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Biomedical subjects

J Storm

Publications and source records attributed to J Storm.

15 recordsLinked to original sources

Is episialin/MUC1 involved in breast cancer progression?

Episialin, also designated MUC1, CA 15-3 antigen and PEM, is an established serum marker for breast cancer. Its function and possible involvement in tumor progression has not yet been completely established. The molecule is an extended rod-like molecule protruding high above the cell surface. It is often highly overexpressed in breast cancer relative to normal breast epithelium cells. Overexpression of episialin on cells in vitro reduces cell-cell and cell-extracellular matrix adhesion, because the rod-like molecule masks the adhesion receptors. Episialin also exerts its anti-adhesion effect in vivo. In certain human tumors, where episialin was present at the basal side of the cell, abnormal contacts between the plasma membrane and the stroma were observed. As a consequence of its anti-adhesion properties, episialin overexpression reduces the sensitivity of the cells for cytotoxic lymphocytes. This might be one of the reasons why episialin transfected cells are more potent to form experimental metastases after i.v. injection into nude mice.

Animals

Radioimmunotherapy of small-cell lung cancer xenografts using 131I-labelled anti-NCAM monoclonal antibody 123C3.

We have studied the therapeutic efficacy of 131I-labelled monoclonal antibody 123C3 in human small-cell lung carcinoma xenografts established from the NCI-H69 cell line in nude mice. Several radiation doses were administered intraperitoneally and different treatment schedules were tested. The maximal tolerated dose, 2 x 500 microCi, resulted in complete remission of tumours smaller than 200 mm3 and long-lasting remission (more than 135 days) of the larger tumours. In control experiments, treatment with unlabelled monoclonal antibody 123C3 did not affect the tumour growth rate, while the effect of radiolabelled non-relevant, isotype-matched, monoclonal antibody M6/1 was minor and transient. Regrowth of the tumours occurred in all cases and could not be attributed to loss of neural cell adhesion molecule (NCAM) expression. Tumour recurrence is probably caused by insufficient radiation dosage. Radiation-induced toxicity was monitored by assessment of weight and bone marrow examination. Weight loss was observed in all treatment groups, but the mice regained their initial weight within 14 days, except for the group receiving the highest radiation dose (3 x 600 microCi). In this group all mice died as a result of radiotoxicity. Of the mice injected with 600 microCi radiolabelled control antibody, 50% died within 2 weeks after administration. Apparently the higher uptake of the radiolabelled monoclonal antibody in the tumour reduced systemic radiation toxicity.

Animals

Binding of surfactant protein A to the lipid A moiety of bacterial lipopolysaccharides.

Surfactant protein A (SP-A) enhances the phagocytosis of opsonized and non-opsonized bacteria by alveolar macrophages, but it is not known with which component of the bacterial surface it associates. We investigated the interaction of SP-A with lipopolysaccharides (LPS), which are important biologically active constituents of the outer membranes of Gram-negative bacteria. Flow cytometry was used to study the binding of fluorescein isothiocyanate-labelled SP-A either to LPS of various chain lengths coupled to magnetic beads or to Gram-negative bacteria. The binding of SP-A to LPS-coated beads was saturable, both time- and concentration-dependent, and required both Ca2+ and Na+. SP-A bound to the lipid A moiety of LPS and to LPS from either the Re-mutant of Salmonella minnesota or the J5-mutant of Escherichia coli. In contrast, it did not bind to O111 LPS of E. coli, suggesting that SP-A binds only to rough LPS. The binding of SP-A to LPS was not affected by mannan and heparin or by deglycosylation of the SP-A, indicating that the carbohydrate-binding domain and the carbohydrate moiety of SP-A are not involved in its interaction with LPS. We also observed saturable and concentration-dependent binding of SP-A to the live J5 mutant of whole E. coli, but not to its O111 mutant. In addition, Re LPS aggregated in the presence of SP-A, Ca2+ and Na+. We conclude that SP-A associates with LPS via the lipid A moiety of rough LPS and may be involved in the anti-bacterial defences of the lung.

Bronchoalveolar Lavage Fluid

Computer-controlled wheelchair ergometer.

A new wheelchair ergometer has been designed in which a combination of realistic simulation of wheelchair propulsion--with adjustable parameters for rolling resistance, air drag, wind speed and slope--and force measurement has been realised. The static solution enables the measurement of physiological and kinesiological parameters. All data from force transducers in seat and backrest, torque transducers in the wheels and force transducers in the wheelframes as well as the acquired speed are sampled in a data-acquisition system. An offline curve processor allows the acquired data to be processed with standard or custom-programmed routines. Preliminary results have been added and are discussed.

Engineering

Thresholds of action potentials evoked by synapses on the dendrites of pyramidal cells in the rat hippocampus in vitro.

1. In this study we have measured the thresholds of action potentials and some properties of e.p.s.p.s (excitatory post-synaptic potentials) produced by activation of distal and proximal dendritic synapses in CA1 pyramidal cells in rat hippocampal slices. 2. Simultaneous intracellular and extracellular electrophysiological recordings were made from pyramidal cells. The two recording electrodes were positioned very close together to provide an accurate measurement of the transmembrane potential by subtraction of the extracellular field from the intracellular potential. 3. Two pairs of stimulating electrodes were placed in the stratum radiatum of area CA1. The proximal and distal afferents were stimulated alternately within a 15 s cycle and at an intensity to produce action potentials in about 50% of the trials. 4. At this stimulus intensity there was a slight difference in the mean 10-90% rise times of the e.p.s.p.s produced by stimulation of proximal and distal afferents. The ratio of the distal: proximal rise time was 1.27. 5. In those trials where the action potential failed there was also a significant difference in the time-to-peak of the e.p.s.p.s evoked from proximal or distal sites. The times-to-peak of the e.p.s.p.s from proximal stimulation were between 1.5 and 3.8 ms, whilst the times-to-peak from distal stimulation were longer (2.1-7.2 ms). 6. In 16/18 cells included in this study the thresholds for action potentials evoked by distal stimulation were significantly lower than those following proximal activation. The mean threshold for distal activation was 12 mV compared with 16 mV for proximal activation. 7. The threshold of action potentials activated by depolarizing current pulses appeared to be close to that for action potentials evoked from proximal synapses. 8. Whilst the shape indices of the e.p.s.p.s were slightly different when comparing transmembrane with conventional intracellular recordings, the thresholds of the action potentials were not affected by this procedure. 9. Possible explanations for the low threshold for action potentials evoked from distal synapses are discussed, including an active dendritic membrane and differences in inhibition.

Action Potentials

Repetitive firing of CA1 hippocampal pyramidal cells elicited by dendritic glutamate: slow prepotentials and burst-pause pattern.

In order to compare responses to dendritic vs. somatic depolarization, CA1 pyramidal cells in rat hippocampal slices were stimulated by iontophoresis of glutamate to sensitive spots in the dendrites, and by somatic current injection. Low intensities of either stimulus elicited slow repetitive firing. Each action potential was preceded by a slow depolarizing prepotential (SPP), lasting 50-300 ms and was followed by fast (3-5 ms) and slow (more than 100 ms) afterhyperpolarizations (AHPs). The SPPs, and AHPs were indistinguishable for the two types of stimuli. In response to strong depolarizations, most cells showed an initial burst of spikes, followed by a pause before the steady discharge. This pattern was elicited by both glutamate and current. The input resistance usually increased 5-20% during subthreshold depolarizations by glutamate or current. In contrast, large doses of glutamate caused a slow decline in the resistance (up to 40%), which was larger than during comparable current-induced discharge, and the response was followed by a longer AHP. It is concluded that both dendritic and somatic depolarization, induced by glutamate and current, respectively, can elicit sustained repetitive firing with SPPs, fast and slow AHPs and burst-pause pattern, thus, increasing the likelihood that these phenomena play a role during natural activation of CA1 cells.

Animals

Current-to-frequency transduction in CA1 hippocampal pyramidal cells: slow prepotentials dominate the primary range firing.

In order to study how hippocampal pyramidal cells transform a steady depolarization into discharges, CA1 pyramids (n = 32) were injected with 1.5 s long pulses of constant depolarizing current. The firing in response to weak currents was in most cells, characterized by low frequency (0.2-5 Hz), slowly increasing depolarizations preceding each action potential (slow prepotentials, SPPs), a long latency (0.2-5 s) to the initial spike and lack of adaptation. The SPPs, which lasted 30-2,000 ms, showed an increasing steepness with increasing current, and seemed to be a major regulating factor for the slow firing. In response to stronger currents the discharge had a high initial frequency (100-350 Hz), followed by adaptation to steady state firing (5-50 Hz). Thirty of 32 cells showed a dip in the frequency (n = 5), or a pause (n = 25) lasting 250-1,000 ms between the initial burst of firing and the steady state. The pause occurred only at intermediate current strengths. Additional spikes to the initial burst seemed to be recruited through the development of depolarizing waves. The initial slope of these waves resembled those of the SPPs. Similar waves occurred at the expected time of occasionally missing spikes during steady state firing. The variability (SD/mean) of the interspike intervals decreased with increasing frequency of firing. The frequency-current (f/I) relation for the steady state firing showed a simple linear or convex shape, and lacked a secondary range. In contrast, the f/I plots for the initial few interspike intervals had both primary, secondary and tertiary ranges, like motoneurones.

Action Potentials

A new x-ray and light field superimposition detector.

A fast and accurate method to determine the alignment of the diagnostic x-ray and light fields was developed. Following the exposure, the boundaries of an x-ray field are determined by a custom-built x-ray field position detector and indicated by light-emitting diodes. The alignment of the supposed and the actual x-ray fields agree (within +/- 2 mm) with the corresponding results of the film-based procedure.

Humans