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Biomedical subjects

P Bean

Publications and source records attributed to P Bean.

At least 55 records · Page 3Linked to original sources
PubMed1996

Carbohydrate-deficient transferrin evaluation in dry blood spots.

The aim of this study was to assess the performance of the isoelectric focusing/immunoblotting/laser densitometry (IEF/IB/LD) procedure to evaluate carbohydrate-deficient transferrin (CDT) derived from dry blood spots. Serum specimens obtained from insurance applicants were analyzed for CDT by IEF/IB/LD. Dry blood spots derived from 50 serum specimens were analyzed by IEF/IB/LD. A comparative analysis of these serum specimens and the paired dry blood spots by IEF/IB/LD shows a highly significant correlation of the CDT values (r = 0.94, p < 0.0001). Stability studies indicate that, under proper storage conditions (2-3 days at room temperature, 2 weeks at 4 degrees C, or frozen at or below -20 degrees C indefinitely), dry blood spots can be used as a source of CDT for analysis by IEF/IB/LD, thus simplifying sampling, storage, and transportation of specimens to the testing site.

Alcoholism↗
PubMed1995

Readmission study leads to continuum of care.

A "continuum of care" project has been developed with the goal of decreasing the rate of unplanned readmissions. In addition to reducing these readmissions from 5.0% to 3.45% annually, the project has fostered excellent communication among nurses, social workers and physicians. Also, many patients are communicating more effectively with their health care providers. Our patient care delivery system has become an integrated, collaborative model through meeting patient care needs beyond the walls of our facility.

Communication↗
PubMed1995

Carbohydrate-deficient transferrin and false-positive results for alcohol abuse in primary biliary cirrhosis: differential diagnosis by detection of mitochondrial autoantibodies.

Primary biliary cirrhosis (PBC) is one of the few nonalcohol-induced liver pathologies that causes false positives in assays of carbohydrate-deficient transferrin (CDT) for diagnosing alcohol abuse. CDT was quantified by isoelectric focusing-immunoblotting-laser densitometry (IEF-IB-LD) analysis of serum from 117 women: 57 PBC patients, 20 alcohol abusers, and 40 healthy donors. Only 5% (3 of 57) of PBC patients were positive at the densitometric cutoff value chosen (> 90% specificity). Serum samples from 15 PBC patients were further evaluated by IEF-IB-LD and CDTect chromatography-RIA. Receiver-operating characteristic (ROC) analysis showed that IEF-IB-LD better discriminated between PBC and alcohol abuse than CDTect did. By ROC analysis, mitochondrial autoantibodies to pyruvate dehydrogenase antigen M2 detected by enzyme immunoassay yielded optimal test performance for diagnosing PBC. Of six patients falsely positive for CDT by CDTect, five (83%) tested M2-positive. Thus, abnormal CDT results should be further evaluated by mitochondrial antibody testing in patients with findings compatible with PBC.

Alcoholism↗
PubMed1994

The use of the 'Appropriate Adult' Scheme (a preliminary report)

Details of a research study, funded by MENCAP, on the use of Appropriate Adults are given. A great deal of attention has been given recently to diverting the mentally disordered from the criminal justice system. This preliminary report discusses what happens to those who stay in the system--i.e. who are kept in police custody and eventually appear at court. Facilities are available under the Appropriate Adult Scheme for offenders seen to be mentally disordered or handicapped to have with them a 'responsible person' when they are interrogated by the police. The questions now posed are: does such a scheme work, and is the offender given protection under it?

Adult↗
PubMed1994

Allelic D variants of transferrin in evaluation of alcohol abuse: differential diagnosis by isoelectric focusing-immunoblotting-laser densitometry.

In the diagnosis of alcohol abuse transferrin (Tf) allelic D variants generate false-positive test results for carbohydrate-deficient transferrin (CDT) as assessed by their electrophoretic migration patterns. The predominant Tf C1 allele encodes a protein for which the most prevalent isoform has a pI of 5.4, i.e., four sialic acids and two bound ion molecules. Carriers of allele D encode Tfs with different amino acid sequences, for which the pI is > 5.7, despite their identical iron and carbohydrate composition. We used isoelectric focusing, immunoblotting, and laser densitometry (IEF-IB-LD) to distinguish Tf D variants from CDT. Alcohol abusers carrying the D chi allele tested CDT+; D chi nondrinkers were CDT-. Although normal controls (< 15 g of alcohol per day for 7-10 consecutive days) carrying variants D1, D2, or D chi exhibited abnormal IEF banding patterns, they did not generate false-positive results for CDT. D3 variants expressed isoforms that migrate at the same pI as CDT bands. Thus, IEF-IB-LD yields a highly resolved banding pattern to distinguish most Tf D variants from CDT.

Alcoholism↗
PubMed1994

Two methods for measuring carbohydrate-deficient transferrin in inpatient alcoholics and healthy controls compared.

Carbohydrate-deficient transferrins (CDTs), naturally occurring glycosylated transferrin proteins, are reported to be increased in the serum of individuals who consume large quantities of alcohol (ethanol). We compared two methods for the separation and quantification of CDT, using the same alcohol-dependent patients and age-, gender-, and race-matched controls as sources of samples for both assays. There was good correlation (r = 0.89) between the microcolumn anion-exchange chromatography/RIA (MAEC/RIA) procedure and the isoelectric focusing, immunoblotting, and laser densitometry (IEF/IB/LD) procedure. Receiver operating characteristic analysis suggested that the IEF/IB/LD procedure would perform slightly better than MAEC/RIA for the overall population. However, both assays were much more sensitive for the detection of heavy alcohol consumption in men, compared with women. Alcohol consumption in the week prior to CDT measurement correlated only weakly with the concentrations measured with either assay.

Adult↗
PubMed1993

A new approach to quantitate carbohydrate-deficient transferrin isoforms in alcohol abusers: partial iron saturation in isoelectric focusing/immunoblotting and laser densitometry.

Carbohydrate-deficient transferrin (Tf) represents a significant advance over previous markers of alcohol abuse. Isoelectric focusing (IEF) analysis of affinity-purified Tf, under conditions of total iron saturation, identifies a major isoform at pI 5.4 in both normal consumers and alcohol abusers; three additional Tf isoforms (pI 5.6, 5.7, and 5.8) are associated with alcohol abuse. Under conditions of partial iron saturation, IEF analysis of affinity-purified Tf reveals up to seven isoforms (pI range 5.3-6.0) common to normal consumers and alcohol abusers; three additional transferrin isoforms (pI range 6.1-6.3) are present in 68% (15/22) of the alcohol abuser specimens, but in only 8% (1/12) of the specimens from normal consumers and in none of the three specimens from abstainers. These three diagnostic bands comigrate with a set of defined Tf isoforms: human iron-free Tf containing two sialic acid residues, human sialic acid-free Tf with one iron molecule, and human sialic acid-free, iron-free Tf. Serum specimens from normal consumers and alcohol abusers, analyzed for Tf isoforms by an IEF-immunoblot method under conditions of partial iron saturation, expressed Tf isoforms similar to those found using affinity-purified Tf in standard IEF. Visual examination of the immunoblots reveals the diagnostic bands in 67% (32/48) of patients with histories of sustained alcohol abuse compared with only 17% (8/48) of the normal consumers. Scanning densitometry and volume integration analysis of the immunoblots representative of normal consumer and alcohol abuser populations results in mean (+/- SE) values of 4.1 +/- 0.8 and 19.3 +/- 3.6 units, respectively (p < 0.0002).

Adult↗
PubMed1992

Differential lysis of tumor target cells displayed by lymphokine activated killer (LAK) cell clones.

Lymphokine-activated killer (LAK) cells exhibit major histocompatibility complex (MHC) unrestricted cytolysis against a wide variety of fresh and cultured tumor cells. Because previous work from our laboratory suggested that trypsin treatment of unseparated populations of LAK cells had a differential effect on lysis of different tumors, in this report we analyzed the lytic specificity of LAK cell clones against a panel of three different targets: MCA, B16 and YAC-1. We found that 21 out of the 24 analyzed murine spleen and bone marrow clones killed a combination of two, but not all three, of these tumor cells. Determinations of the phenotype of 10 LAK cell clones showed six with rearrangements for the T cell receptor (TCR) beta chain gene, suggesting a T cell origin, and four with germ line configurations for the TCR beta and delta chain genes, a result consistent with a non-T cell lineage. This cloning procedure provided an experimental tool to develop new procedures of adaptive immunotherapy.

Animals↗
PubMed1992

Resistance of different tumor cells to lysis by lymphokine activated killer cells can be mediated by distinct mechanisms.

Lymphokine activated killer (LAK) cells have been shown to exert a potent cytotoxic effect on many histologically different tumors and virally infected targets. Most normal cells but very few tumors have proven resistant to LAK lysis. The availability of two LAK resistant tumors, P815r, a murine mastocytoma, and SNUC-1, a human colon carcinoma, allowed us to study the phenomenon of LAK lysis. We examined the role of surface molecules on targets, which mediate binding to LAK cells, by cold target competition experiments and lectin dependent cellular cytotoxicity assays. The results showed that in the murine system, P815r cells do not compete for lysis of the LAK sensitive target B16 whereas other LAK sensitive murine targets compete. Alternatively, in the human system, SNUC-1 cells compete for lysis of the LAK sensitive target SNUC-4 as do other LAK sensitive human tumor cells. Furthermore, inducing binding of target and effector cells with lectin reverted the resistance of P815r but not SNUC-1 targets to lysis by LAK cells. These results imply that distinct stages of the lytic pathway might be involved in the resistance of different tumors to killing by LAK cells. The murine cell line is resistant to lysis because it cannot bind LAK cells. The human target, which does bind LAK, was insensitive to the effects of tumor necrosis factor alpha (TNF-alpha), a lymphokine released by LAK effectors and possibly involved in their lysis. Resistance to TNF-alpha was not mediated by the presence of endogenous short-lived proteins in the SNUC-1 targets. The elucidation of mechanisms of resistance may provide a tool to improve current protocols of adoptive immunotherapy as well as insights as to how tumor cells are or are not killed by LAK effectors.

Animals↗
PubMed1990

Heterogeneity of cell surface structures involved in cytotoxicity mediated by lymphokine activated killer cells.

Lymphokine activated killer (LAK) cells mediate the lysis of a variety of histologically distinct tumor targets. We investigated the nature and diversity of the structures involved in the recognition phenomenon by evaluating the effects of treating effector and target cells with trypsin and chymotrypsin, enzymes that disrupt surface protein molecules. Chymotrypsin and trypsin treatment of B16 target cells, a murine melanoma cell line, significantly abolished killing by LAK cells. Alternatively, neither of these treatments in P815 cells, a murine mastocytoma cell line, affected killing by LAK cells. Moreover, we found a differential effect of both these enzymes on YAC-1 cells, a murine leukemia cell line, with trypsin having a less inhibitory effect on cytolysis than chymotrypsin. The nature of the LAK cell receptor that presumably plays a role in binding target antigen was also investigated. Treatment of LAK cells with chymotrypsin significantly reduced lysis of the B16 and YAC-1 target cell types. However, trypsin treatment of the effectors only inhibited killing of the B16 tumor cell line. Cytotoxicity exerted against YAC-1 remained unaltered upon trypsinization of LAK cells. These cumulative results indicate heterogeneity of both the receptors on the LAK cells and the surface antigen molecules recognized on these targets. The use of YAC-1 as a target provided us with a tool to compare the LAK with the natural killer (NK) systems. The overall effect of proteolytic enzyme treatment in reducing cell lysis was more pronounced in the NK than in the LAK system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Potent graft antitumor effect in natural killer-resistant disseminated tumors by transplantation of interleukin 2-activated syngeneic bone marrow in mice.

The current study is a continuation of our previous work showing that bone marrow activated in interleukin 2 has antitumor and antiviral activity in vitro. The antitumor efficacy of IL-2-activated bone marrow cells in vivo was assessed here. Our results indicated that bone marrow cells activated in IL-2 for 3 days (ABM) have antitumor activity in vivo and cause significant tumor regression in mice being treated with ABM and concurrent i.p. administration of IL-2. In mice also bearing larger tumor burdens, those receiving ABM and i.p. IL-2 showed the most significant tumor regression. The ABM seem to be more potent than conventional IL-2-activated spleen lymphokine-activated killer cells. In studies done using lower dosages of IL-2 or log lower number of cells, the ABM caused more significant tumor regression than lymphokine-activated killer cells. We also assessed the antitumor efficacy of short term (1 day) IL-2-activated bone marrow, the short term-activated bone marrow being preferred in bone marrow, transplantation because of the minimum amount of cells lost due to its shorter incubation period. We also showed that short term-activated bone marrow caused tumor regression similar to ABM and could reconstitute lethally irradiated mice similar to fresh bone marrow. Therefore, the biomodulation of bone marrow cells could be used as an active therapeutic tool in autologous bone marrow transplantation, producing graft versus tumor effects without any graft versus host effect.

Animals↗
PubMed1989

Class A drug users: prevalence and characteristics in greater Nottingham.

This paper reports on the prevalence of known Class A drug use in Greater Nottingham, a large urbanized area with a population of 472,285 in 1981. Use of a multi-agency enumeration technique identified only 170 users during 1985-86, giving an annual prevalence of 0.45 per 1000 of the adult population. The rates for opioid use and injected amphetamine use were 0.27 and 0.14 per 1000. Geographical analysis of the intra-urban residential distributions of the drug users identified statistically significant variations with the greatest concentrations occurring in the inner city residential areas, in neighbourhoods fringing major suburban shopping centres, and several council estates. Ecological analysis established statistically significant links between drug use and multiple deprivation, adult unemployment and crime.

Adolescent↗
PubMed1988

Therapy of disseminated NK-resistant tumor by the synergistic effects of recombinant interleukin-2 and tumor necrosis factor.

Tumor necrosis factor and interleukin-2 each in recombinant form have antitumor activity against established tumors if used in high enough dosages. The problem associated with such high dosages is the high degree of toxicity and expense encountered. Therefore, this study was undertaken to look at the antitumor efficacy of these two lymphokines when used together at dosages well below the toxic levels. Our results using recombinant human interleukin-2 (IL-2) and recombinant human tumor necrosis factor (TNF) against established methylcholanthrene-induced fibrosarcoma (MCA sarcoma) pulmonary metastases showed that TNF and IL-2 therapy at low nontoxic dosages alone did not produce significant tumor regression, but when combined at the same dosage synergize producing significant antitumor effects in mice induced with MCA sarcoma. This was also evident from histopathological examination of the lungs where the maximum tumor reduction along with the maximum lymphocytic infiltration into tumor was seen when TNF and IL-2 were combined. In this tumor regression, inherent immunity of the treated mice was needed, since in those mice in which we induced immunosuppression by using radiation, tumor regression was not seen when TNF and IL-2 therapy was combined in the doses efficacious in immunocompetent mice. Tumor regression is also dependent on the sequence of administration of IL-2 and TNF, since when IL-2 was administered before TNF, the tumor regression was more significant than when TNF was administered before IL-2 or when both were administered simultaneously to mice with established pulmonary tumors. Therefore the synergistic effect of IL-2 and TNF could be used as an efficacious but inexpensive and nontoxic alternative to therapy with lymphokine activated killer (LAK) cells + IL-2.

Animals↗
PubMed1982

Delayed hypersensitivity testing for the prediction of postoperative complications.

One hundred and sixty-six patients undergoing elective major laparotomy were skin tested preoperatively with four common recall antigens in an attempt to correlate preoperative cell-mediated immune status with postoperative septic complications. Nineteen patients were anergic, 22 relatively anergic and the remaining 125 reacted to two or more of the antigens and were regarded as normally reactive. No significant differences in morbidity or mortality were found between patients who had depressed delayed cutaneous hypersensitivity reactions and those who reacted normally. We conclude that identification of those patients with depressed cell-mediated immunity preoperatively does not help in predicting postoperative problems.

Adult↗
PubMed1982

Anaesthesia and intra-ocular pressure: a comparative of total intravenous anaesthesia using etomidate with conventional inhalation anaesthesia.

Intra-ocular pressure (IOP) was measured in two comparable groups of anaesthetised patients under standardised conditions. Group 1 received etomidate 0.3 mg/kg fentanyl 100 micrograms and droperidol 5 mg. with etomidate 20 microgram/kg/minute for maintenance. Group 2 received thiopentone 3.5 mg/kg and were maintained with halothane 0.5% in nitrous oxide (60%) with oxygen. Both groups of patients were ventilated to normocapnia. Blood pressure, heart rate, central venous pressure and IOP were measured in 5 minute intervals from pre-induction to 30 minutes postinduction. A significantly greater reduction in mean IOP (p less than 0.05) occurred in group 1. A maximum fall in IOP of 61% was obtained, compared to a maximum fall of 45% in group 2. Blood pressure fell in both groups. The fall was greater (23%) in group 2 than in group 1 (18%) and in no case was considered excessive. Total intravenous anaesthesia using etomidate is suggested as a useful technique for open eye surgery.

Adult↗
PubMed1979

Psychiatrists' assessments of mental illness. A comparison of some aspects of Thomas Scheff's approach to labelling theory.

The labelling theory of mental illness and particularly that version formulated by Thomas Scheff has been applied to psychiatry. Studies completed by Scheff have produced considerable evidence to support labelling theory. An attempt is made here to determine to what extent labelling theory applies to a group of British psychiatrists. The results give little support to Scheff's position.

Attitude of Health Personnel↗