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Biomedical subjects

J O'Brien

Publications and source records attributed to J O'Brien.

At least 199 records · Page 11Linked to original sources

Clinical use of dreams with latency-age children.

Although various authors have discussed the technical modification required for dream interpretation with children, the basic conceptualization of the psychotherapeutic use of the dream with children has remained virtually identical to that with adult analysands. Examining various sources including formal studies on the nature of children's dreams, clinical case reports and series, and cognitive theories, the authors conclude that a dream arising in the course of a child's therapy must be conceptualized theoretically as a posttraumatic phenomenon. This holds whether or not there has been overt trauma to the child. The reasons for the conceptualization include both the heightened degree of anxiety contained in a dream reported in the course of psychotherapy as well as the specific cognitive abilities of children to contain anxiety and abstract and generalize symbolic meanings. A specific technique based on this conceptualization is then detailed that calls for translation of the dream into more tangible expression (drawing, play, etc.) and a noninterpretative approach. The authors also discuss the more general problem of the nature of insight in children.

Child↗

Life events: the reliability of rating changes in routine and environment.

Alterations in routine and environment can affect clinical state in patients suffering from cognitive impairment. A method for rating life events for changes in routine and environment is described and found to be highly reliable even when used by inexperienced raters after brief training.

Activities of Daily Living↗

Amino acid receptors from insect muscle: electrophysiological characterization in Xenopus oocytes following expression by injection of mRNA.

Poly(A)+ Messenger ribonucleic acid (mRNA) was extracted from leg muscles of the locust Schistocerca gregaria and injected into oocytes of Xenopus laevis. After 5-10 days incubation, receptors for L-glutamate, L-quisqualate, DL-ibotenate and gamma-aminobutyric acid (GABA) were expressed. Agonist-induced currents were dose-dependent, and, in the concentration range 1 microM to 1 mM, generally had peak values of 50 nA. The responses to all agonists, apart from GABA, exhibited desensitization which could not be reversed even by prolonged washing with Ringer. Application of 100 microM GABA to oocytes voltage clamped at -60 mV produced a smooth inward current with a reversal potential of -22 +/- 1 mV, which is consistent with the involvement of chloride ions. At 100 microM, picrotoxin reversibly abolished this current, while 100 microM bicuculline had no effect. L-Glutamate elicited a smooth current with a reversal potential of -52 +/- 3 mV. L-Quisqualate elicited an inward current at -60 mV with a reversal potential of -9 +/- 2 mV; this current occasionally had an oscillatory component. The response to ibotenate comprised a smooth inward current with a reversal potential of -21 +/- 3 mV which was probably mediated by chloride ions.

Amino Acids↗

Production of thiosulphate during sulphide oxidation by mitochondria of the symbiont-containing bivalve Solemya reidi.

Isolated mitochondria of the bivalve Solemya reidi Bernard oxidize sulphide and couple this oxidation to ADP phosphorylation. The products of mitochondrial sulphide oxidation were analyzed by HPLC using monobromobimane derivatization. Concurrent measurements of respiration were made using sulphide-insensitive oxygen electrodes. S. reidi mitochondria oxidized sulphide exclusively to thiosulphate. The reaction occurred in two steps. One sulphide molecule was first oxidized to sulphite. A second molecule of sulphide was then added oxidatively to form the free product thiosulphate. This oxidation was obligately linked to mitochondrial electron transport and could be inhibited by the cytochrome c oxidase inhibitor hydrogen cyanide, or by low oxygen concentration. The site II inhibitor antimycin A did not inhibit thiosulphate production, indicating that sulphide oxidation is linked through only one ATP coupling site (site III). A calculation of the respiratory potential for ATP synthesis by fully intact mitochondria indicated that 2.0-3.25 ATP per sulphide may be synthesized using the proton potential generated by sulphide oxidation. This estimate far exceeds the published phosphorylation ratios for S. reidi (0.5-1.2 ATP per sulphide). This difference may be accounted for by partial uncoupling of phosphorylation from sulphide-based respiration. This hypothesis is supported by the observation that the respiratory control ratio of mitochondria respiring on sulphide is 41% lower than that of mitochondria respiring on succinate. The respiratory control ratio is an index of the tightness of coupling of respiration to ADP phosphorylation. When the adenylate pool of a eukaryotic cell is mostly phosphorylated, respiration is very slow, owing to the maintenance of a high mitochondrial membrane potential. Uncoupling of oxidative phosphorylation from respiration would be an adaptive advantage to the animal in that it allows for continuous, rapid removal of the toxic molecule hydrogen sulphide.

Adenosine Triphosphate↗

Differences in affinity of anti-CD4 monoclonal antibodies predict their effects on syncytium induction by human immunodeficiency virus.

A panel of 20 anti-CD4 monoclonal antibodies (mAb) was ranked in terms of affinity, using an inhibition radioimmunoassay. The ability of these antibodies to inhibit the induction of syncytia by human immunodeficiency virus (HIV) and to prevent binding of the HIV envelope glycoprotein 120 (gp120) to CD4 was also measured. Syncytium inhibition correlated strongly with affinity (P less than 0.001) but only weakly with inhibition of gp120 binding (P = 0.038). Some antibodies partially blocked binding of gp120 to CD4 but did not inhibit syncytia, and some antibodies inhibited syncytia but only weakly blocked binding of gp120. These results suggest that the syncytium inhibition assay is highly affinity-dependent, and that epitopes on CD4 concerned with virus binding are distinct from those involved in syncytium formation.

Antibodies, Monoclonal↗

Seasonal affective disorder.

Depression during winter has been found to respond to treatment with simulated daylight. Seasonal affective disorder should be distinguished from other forms of depression which can also occur in winter before prescribing light therapy.

Diagnosis, Differential↗

Evidence for distinguishable transcripts of the putative testis determining gene (ZFY) and mapping of homologous cDNA sequences to chromosomes X,Y and 9.

Oligonucleotide sequences based on the amino acid sequence of the putative testis determining gene ZFY have been used to isolate a 1.3 Kb Hind III Y genomic DNA fragment CMPXY1 and three human testis cDNA sequences (CMPXY2, CMPXY3 and CMPXY4). These sequences detect at least four potential exons on the Y (Y1, Y3, Y4 and Y5), three on the X (X1, X2 and X3) and three of autosomal origin (A1, A2 and A3) as determined by comparing the fragments detected by different clones. Analysis with subfragments of CMPXY4 shows that Y3 is unique to the Y and that Y4 and X1 are homologous. Y5 and X3 are detected by the same subfragment of CMPXY4. This is also the case for Y1, X2, A1, A2 and A3. Thus these exons may contain further regions of homology between the X, Y and an autosomal locus. The X-linked sequences all lie in Xp21.2-Xp22.1 and studies with XX males have placed the Y-linked sequences in distal Yp adjacent to the Y-autosomal homologous sequence GMGY3. We have confirmed these localizations by in situ hybridization with CMPXY4 and have shown additionally that the autosomal sequences of both the CMPXY4 sequence and GMGY3 map to 9p22-9pter. Restriction analysis demonstrates that CMPXY1/XY2/XY3 differ in sequence from CMPXY4 at three restriction enzyme sites, thus suggesting that they are transcribed from different but closely related genes and that CMPXY4 must be either X-linked or autosomal in origin. This indicates that more than one of the loci containing ZFY-related sequences are transcribed and potentially fulfil functionally distinct roles in the human sex determining pathway. Northern blot analysis of human foetal testis RNA has shown that three low abundance transcripts of 5, 6 and 8 Kb can be detected by ZFY-related DNA sequences.

Base Sequence↗

Cigarette smoke degrades hyaluronic acid.

Cigarette smoke has been implicated in the pathogenesis of a variety of diseases that affect connective tissues. The effect of the gas phase of cigarette smoke on hyaluronic acid was investigated in vitro. The smoke markedly reduced the chain length of purified hyaluronic acid as assessed by both viscometry and gel chromatography. The hyaluronate exposed to smoke, nevertheless, could aggregate proteoglycans, although the viscosity of the aggregates was lower than in those formed with the unexposed material. The degradation of the hyaluronate was a rapid phenomenon and was inhibited by dimethylsulfoxide, a known scavenger of hydroxyl radicals. We conclude that free radicals in the gas phase of cigarette smoke degrade hyaluronic acid in vitro.

Chromatography, Gel↗

Nutritional and toxicological aspects of the Maillard browning reaction in foods.

The Maillard, or nonenzymatic, browning reaction between carbonyl and amino groups is a common reaction in foods which undergo thermal processing. The Maillard reaction is a desirable consequence of many industrial and domestic processes and is responsible for the attractive flavor and brown color of some cooked foods. An early recognized consequence of the Maillard reaction was the destruction of some essential amino acids, such as lysine. More recently, research interest has focused on the production of toxic and antinutritive compounds. This review examines the nutritional and toxicological consequences of the Maillard reaction in light of the findings of such research. In particular, the effect of Maillard reaction products on the digestion, absorption, and excretion of nutrients is considered. The cytotoxicity, mutagenicity, and immunochemical aspects of selected Maillard reaction products are also examined and suggestions are made for future areas of investigation.

Allergens↗

Effector characteristics of the IgG3 murine monoclonal antibody 113F1.

Successful immunotherapy with unconjugated murine monoclonal antibodies (MAbs) is likely to require antibodies with potent effector characteristics such as antibody-dependent cellular cytotoxicity (ADCC). The newly developed IgG3 isotype antibody, 113F1, binds to a target antigen present in high copy number on SK-Br-3 cell surfaces. 113F1 does not appear to participate in complement-mediated cytotoxicity, but is a potent mediator of ADCC by human monocytes directed against a variety of malignant cell lines expressing 113F1's target antigen. Although recombinant interleukin-2 (rIL-2) promotes nonspecific monocyte cytotoxicity, preincubation with this cytokine has no effect on monocyte ADCC in our system. 113F1 promotes ADCC by nonadherent cells expressing lymphokine-activated killer (LAK) activity following incubation of these cells in rIL-2. These latter effects are abrogated by Fc receptor blockade prior to addition of 113F1. 113F1 is a more potent mediator of ADCC by monocytes or LAK cells than is 17-1A, an extensively tested unconjugated murine IgG2a isotope MAb. These data suggest that unconjugated 113F1 MAb immunotherapy trials should investigate treatment with the MAb alone. In addition, 113F1 could be administered with rIL-2, either alone or supplemented with infusions of autologous LAK cells.

Animals↗

Antibody delivery and effector cell activation in a phase II trial of recombinant gamma-interferon and the murine monoclonal antibody CO17-1A in advanced colorectal carcinoma.

Murine monoclonal antibodies of the immunoglobulin G2a isotype interact with human effector cells to mediate antibody-dependent cellular cytotoxicity (ADCC) directed against malignant cells which express antigens recognized by these antibodies. gamma-Interferon enhances these effects in vitro. In a Phase I trial of murine monoclonal antibody CO17-1A and recombinant gamma-interferon (rIFN-gamma), we demonstrated that low doses of rIFN-gamma were superior to high doses in augmenting ADCC mediated by treated patients' monocytes. These results formed the basis for a Phase II trial of CO17-1A combined with low dose rIFN-gamma. Nineteen patients with metastatic colorectal carcinoma were treated with four consecutive daily infusions of 1.0 X 10(6) IU/m2 rIFN-gamma, with 150 mg of CO17-1A administered on days 2, 3, and 4. Therapy was tolerated well. Peripheral blood mononuclear cells were purified from patient samples obtained at baseline and at 1, 4, or 24 h following the start of the first rIFN-gamma infusion and were tested for their ability to lyse 111In-labeled cells of the SW1116 colorectal line. Enhancement of monocyte ADCC was seen by 24 h, while lymphocyte ADCC and natural killer activity directed against K562 cells were enhanced to a lesser extent. Nonspecific lysis of SW1116 cells by effectors was not seen at the time points examined. While CO17-1A antigen expression was observed in most biopsies, 131I-labeled CO17-1A imaged positively in less than one-half of the organs known to harbor metastases, and therapeutic antibody delivery was not always demonstrated by immunoperoxidase staining techniques of tissue obtained following therapy. In antigen-positive lesions, tissue pO2 levels appear to identify lesions which would image positively. No objective responses were seen. Our findings suggest that prolonged therapy with low doses of rIFN-gamma potentiates ADCC but that physiological obstacles to therapeutic antibody delivery are significant. In order to evaluate the validity of this therapeutic approach, measures to enhance antibody delivery are needed, starting with systematic evaluations of therapy with escalating doses of CO17-1A combined with low dose rIFN-gamma therapy.

Adult↗

Restriction of blood and marrow CLL-B cells to free L-chain Ig secretion: implication for normal B-cell function and control.

The culture supernatant immunoglobulin (CSIg) of blood mononuclear cells (MNCs) from 14 patients with chronic lymphocytic leukemia (CLL) was determined using a panel of nanogram-sensitive radioimmunoassays that measured IgM, IgG, IgA, total kappa-Ig, and total lambda-Ig. Bone marrow cells from three patients were also cultured and the blood and marrow CSIg results were compared. The CSIg of 1-day cultures was employed as a measure of shed surface membrane Ig (SmIg) for the 7- and 14-day cultures. Adjusting for shed SmIg, it was found that in resting unstimulated conditions, monotypic free light (L) chain was virtually the only identifiable secreted Ig product in 12 of 14 blood MNC cultures and in three of three marrow cell cultures. In pokeweed mitogen (PWM)-stimulated cultures, monotypic free L chain also dominated, except for significant polyclonal Ig secretion found in three cultures from residual normal blood MNCs. The secretion by CLL-B cells of significant amounts of free L chain with a virtual absence of whole Ig raises important questions about the presence and function of phenotypically equivalent normal B cells in blood and bone marrow, and also the immunological role of secreted free L chain. Noting recent evidence that PWM-stimulated normal blood MNCs secrete significant amounts of polyclonal free L chain, the argument is advanced that normal blood and bone marrow contain B cells of CLL-B phenotype and that secreted free L-chain-bearing clonal idiotypic markers interact with autologous cells of the idiotypic regulatory network and possess a key role in the regulation of clonal growth and Ig synthesis.

Aged↗

Toxicological effects of dietary Maillard reaction products in the rat.

The effects of dietary glutamate/glucose Maillard reaction products (MRP) on the rat were studied. Rats fed 5 and 10% MRP developed severe diarrhoea that persisted throughout the 5-wk feeding study. An increase in water consumption by these animals was attributed to excessive faecal water losses due to diarrhoea. Body weights were significantly depressed in animals fed 10% MRP compared with rats fed a control isocaloric diet or a diet containing 10% of an unreacted mixture of glutamate/glucose. MRP ingestion also resulted in a dose-related caecal enlargement, which was accompanied by a decrease in the osmolality of caecal contents, compared with control values. Relative kidney and liver weights were significantly increased in rats fed 10% MRP. Despite a high background incidence of cortico-medullary nephrocalcinosis in all groups in the study reported here, the condition was significantly more pronounced in rats fed MRP, as assessed by mineral analysis and histological examination. In addition, bladder urothelial thickness was significantly greater in rats fed either level of MRP compared with values for control animals. Finally, caecal goblet cell density was significantly reduced in rats fed MRP compared with counts for control animals.

Animals↗

A genetic marker for systemic amyloidosis in juvenile arthritis.

A genetic marker of susceptibility to systemic amyloidosis has been identified. A DNA polymorphic site, 5' to the serum amyloid P component gene, has been found to be significantly associated with amyloidosis in juvenile arthritic patients. When genomic DNA was cut with the restriction enzyme MspI and probed with the cDNA for serum amyloid P component, homozygosity for the 5.6 kb restriction fragment length polymorphic (RFLP) band was absent in all 28 amyloid patients. Furthermore, the proportion who were homozygous for the 8.8 kb RFLP band was greater (p = 0.008) than that among 89 normal subjects. The distribution of this polymorphic site among 19 juvenile arthritic patients without amyloidosis was the same as that in the normal group. Thus the 8.8 kb RFLP band represents a genetic predisposition to reactive amyloidosis in juvenile arthritis and may apply to amyloidosis associated with more common inflammatory conditions.

Adult↗

Evaluation of the efficacy and acceptability to patients of a physiotherapist working in a health centre.

The records of the first 805 patients who had been referred by general practitioners at this health centre to the attached physiotherapist were examined in November 1985, three years after the physiotherapy department was opened. Seventy per cent (549) of the patients had been treated within one week, treatment having started on the same day for 8.5% (67) of the patients. This compares with a mean of six weeks for direct access to a district general hospital that is eight miles away and between six and 13 months for the three nearest orthopaedic consultants who are 13 miles away. The most common conditions treated were knee injuries (16.5%), followed by cervical (15.5%) and shoulder (13.8%) injuries. Surprisingly, only 9% were back injuries. The non-attendance rate was 2.2% and only 7% of patients failed to complete treatment. Nearly all the patients were able to attend the clinic, only 4% requiring home treatment. By March 1986, 90 treatments a week were being carried out at a cost of 6.11 pounds per patient. Compared with official hospital figures, this represents a savings of 21,500 pounds a year for a practice of 12,000 patients.

Adolescent↗