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Biomedical subjects

J O'Brien

Publications and source records attributed to J O'Brien.

At least 217 records · Page 12Linked to original sources
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Management of end stage respiratory failure in Duchenne muscular dystrophy.

There were 31 Duchenne patients placed on overnight mouth intermittent positive pressure ventilation for severe respiratory insufficiency at the average age of 19.9 years. Most patients had vital capacities less than 200 cc at their last evaluations. Of these, 23 patients are alive at the average age of 27 years and live in the community, although they are dependent on assisted ventilation 24 hours a day. There were 8 patients who died at the average age of 30 years. Although normocapnic during the day, the presence of symptomatic nocturnal hypoventilation or pCO2 over 55 mmHg documented by continuous overnight capnograph study indicates the need for introducing overnight respiratory assistance. Mouth intermittent positive pressure ventilation alone or in combination with other techniques of ventilatory assistance can prolong life while allowing optimal function, attainment of higher levels of education, and home management of patients with Duchenne muscular dystrophy.

Adolescent↗
PubMed1986

Sensitivity of veiled (dendritic) cells to cyclosporine.

The effect of cyclosporine (CsA) on dendritic cell function was tested by pulsing rabbit veiled cells (VC, the "dendritic" cells from the afferent lymph) with the drug. This treatment inhibited their capacity to enhance proliferative responses of autologous peripheral blood lymphocytes to the mitogen concanavalin A. The concentration of CsA required to produce inhibition varied from one rabbit to another and ranged from 5 to 100 ng/ml. The degree of inhibition was greater under conditions in which the normal VC were more effective. Addition of further untreated VC restored the response, but this restoration was incomplete under some culture conditions. Pulsing peripheral blood mononuclear cells (PBM) with CsA also produced a reduction in the stimulation by Con A, and the response was not restored by addition of normal VC. The experiments did not distinguish whether the effect of CsA was directly on dendritic cell function or via a secondary effect of "presentation" of CsA to lymphocytes by the dendritic cells.

Animals↗