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Biomedical subjects

M King

Publications and source records attributed to M King.

At least 325 records · Page 18Linked to original sources

Leukocyte inhibitory factor stimulates neutrophil-endothelial cell adhesion.

We investigated the ability of the human lymphokine leukocyte inhibitory factor (LIF) to modulate neutrophil-endothelial cell (EC) adherence. EC were cultured from collagenase-treated human umbilical cord veins and grown in complete medium supplemented with EC growth factor. Adherence was measured as the percent of 51Cr-labeled neutrophils remaining adherent to the EC after gentle lavage. Polymorphonuclear neutrophils (PMN) were pretreated with LIF (0.5 to 8 U/ml), extensively washed, and allowed to interact with the EC monolayers. LIF was demonstrated to induce an increase in the capacity of PMN to bind EC in a dose-dependent fashion (from 30.9 +/- 2.1% adherence with control-treated PMN to 68.6 +/- 3.0% at 4 U LIF; p less than 0.001). In subsequent experiments we demonstrated that 10 min was a sufficient preincubation time for LIF to modulate the capacity of the PMN to adhere to EC. LIF has previously been observed to up-regulate expression of C receptor type 3 on PMN, a receptor which has been shown to be involved in PMN-EC binding. Exposure of PMN to anti-C receptor type 3 antibody before their incubation with LIF abrogated its effect as did inactivation of LIF by an esterase inhibitor. We also investigated the ability of LIF to stimulate EC to bind untreated PMN. EC were pretreated with LIF (0.25 to 4 U/ml), extensively washed, and adherence measured as before. LIF was shown to induce a dose-dependent increase in the capacity of the EC to bind PMN (from 28.8 +/- 3.1% for untreated EC to 91.1 +/- 4.0% at 4 U LIF; p less than 0.001). Modulation of EC function required a minimum of 30 min and was inhibited in the presence of cycloheximide or actinomycin D. Neither anti-TNF-alpha or -beta antibodies nor polymixin B abrogated the augmentation by LIF. However, anti-IL-1 antibody partially inhibited the stimulation of EC adhesiveness by LIF, suggesting the possible involvement of this cytokine. These studies provide further evidence that LIF may mediate an important pro-inflammatory role in vivo.

Cell Adhesion↗

Effect of endogenous and synthetic sex steroids on the clearance of antibody-coated cells.

Steroid hormones may influence the clinical expression of immunologic disease; however, their mechanism of action is uncertain. By using an experimental model, we studied the effect of sex steroids on the clearance of antibody-coated cells by macrophages in the spleen and liver. Progesterone significantly inhibited the clearance of IgG-coated E by splenic macrophages, whereas no effect was observed on the clearance of heat-altered E. This effect of progesterone was observed at serum concentrations which are attained during human pregnancy and the menstrual cycle. Furthermore, when splenic macrophages were isolated from progesterone-treated animals, they expressed decreased Fc gamma R activity. In addition, structural analogs of progesterone which have diminished glucocorticoid and progesterone activity retained this effect on macrophage Fc gamma R. In contrast, the estrogens estradiol and estriol as well as a structural estrogen analog with minimal estrogenic activity, 1,3,5(10)-estratrien-3,16 beta-diol, enhanced splenic macrophage Fc gamma R-dependent clearance. This action of estradiol could be partially inhibited by the antiestrogen tamoxifen. However, estradiol did not affect the C3-dependent clearance of IgM-coated E by hepatic macrophages. Concurrent administration of estradiol and progesterone demonstrated that the action of estradiol was predominant. These studies indicate that sex steroids alter splenic macrophage Fc gamma R function in vivo. This result may explain the alteration of disease activity in some human immunologic disorders during changes in hormonal state. Furthermore, analogs of progesterone and estrogen, as well as antiestrogens, which minimally affect the sex organs, retain the ability to alter splenic macrophage Fc gamma R function.

Animals↗

A phase I-II study of ifosfamide in combination with adriamycin in the treatment of adult soft tissue sarcoma.

Fifty-four patients with advanced soft tissue sarcoma were treated with a combination of ifosfamide (5 g/m2) and adriamycin (40-60 mg/m2) at 3 weekly intervals. Of the 50 evaluable patients a response was seen in 11 (22%) patients (3 complete and 8 partial responses), stabilization of disease occurred in 17 patients and the remaining 22 patients progressed whilst on treatment. Of the 22 patients receiving adriamycin 60 mg/m2 12 (55%) required a dose reduction due to toxicity compared to 11 (39%) of the 28 patients who received 40 mg/m2. For the patients who had a response the median relapse-free interval was 7 months (range 2-17+) and the overall median survival was 12 months (range 5-29+). The combination does not appear to show an advantage over either drug used as a single agent.

Adolescent↗

Mucus transport by high-frequency nonsymmetrical oscillatory airflow.

To study air-mucus interaction as a possible mechanism of tracheal mucus transport and to test the validity of using surface tracer displacement to indicate bulk mucus transport, we performed a combined experimental-theoretical study. We hypothesized that the mucus mass is moved by the difference between expiratory and inspiratory velocities. The rate of transport of a layer of simulated mucus lining the bottom of a rectangular trough was measured in two ways during oscillatory air flow. Peak velocity ratios (R) from 1.0 to 2.0, frequencies (f) between 7 and 13 Hz, and tidal volumes (VT) between 50 and 100 ml were generated by a custom-made pump. The experimental results demonstrate that measuring the displacement of a tracer deposited on the surface of the mucus layer is equivalent to measuring bulk mucus movement by weight. Moreover the measured mucus velocities (micron) correlate well with a theoretical model which predicts that micron is proportional to delta VT f1.5 (R-1). These results suggest that shearing at the air-mucus interface could be a significant factor in the enhanced tracheal mucus clearance during high-frequency chest wall oscillation.

Animals↗

Sampling technique and rheology of human tracheobronchial mucus.

The aims of this work were: (1) to establish a technique for the sampling of human tracheobronchial mucus not contaminated by saliva or topical anesthesia, and (2) to measure its viscoelastic properties. After local anesthesia of the hypopharynx by topical application of 4% xylocaine, a double-sleeve microbiology specimen brush was introduced into a flexible bronchoscope placed in the trachea. The brush was left in direct contact with the bronchial mucosa for 20 to 30 s to allow mucus to collect on it. The mucus sample was then scraped from the brush and immediately covered with paraffin oil. Its viscoelastic properties were determined by the magnetic microrheometer technique. Excluding the time to anesthetize, the whole procedure took less than 1 min (thus minimizing the effect of cough) and resulted in sufficient mucus for rheologic analysis in approximately 90% of trials, i.e., 2.1 +/- 1.5 (SD) mg. Mucus specimens were collected from 20 fasting healthy nonsmoking subjects; 17 of them returned for a second collection several days later. Values for mucus mechanical impedance (vector sum of elasticity and viscosity) at 1 rad/s were: Control 1, 141 +/- 41 (SE); Control 2, 155 +/- 58 dyn/cm2. There was a large variation in mucus viscoelasticity, both between subjects (CV, 130%) and within the same subject (CV, 55%) on different days. In 7 subjects, mucus samples were collected 15 min after intravenous injection of 0.6 mg atropine. Viscoelasticity in these samples was 708 +/- 147 dyn/cm2, a value significantly different from Control 1 (p less than 0.05) and Control 2 (p less than 0.05) values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Managing the difficult patient: practical suggestions from a study day.

A study day for general practitioners was arranged on the subject of managing the difficult patient. Participants were asked to supply written details of their most difficult patient and the problems they associated with him or her. The issues raised were addressed in a number of formal presentations and formed the basis for discussion in workshops. This paper focuses on the underlying similarities between the patients and discusses a practical approach to their management.

Adolescent↗

In vivo red blood cell compatibility testing using indium-113m tropolone-labeled red blood cells.

In vivo radionuclide crossmatch is a method for identifying compatible blood for transfusion when allo- or autoantibodies preclude the use of conventional crossmatching techniques. A technique for labeling small volumes of donor red blood cells with [113mIn]tropolone is reported. The use of 113mIn minimizes the accumulation of background radioactivity and the radiation dose especially so when multiple crossmatches are performed. Labeling red cells with [113mIn]tropolone is faster and easier to perform than with other radionuclides. Consistently high labeling efficiencies are obtained and minimal 113mIn activity elutes from the labeled red blood cells. A case study involving 22 crossmatches is presented to demonstrate the technique. The radiation dose equivalent from 113mIn is significantly less than with other radionuclides that may be used to label red cells.

Adult↗

Methanol fixation permits flow cytometric analysis of immunofluorescent stained intracellular antigens.

Fixation and immunofluorescent staining methods were developed for analyzing intracellular antigens with the cell flow cytometer. Fixing cell suspensions with 100% methanol provided best preservation of morphology, lowest fluorescent background staining and most intense specific immunofluorescence. Immunoglobulins present in B cell lines that were representative of different developmental stages could be distinguished quantitatively. Fluorescence histograms were compared with fluorescence microscope presentation of stained cells. Intracellular antigens that reacted with monoclonal antibodies could also be evaluated by flow cytometry. This method was utilized to assess plasmacyte development in mouse spleen cell cultures after stimulation with lipopolysaccharide.

Animals↗

The "epidemic" of anorexia nervosa: another medical myth?

Examination of data on patients admitted to psychiatric facilities in England in 1972-81, inclusive, with a main diagnosis of anorexia nervosa showed that first admissions for women rose significantly with time--age-period-cohort analysis showed that this was due entirely to an increase in the number of young women in the population rather than to an increase in risk of morbidity. There were significant increases with time in the readmission rates for both sexes. For the women, these were due to a complex interrelation between age, period, and cohort effects. This rising readmission rate may have contributed to the widely held impression that the incidence of anorexia nervosa has risen sharply.

Adolescent↗

Textile arterial prostheses: is water permeability equivalent to porosity?

Porosity and water permeability are two distinct terms that describe different characteristics of vascular prostheses. The porosity is a measure of the void fraction within the prosthesis wall and is believed to give a rough prediction of the capacity of the graft to anchor newly formed surrounding tissue after implantation, whereas the water permeability indicates the rate at which water can flow through the prosthesis wall and, when measured under physiological pressure conditions, provides the surgeon with information about the need for preclotting prior to implantation. The literature has not always clearly distinguished between these two terms, and some authors in fact have suggested that they both refer to the same property of a prosthesis. In an attempt to clarify the issue, porosity and water permeability measurements were made on 34 commercial vascular prostheses having different textile constructions. Linear regression analysis demonstrated that these two characteristics are only weakly related (r = 0.59). It is therefore recommended that the current draft standards for such devices reference both properties: porosity and water permeability.

Blood Vessel Prosthesis↗