Jan Huizinga - Academia.edu (original) (raw)

Papers by Jan Huizinga

Frontiers in physiology, 2018

Simultaneous pressure waves (SPWs) in manometry recordings of the human colon have been associate... more Simultaneous pressure waves (SPWs) in manometry recordings of the human colon have been associated with gas expulsion. Our hypothesis was that the SPW might be a critical component of most colonic motor functions, and hence might act as a biomarker for healthy colon motility. To that end, we performed high-resolution colonic manometry (HRCM), for the first time using an 84-sensor (1 cm spaced) water-perfused catheter, in 17 healthy volunteers. Intraluminal pressure patterns were recorded during baseline, proximal and rectal balloon distention, after a meal and following proximal and rectal luminal bisacodyl administration. Quantification was performed using software, based on Image J, developed during this study. Gas expulsion was always associated with SPWs, furthermore, SPWs were associated with water or balloon expulsion. SPWs were prominently emerging at the termination of proximal high amplitude propagating pressure waves (HAPWs); we termed this motor pattern HAPW-SPWs; hence, ...

PAIN Reports

Introduction: Clinical data on cancer-induced bone pain (CIBP) suggest extensive changes in senso... more Introduction: Clinical data on cancer-induced bone pain (CIBP) suggest extensive changes in sensory function. In a previous investigation of an animal model of CIBP, we have observed that changes in intrinsic membrane properties and excitability of dorsal root ganglion (DRG) nociceptive neurons correspond to mechanical allodynia and hyperalgesia. Objectives: To investigate the mechanisms underlying changes in nonnociceptive sensory neurons in this model, we have compared the electrophysiological properties of primary nonnociceptive sensory neurons at ,1 and .2 weeks after CIBP model induction with properties in sham control animals. Methods: Copenhagen rats were injected with 10 6 MAT-LyLu rat prostate cancer cells into the distal femur epiphysis to generate a model of CIBP. After von Frey tactile measurement of mechanical withdrawal thresholds, the animals were prepared for acute electrophysiological recordings of mechanically sensitive neurons in the DRG in vivo. Results: The mechanical withdrawal threshold progressively decreased in CIBP model rats. At ,1 week after model induction, there were no changes observed in nonnociceptive Ab-fiber DRG neurons between CIBP model rats and sham rats. However, at .2 weeks, the Ab-fiber low-threshold mechanoreceptors (LTMs) in CIBP model rats exhibited a slowing of the dynamics of action potential (AP) genesis, including wider AP duration and lower AP amplitude compared with sham rats. Furthermore, enhanced excitability of Ab-fiber LTM neurons was observed as an excitatory discharge in response to intracellular injection of depolarizing current into the soma. Conclusion: After induction of the CIBP model, Ab-fiber LTMs at .2 weeks but not ,1 week had undergone changes in electrophysiological properties. Importantly, changes observed are consistent with observations in models of peripheral neuropathy. Thus, Ab-fiber nonnociceptive primary sensory neurons might be involved in the peripheral sensitization and tumorinduced tactile hypersensitivity in CIBP.

Anatomical record (Hoboken, N.J. : 2007), Jan 16, 2016

Small intestinal muscularis externa macrophages have been associated with interstitial cells of C... more Small intestinal muscularis externa macrophages have been associated with interstitial cells of Cajal. They have been proposed to play various roles in motility disorders and to take part in a microbiota-driven regulation of gastrointestinal motility. Our objective was to understand the reaction of resident macrophages of the musculature to a pro-inflammatory stimulator, lipopolysaccharide (LPS). Mice were injected with LPS or saline and sacrificed after 6 hr. Whole mounts were stained with antibodies toward CD169, ionized calcium-binding adaptor molecule 1 (iba1) (microglial/macrophage marker) and heme oxygenase-1 (HO-1). Cell densities were measured using unbiased stereology. iba1(pos) cells showed an overall higher density than CD169(pos) and HO-1(pos) cells. Most HO-1(pos) and iba1(pos) cells were positive for CD 169 in serosa and at Auerbach's plexus (AP). At the deep muscular plexus, mainly iba1(pos) cells were present, and were mostly CD169(neg) ; a few HO-1(pos) cells we...

Pflügers Archiv - European Journal of Physiology, 1988

Marked differences were observed in the intracellular electrical activities (spontaneous and TEA-... more Marked differences were observed in the intracellular electrical activities (spontaneous and TEA-induced) comparing the submucosal and myenteric plexus surfaces of the circular muscle of the dog colon. Distinct characteristics of the cells at the myenteric plexus surface ...

American journal of physiology. Gastrointestinal and liver physiology, 2001

Slow waves determine frequency and propagation characteristics of contractions in the small intes... more Slow waves determine frequency and propagation characteristics of contractions in the small intestine, yet little is known about mechanisms of slow wave regulation. We propose a role for intracellular Ca(2+), inositol 1,4,5,-trisphosphate (IP(3))-sensitive Ca(2+) release, and sarcoplasmic reticulum (SR) Ca(2+) content in the regulation of slow wave frequency because 1) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a cytosolic Ca(2+) chelator, reduced the frequency or abolished the slow waves; 2) thapsigargin and cyclopiazonic acid (CPA), inhibitors of SR Ca(2+)-ATPase, decreased slow wave frequency; 3) xestospongin C, a reversible, membrane-permeable blocker of IP(3)-induced Ca(2+) release, abolished slow wave activity; 4) caffeine and phospholipase C inhibitors (U-73122, neomycin, and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate) inhibited slow wave frequency; 5) in the presence of CPA or thapsigargin, stimulation of IP(3) synthesis with carbachol, norepinep...

The Journal of physiology, 1993

1. Electrical communication between circular muscle, longitudinal muscle and interstitial cells o... more 1. Electrical communication between circular muscle, longitudinal muscle and interstitial cells of Cajal (ICC) was investigated; the hypothesis was tested that the resting membrane potential (RMP) gradient in the circular muscle of canine colon is caused by electrical coupling to neighbouring cells. 2. Isolated longitudinal muscle exhibited spike-like action potentials at a RMP of -45 mV with a frequency and amplitude of 20 cycles/min and 12 mV, respectively. 3. The circular muscle (CM), devoid of longitudinal muscle, myenteric plexus and submuscular ICC-smooth-muscle network, was electrically quiescent at a uniform RMP of -62 mV across the entire circular muscle layer. 4. Preparations consisting of only the submuscular ICC network and a few adjacent layers of circular muscle cells exhibited slow wave-type action potentials at a RMP of about -80 mV. 5. In ICC-CM preparations, consisting of the submuscular ICC network and circular muscle, a RMP gradient of 10 mV was observed near the...

The American journal of physiology, 1989

Smooth muscle cells from the circular muscle layer of the dog colon showed a mechanical threshold... more Smooth muscle cells from the circular muscle layer of the dog colon showed a mechanical threshold of -44 mV. No gradient in mechanical threshold was measured between the cells from the submucosal and myenteric plexus surface. The threshold was passed during the upstroke and the plateau phase of the spontaneous slow-wave activity from cells at the submucosal surface and by spike potentials occurring mainly in cells at the myenteric plexus surface and sporadically in cells at the submucosal surface. Carbachol-induced specific changes in electrical and mechanical activities that were inhibited by calcium influx blockade are as follows: 1) increase in slow-wave duration; 2) decrease in plateau potential; 3) enhancement of spiking activity; and 4) increase in contractility. This indicates that calcium influx is significantly increased in the presence of carbachol in cells at both surfaces of the circular muscle layer. The increase in calcium influx could be the result of a direct action ...

Progress in clinical and biological research, 1990

Nature Nanotechnology, 2014

There is a need for safer and improved methods for non-invasive imaging of the gastrointestinal t... more There is a need for safer and improved methods for non-invasive imaging of the gastrointestinal tract. Modalities based on X-ray radiation, magnetic resonance and ultrasound suffer from limitations with respect to safety, accessibility or lack of adequate contrast. Functional intestinal imaging of dynamic gut processes has not been practical using existing approaches. Here, we report the development of a family of nanoparticles that can withstand the harsh conditions of the stomach and intestine, avoid systemic absorption, and provide good optical contrast for photoacoustic imaging. The hydrophobicity of naphthalocyanine dyes was exploited to generate purified ∼20 nm frozen micelles, which we call nanonaps, with tunable and large near-infrared absorption values (>1,000). Unlike conventional chromophores, nanonaps exhibit non-shifting spectra at ultrahigh optical densities and, following oral administration in mice, passed safely through the gastrointestinal tract. Non-invasive, non-ionizing photoacoustic techniques were used to visualize nanonap intestinal distribution with low background and remarkable resolution, and enabled real-time intestinal functional imaging with ultrasound co-registration. Positron emission tomography following seamless nanonap radiolabelling allowed complementary whole-body imaging.

Pancreas, 2011

Ramon y Cajal discovered interstitial cells in the pancreas associated with intrinsic nerves. It ... more Ramon y Cajal discovered interstitial cells in the pancreas associated with intrinsic nerves. It was our aim to provide evidence for or against the hypothesis that the pancreatic duct harbors interstitial cells of Cajal (ICCs) that may function as pacemakers for duct motility. We used immunohistochemistry using c-Kit as the ICC marker and protein gene product 9.5 for nerves. Electron microscopy further characterized the cells and their interrelationships. c-Kit-positive cells were associated with smooth muscle cells and nerve fibers of the duct wall and were rich in mitochondria, rough endoplasmic reticulum, and intermediate filaments; they possessed occasional caveolae and had a discontinuous basal lamina. They were connected by small gap junctions to each other and to smooth muscle cells. c-Kit-positive cells around large blood vessels were similar. c-Kit-positive cells within acini were similar in structure but were not associated with smooth muscle cells. The c-Kit-positive cells around the main duct were identified as ICCs and have the morphological criteria to likely function as pacemaker cells for the previously observed spontaneous rhythmic pancreatic duct contractions. Interstitial cells of Cajal around the large blood vessels likely affect vessel wall rhythmicity.

Journal of Neurochemistry, 1978

ABSTRACT

Gastroenterology, 1998

GASTROENTEROLOGY 1998;114:598-601

Frontiers in Neuroscience, 2013

Experientia, 1992

The functioning of a group of cells as a tissue depends on intercellular communication; an exampl... more The functioning of a group of cells as a tissue depends on intercellular communication; an example is the spread of action potentials through intestinal tissue resulting in synchronized contraction. Recent evidence for cell heterogeneity within smooth muscle tissues has renewed research into cell coupling. Electrical coupling is essential for propagation of action potentials in gastrointestinal smooth muscle. Metabolic coupling may be involved in generation of pacemaker activity. This review deals with the role of cell coupling in tissue function and some of the issues discussed are the relationship between electrical synchronization and gap junctions, metabolic coupling, and the role of interstitial cells of Cajal in coupling.

Canadian Journal of Physiology and Pharmacology, 2001

Muscarinic receptor mediated membrane currents and contractions were studied in isolated canine c... more Muscarinic receptor mediated membrane currents and contractions were studied in isolated canine colon circular smooth muscle cells. Carbachol (105 M) evoked a slow transient inward current that was superimposed by a transient outward current at holding potentials greater than 50 mV. Carbachol contracted the cells by 70 ± 2%. The effects of carbachol were blocked by atropine (106 M), tetraethyl ammonium (20 mM), and BAPTA-AM (25 mM applied for 20 min). The inward current and contraction were not sensitive to diltiazem (105 M), nitrendipine (3 × 107 M), niflumic acid (105 M), or N-phenylanthranilic acid (104 M), but were gradually inhibited after repetitive stimulations in Ca2+ free solution. Ni2+ (2 mM) inhibited the inward current by 67 ± 4%. The inward current reversed at +15 mV. The outward component could be selectively inhibited by iberiotoxin (20 nM) or by intracellular Cs+. Repeated stimulation in the presence of cyclopiazonic acid (CPA, 3 µM) inhibited the carbachol-in...

Canadian Journal of Physiology and Pharmacology, 1988

Electrophysiological effects of anaphylactic stimulation of rat basophilic leukemia cells (RBL-2H... more Electrophysiological effects of anaphylactic stimulation of rat basophilic leukemia cells (RBL-2H3) were studied using conventional microelectrodes. Stimulation of passively sensitized cells by anti-immunoglobulin E resulted in hyperpolarization followed by depolarization. These changes in membrane polarization were associated with a decrease in input membrane resistance. No effect of anaphylactic stimulation was seen in Ca2+-free solution or when Ca2+ influx was blocked by Co2+, but it was mimicked by the Ca2+ ionophore A-23187. This suggests that the changes in ionic conductances were associated with calcium influx. These results support the hypothesis that membrane conductance changes are involved in the stimulus-secretion process of the RBL-2H3 cells.

Canadian Journal of Physiology and Pharmacology, 1987

Spontaneous and current-induced electrical activity was recorded intracellularly to resolve the c... more Spontaneous and current-induced electrical activity was recorded intracellularly to resolve the controversy whether or not the circular muscle layer of the colon generates spiking activity. Particularly in the first hour after mounting the tissue in the organ bath, spikes were recorded at both the submucosal and the myenteric plexus side of the muscle layer. Spikes were seen as part of the slow wave upstroke in the submucosal surface cells, and spikes occurred both at the upstroke potential and superimposed on the plateau potential in myenteric plexus surface cells. Spikes increased the force of contraction. The study supports earlier claims using extracellular recording techniques that circular muscle cells generate spiking activity, particularly in the presence of depolarizing stimuli, and that spikes contribute to contractile activity.