research sites; (2) Marlatt's taxonomic system showed little predictive validity in analyses that used pretreatment relapse data to predict post-treatment relapse, but there are important unresolved issues; (3) an alternative taxonomy provided little more predictive validity than the original taxonomy even though it measured more dimensions of relapse situations and provided greater analytic flexibility; (4) the Reasons for Drinking Questionnaire appeared to be a successful psychometric transformation of Marlatt's taxonomy, one which did demonstrate predictive validity; and (5) Marlatt's taxonomy was based on a time-intensive model of relapse prediction whereas RREP prospective analyses represented time-extensive models of relapse prediction. Coping responses are noted to be effective predictors of relapse under both models.

Adult

Linguistic aspects of speech synthesis.

The conversion of text to speech is seen as an analysis of the input text to obtain a common underlying linguistic description, followed by a synthesis of the output speech waveform from this fundamental specification. Hence, the comprehensive linguistic structure serving as the substrate for an utterance must be discovered by analysis from the text. The pronunciation of individual words in unrestricted text is determined by morphological analysis or letter-to-sound conversion, followed by specification of the word-level stress contour. In addition, many text character strings, such as titles, numbers, and acronyms, are abbreviations for normal words, which must be derived. To further refine these pronunciations and to discover the prosodic structure of the utterance, word part of speech must be computed, followed by a phrase-level parsing. From this structure the prosodic structure of the utterance can be determined, which is needed in order to specify the durational framework and fundamental frequency contour of the utterance. In discourse contexts, several factors such as the specification of new and old information, contrast, and pronominal reference can be used to further modify the prosodic specification. When the prosodic correlates have been computed and the segmental sequence is assembled, a complete input suitable for speech synthesis has been determined. Lastly, multilingual systems utilizing rule frameworks are mentioned, and future directions are characterized.

Communication

Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-oncogene leads to compensatory activation of Pim-2.

The Pim-1 proto-oncogene is one of the most potent collaborators of the myc proto-oncogenes in inducing lymphomagenesis in mice. Contrary to the profound effects when overexpressed in vivo, Pim-1-deficient mice showed only subtle phenotypic alterations, which could indicate the presence of redundantly acting genes. In line with this, a PCR-based screen has led to the identification of a closely homologous gene, Pim-2. The X-linked Pim-2 gene is 53% identical to Pim-1 at the amino acid level and shares substrate preference and the usage of non-AUG initiation codons with Pim-1. We have used these data to test whether the strong synergistic interaction between Pim-1 and c-myc can be utilized to gain access to Pim-1 compensatory pathways. We reasoned that, upon proviral tagging in compound mutant mice (E mu-myc/Pim-1-/- mice), the selective advantage of cells carrying provirally activated genes, that act downstream from or parallel to Pim-1, would increase. We show here that this is the case. A dramatic increase (from 15 to 80%) was found in the frequency of proviral activation of the Pim-2 gene. These data show that the described strategy of 'complementation tagging' represents a powerful new tool to identify components of pathways involved in processes as complex as multistep tumorigenesis.

Amino Acid Sequence

Binding of [3H]cirazoline to an imidazoline site in rat brain and kidney membranes.

Two classes of high-affinity sites for [3H]cirazoline were characterized in rat brain and kidney membranes. In both tissues, the binding parameters for the high- and low-affinity sites are similar with Bmax values of approximately 50 fmol/mg protein, Kd approximately 0.6 nM and Bmax approximately 470 fmol/mg protein, Kd approximately 11 nM respectively. Inhibition studies of [3H]cirazoline binding to the lower affinity site revealed that only guanidinium or imidazoline derivatives compete with the specific binding of this radioligand. Our results suggest that [3H]cirazoline could be used as a novel ligand to label the non-adrenergic imidazoline-preferring sites.

Animals

CD36 gene transfer confers capacity for phagocytosis of cells undergoing apoptosis.

Phagocyte recognition and ingestion of intact cells undergoing apoptosis are key events in this generally important program of cell death. Insufficient phagocyte capacity for apoptotic cells can result in failure to clear dying cells before membrane integrity is lost, resulting in leakage of noxious cell contents and severe tissue damage. However, no means has been available to increase phagocytic clearance of apoptotic cells. We now report that transfection of the macrophage adhesion molecule CD36 into human Bowes melanoma cells specifically conferred greatly increased capacity to ingest apoptotic neutrophils, lymphocytes, and fibroblasts, comparable to that exhibited by macrophages. Furthermore, when CD36 was transfected into another cell type with limited capacity to take up apoptotic bodies, the monkey COS-7 cell, similar effects were observed. Therefore, CD36 gene transfer can confer "professional" capacity to ingest apoptotic cells upon "amateur" phagocytes.

Animals

Biosphere 2.

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Ecological Systems, Closed

Modulation of cell phenotype in human osteoblast-like cells by the simian virus 40.

At present, the majority of in vitro research into bone metabolism is performed on either primary cultures of bone or osteosarcoma lines. A better model of the behaviour of normal bone cells would be a cell line derived from normal, adult bone that retained osteoblast-like characteristics. We infected a culture of bone cells from adult humans with simian virus 1613, a variant of the simian virus 40, and obtained 12 clones of variable morphology. The clones were maintained in culture for as long as 6 months. Population doubling times, synthesis of alkaline phosphatase and osteocalcin, secretion of mineral, morphology, and ability to withstand freezing were examined. SV/EC cell morphology varied from the polygonal, osteoblast-like to the bipolar, fibroblast-like. Population doubling times ranged from 0.55 to 2.8 days (compared with 3.9 days for the nontransformed human osteoblast-like cells). Synthesis of alkaline phosphatase varied but was less than that by the human osteoblast-like cells. With the exception of clone 11, all of the transformed clones synthesised mineral in vitro under mineralising conditions. Four clones showed increased synthesis of alkaline phosphatase and increased population doubling times after passaging. All of the clones were successfully frozen and thawed, but, unlike normal human osteoblast-like cells, none responded to stimulation with parathyroid hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase

Prenatal diagnosis of galactosemia.

The experience from three different European centres with the prenatal diagnosis of galactose-1-phosphate-uridyltransferase (GALT) deficiency is presented and the question whether or not there is a need for prenatal diagnosis of this disorder is discussed. Most prenatal diagnoses (n = 50) have been performed by assay of GALT activity in cultured amniotic fluid cells. The assay used is reliable and clearly distinguishes homozygous affected fetuses (n = 11; 0%-2.3% of mean control enzyme activity) from non-(homozygous)-affected fetuses. The GALT assay for cultured amniocytes was adapted to assay the enzyme directly in chorionic villi. The experience with chorionic villi comprises 23 cases with 5 affected fetuses (0%-4.2% of mean control enzyme activity). In 36 cases galactitol was determined in amniotic fluid supernatant by gas chromatography-mass spectrometry. This method also differentiated affected (n = 11; galactitol 5.9-10.6 mumol/l) and unaffected pregnancies (galactitol 0.23-1.6 mumol/l) clearly and has the advantage of providing a result within a day or two after amniocentesis. Prenatal diagnosis of galactosemia is undertaken rarely and sometimes for the wrong reasons, but it should perhaps be considered more seriously until better methods of treatment are established.

Amniocentesis

Small dishwashers for hospital ward kitchens.

A comparison of the cleaning efficiency and thermal disinfection capabilities of 12 small dishwashers being used in hospital wards was carried out. Machines installed prior to the establishment of a local purchase policy failed to achieve the standards required for hygienic washing up. Machines conforming to the purchasing criteria gave a satisfactory performance.

Cooking and Eating Utensils

Aneuploidies and micronuclei in the germ cells of male mice of advanced age.

The objective of this research was to determine whether the frequencies of chromosomally defective germ cells increased with age in male laboratory mice. Two types of chromosomal abnormalities were characterized: (1) testicular spermatid aneuploidy (TSA) as measured by a new method of multi-color fluorescence in situ hybridization (FISH) with DNA probes specific for mouse chromosomes X, Y and 8, and (2) spermatid micronucleus (SMN) analyses using anti-kinetochore antibodies. B6C3F1 mice (aged 22.5 to 30.5 months, heavier than controls but otherwise in good health) showed significant approximately 2.0 fold increases in the aneuploidy phenotypes X-X-8, Y-Y-8, 8-8-X and 8-8-Y with the greatest effects appearing in animals aged greater than 28 months. No age effect was observed, however, in X-Y-8 hyperhaploidy. Major age-related increases were seen in Y-Y-8 and X-X-8 hyperhaploidies suggesting that advanced paternal age is associated primarily with meiosis II rather than meiosis I disjunction errors. A approximately 5 fold increase was also found in the frequency of micronucleated spermatids in aged mice when compared with young controls. All micronuclei detected in the aged animals lacked kinetochore labeling, suggesting that they either did not contain intact chromosomes or the chromosomes lacked detectable kinetochores. The findings of the TSA and SMN assays are consistent with meiotic or premeiotic effects of advanced age on germ cell chromosomes, but there were differences in the age dependencies of aneuploidy and micronuclei. In summary, advanced paternal age may be a risk factor for chromosomal abnormalities (both aneuploidy and structural abnormalities) in male germ cells.

Aging

Poor fertilization may be related to oocyte or zona pellucida recognition defects specific to certain hyperstimulation regimens and limited to some males but not others: a case report.

OBJECTIVE: To determine if the controlled ovarian hyperstimulation (COH) regimen may cause sperm to appear subfertile only to improve considerably by changing the COH protocol. DESIGN: Case report with retrospective review of previous fertilization rates according to COH protocol used. MAIN OUTCOME MEASURES: Fertilization and pregnancy rates (PRs) after IVF-ET. RESULTS: Known fertile donor sperm failed to fertilize any of 11 oocytes compared with 14 of 18 for processed retrograde ejaculate using the same oocyte pool. Retrospective analysis of other cycles for different female patients but same donor found 16.6% fertilization rate whenever luteal phase leuprolide acetate (LA)-hMG regimen was used compared with 70.6% with short-flare regimen. CONCLUSION: Some COH regimens may cause oocyte or zona pellucida changes that create recognition defects for some sperm but not others. Interestingly, the sperm with the binding defect with the luteal phase LA-hMG COH protocol exhibited good fertilization rates with oocytes prepared with the short-flare protocol and demonstrated high in vivo PRs after IUI.

Adult

Body surface ECG potential maps in acute myocardial infarction.

An algorithm for the early detection of acute myocardial infarction (MI) using body surface electrocardiographic potential mapping has been developed. The mapping system consists of a 64-hydrogel electrode harness applied rapidly to the anterior chest, from which electrocardiographic signals are stored on a memory card and processed by computer. At each of the 64 points, QRS and ST-T isointegrals and 10 other features of the QRST segment are measured. Using these measurements, new variables are derived that express the shape of the three-dimensional geometric surface of the map. The isointegrals, features, and shape variables are used in a variety of techniques to discriminate between MI and control subjects. Maps were recorded from 69 patients at initial presentation of chest pain suggestive of acute MI and from 80 healthy control subjects. Using a multiple logistic regression technique, 14 variables were identified that correctly classified 79 of the 80 control subjects (specificity, 98.8%) and 65 of the 69 MI patients (sensitivity, 94.2%). The algorithm based on these 14 variables was applied prospectively to maps recorded on a further 48 control subjects and 59 patients with acute MI. Of the MI patients, 31 had inferior, 13 inferoposterior, 10 anterior, 2 posterior, 1 lateral, 1 inferior with right bundle branch block, and 1 anterior non Q wave MI. The algorithm correctly classified all 48 control subjects (specificity, 100%) and 57 of the 59 MI patients (sensitivity, 96.6%). Marked differences in the three-dimensional geometric map surfaces between the control subjects and MI patients were demonstrated. Variables derived from these surfaces form the basis of an algorithm with a high sensitivity and specificity for the automated detection of acute MI. The design of adaptive algorithms and their application to patients with chest pain and atypical electrocardiographic changes, particularly ST depression, may lead to the earlier detection of MI and greater numbers of patients receiving thrombolytic therapy.

Adolescent

Prospective assessment of an artificial neural network for the detection of peripheral vascular disease from lower limb pulse waveforms.

The diagnostic performance of an artificial neural network pulse classification system for the detection of peripheral vascular disease was investigated prospectively. Lower limb photoelectric plethysmographic pulses, and Doppler ankle/brachial pressure index (ABPI) measurements (pre- and post-exercise) were obtained from 200 patients referred to a vascular investigation laboratory. A single toe pulse was processed and used as input data to a neural network which had been trained previously with a set of pulses from 100 legs. The neural network outputs represented the diagnostic arterial disease classifications defined by the ABPI. From the 200 patients entered prospectively, 266 legs were available for neural network assessment. A network sensitivity of 92% and specificity of 63% were achieved with a diagnostic accuracy of 80%. By using a higher confidence for the classification decision a small, but insignificant overall improvement was obtained. When a borderline classification was introduced 100% sensitivity and 100% negative predictive value were obtained, though 31% of legs were unclassifiable. Nevertheless, the very high sensitivity and negative predictive value could make this quick and simple technique the one of choice for the first stage in screening large numbers of subjects.

Adult

The localization of the target antigens and antibodies in linear IgA disease is heterogeneous, and dependent on the methods used.

Fifty-nine patients with linear IgA disease, 24 with onset in childhood and 35 with adult onset, were studied. Sera from all patients were tested by indirect immunofluorescence, using as substrates intact normal skin and normal skin which had been split through the lamina lucida region of the basement membrane zone by suction and by prolonged incubation with molar NaCl. This enabled the site of the target antigen for the circulating IgA antibodies to be determined. The sites of deposition of the IgA antibodies in vivo were detected by raising a suction blister in eight patients, and splitting seven patients' biopsies by prolonged incubation with molar NaCl. Eighteen sera were positive with intact skin, and 34 with split skin. Twenty-nine sera were positive with suction blisters as substrate; 14 bound to the epidermal aspect of the split skin, seven in a combined pattern (binding to the epidermis and dermis) and six to the dermal aspect. Thirty-one sera bound to salt-split skin, 24 to the epidermal side and seven on the dermal side. There was discordance between the two methods of skin splitting in 15 sera. Seven sera gave a combined pattern with suction but with salt-split skin, five of these bound epidermally, one was dermal, and one negative. Five sera showed epidermal binding on salt-split skin and were negative on suction blisters, and the reverse was seen with one serum. Two sera gave variable results on suction blisters. Direct immunofluorescence studies showed dermal binding on all eight patients with suction blisters, and epidermal binding in four and dermal binding in three patients with salt splitting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent