Biomedical subjects

M Schmelz

Publications and source records attributed to M Schmelz.

At least 73 records · Page 4Linked to original sources

PubMed1999

Pain and inflammatory hyperalgesia induced by intradermal injections of human platelets and leukocytes.

Acute and prolonged inflammatory processes, induced by intradermal injections of autologous platelet preparations, leukocytes, platelet-leukocyte mixtures and vehicle solutions, were monitored in 20 human subjects for up to 48 h. Psychophysical methods were employed to assess the time course of pain response, and the development of hyperalgesia. Time course of the axon reflex erythema was analysed by computer based videography. Injections of functionally intact platelets [4.4 x 10(7)+/- 0.6 x 10(7)in 50 µl (mean +/- SEM)] caused distinct pain sensations [median pain rating 7.25 (25-75%: 6.5-7.5) on a scale form 0-10]. Both platelets injected through a microfilter (0.2 µm) and heat-inactivated platelets induced similar initial pain response; however, pain duration was significantly shorter than for intact platelets. Control injections of leukocytes (5.4 x 10(6)+/- 3.7 x 10(6)in 50 µl) and of vehicle solutions only caused minute pain sensations.Although platelet concentration in the mixture was only 50%, platelet/leukocyte mixtures produced axon reflex erythema that were significantly larger than those seen with naive platelets alone (11.1 +/- 2.3 vs 8.3 +/- 0.8 cm(2)). Intact platelets and heat-inactivated platelets both induced mechanical hyperalgesia and skin indurations at the injection site. Both reactions peaked between 6 and 24 h after the injection and disappeared within 48 h. Neither hyperalgesia, nor the development of indurations was noted at the injection sites of filtered platelets and vehicle solutions. Leukocyte injections induced hyperalgesia and indurations only in samples with a platelet contamination of more than 50 000 cells/µl. We conclude that platelets induce acute pain responses due to a soluble factor, whereas the development of hyperalgesia and the formation of indurations depends on a membrane-bound factor. Moreover, platelets and leukocytes act synergistically in nociceptor activation. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

PubMed1999

The effects of intradermal fentanyl and ketamine on capsaicin-induced secondary hyperalgesia and flare reaction.

UNLABELLED: In this study, we evaluated the effects of intradermal fentanyl and ketamine on capsaicin-induced hyperalgesia and axon-reflex flare. In addition, we obtained dose-response curves for possible local anesthetic effects. Saline (200 microL) and either fentanyl (1 microg or 10 microg in 200 microL) or ketamine (100 microg or 1000 microg in 200 microL) were injected simultaneously into the central volar forearm of 12 healthy volunteers. Nine minutes later, capsaicin (10 microg in 20 microL) was injected intracutaneously exactly between the two injection sites. Areas of touch-evoked allodynia and pinprick hyperalgesia, as well as intensity of pinprick hyperalgesia at the injection sites and axon-reflex flare, were evaluated. Fentanyl did not affect the area or intensity of secondary hyperalgesia. Only the larger concentration of fentanyl locally diminished axon-reflex flare without affecting mechanical detection thresholds. Inhibitory effects of ketamine on intensity of secondary hyperalgesia and axon reflex flare were observed only in the larger concentration. However, this concentration also clearly elevated mechanical detection thresholds. No inhibitory effects of ketamine in the smaller concentrations were observed. We conclude that fentanyl inhibits neuropeptide release on peripheral application without modulating secondary hyperalgesia. Ketamine failed to inhibit both secondary hyperalgesia and axon reflex flare as long as nonlocal anesthetic concentrations were applied. IMPLICATIONS: We investigated the peripheral effects of fentanyl and ketamine on capsaicin-induced hyperalgesia and axon-reflex flare. In large concentrations, the opioid diminished axon-reflex flare without effects on secondary hyperalgesia. We found no evidence for the involvement of endogenous glutamate in secondary hyperalgesia or axon reflex flare.

Adult↗

PubMed1999

Peripheral antihyperalgesic effect of morphine to heat, but not mechanical, stimulation in healthy volunteers after ultraviolet-B irradiation.

UNLABELLED: The objective of this study was to evaluate direct peripheral analgesic effects of morphine using a peripheral model of hyperalgesia and the technique of IV regional anesthesia (IVRA), thus allowing the differentiation between central and peripheral mechanisms of action. Two spots on the ventral sides of both forearms in 12 volunteers were irradiated with ultraviolet (UV)-B to induce thermal and mechanical hyperalgesia. One day after the induction of the inflammatory reaction, 40 mL of morphine hydrochloride 0.01% was administered via IVRA. Calibrated heat and phasic mechanical stimuli were applied to differentially determine impairments of tactile and nociceptive perception. Touch and phasic mechanical stimuli of noxious intensity to normal skin did not reveal altered responsiveness caused by morphine. In contrast, the administration of morphine significantly increased heat pain thresholds in the UV-B-pretreated skin areas. The peripheral antihyperalgesic effects of morphine were demonstrated only in inflamed skin areas. Direct central analgesic effects were ruled out by the lack of measurable plasma concentrations of morphine and its metabolites. Morphine 0.01% significantly diminished thermal, but not mechanical, hyperalgesia by a peripheral mode of action, which suggests inhibition of effector pathways leading to heat, but not mechanical, sensitization. IMPLICATIONS: The peripheral analgesic effects of morphine were studied using modified IV regional anesthesia. When administered 1 day after the induction of dermal inflammation, morphine 0.01% diminished heat, but not primary mechanical, hyperalgesia. Therefore, suppression of mechanical hyperalgesia seen in previous studies could be predominantly due to inhibition of secondary (central) mechanical hyperalgesia.

Adult↗

PubMed1999

Measurement of corneal sensitivity to mechanical and chemical stimulation with a CO2 esthesiometer.

PURPOSE: To develop an instrument to measure corneal sensitivity. Mechanical stimulation was performed with increasing air flow. Chemical stimulation consisted of local pH decreases induced by a mixture of air and CO2 at different concentrations. METHODS: Air and 98.5% CO2 were mixed with an electronic, proportional-direction control valve to obtain gas mixtures from 0% to 80% CO2. The regulated outflow of gas was carried to a probe mounted on a slit lamp holder, where it was warmed and its CO2 concentration monitored. An electronic valve directed gas pulses of controlled duration to the cornea. Corneal stimulation was performed in 17 young human subjects. The intensity of the experienced sensation was recorded in a continuous visual analog scale (VAS). To obtain threshold values and intensity-response curves, 3-second pulses were applied. For mechanical stimulation, air pulses of increasing flow were used. For chemical stimulation, gas mixtures of increasing CO2 concentration at subthreshold flow and CO2 in stepped increases of 5% was applied. RESULTS: Mechanical and chemical stimulation of the cornea evoked a brief sensation of irritation. Mechanical threshold (flow values) varied among subjects but were reproducible within each subject and were higher with warmed air. The magnitude of the sensation increased proportionally to the flow of air. The mean chemical stimulation threshold (CO2 concentration) was 25% +/- 3%. Increases in CO2 concentration from 10% to 80% augmented proportionally the intensity of the evoked sensation. CONCLUSIONS: The gas esthesiometer, which combines variable air flow and CO2 concentrations, permits application to the cornea of mechanical stimuli of controlled force and pH reductions of increasing magnitude. This instrument may be useful in a separate exploration of mechanical and chemical sensitivity of the cornea in human subjects.

Adult↗

PubMed1998

Characterization of the active site of a hydrogen sensor from Alcaligenes eutrophus.

A third hydrogenase was recently identified in the proteobacterium Alcaligenes eutrophus as a constituent of a novel H2-sensing multicomponent regulatory system. This regulatory hydrogenase (RH) has been overexpressed in cells deficient in both the NAD+-reducing [NiFe]-hydrogenase and the membrane-bound [NiFe]-hydrogenase. EPR, FTIR and activity studies of membrane-free extracts revealed that the RH has an active site much like that of standard [NiFe]-hydrogenases, i.e. a Ni-Fe site with two CN- groups and one CO molecule. Its catalytic power is low, but the RH is always active, insensitive to oxygen, and occurs in only two redox states.

Binding Sites↗

PubMed1998

A novel type of adhering junction in an epithelioid tumorigenic rat cell culture line.

Two major types of plaque-bearing adhering junctions are commonly distinguished: the actin microfilament-anchoring adhaerens junctions (AJs) and the desmosomes anchoring intermediate-sized filaments (IFs). Both types of junction usually possess the common plaque protein, plakoglobin, whereas the other plaque proteins and the transmembrane cadherins are mutually exclusive. For example, AJs contain E-, N-, or P-cadherin in combination with alpha- and beta-catenin, vinculin and alpha-actinin, whereas in desmosomes, desmogleins and desmocollins are associated with desmoplakin and one or several of the plakophilins (PP1-3). Here we describe a novel type of adhering junction comprising proteins of both AJs and desmosomes and the tight junction (TJ) plaque protein, ZO-1, in a newly established, liver-derived tumorigenic rat cell line (RMEC-1). By immunofluorescence microscopy, cell-cell contacts are characterized by mostly continuous-appearing lines which are usually resolved by electron microscopy as extended arrays of closely spaced small plaque subunits. These plaque-covered regions are positive for plakoglobin, alpha- and beta-catenin, the arm-repeat protein p120, vinculin, desmoplakin and protein ZO-1. They are positive for E-cadherin in cultures early on in passaging, but tend to turn negative for all known cadherins in densely grown cultures. On immunoblotting SDS-PAGE-separated proteins from dense-grown cell monolayers, "pan-cadherin" antibodies have reacted with a band at approximately 140 kDa, identified as N-cadherin by peptide fingerprinting of the immunoprecipitated protein, which for reasons not yet clear is modified or masked in immunolocalization experiments. The exact histological derivation of RMEC-1 cells is not known. However, the observations of several endothelial markers and the fact that all cells are rich in IFs containing vimentin and/or desmin, while only subpopulations also reveal IFs containing CKs 8 and 18, is suggestive of a mesenchymal, probably endothelial origin. We discuss the molecular relationship of this novel type of extended junction with other types of adhering junctions.

Animals↗

PubMed1998

Effects of antihyperalgesic drugs on experimentally induced hyperalgesia in man.

In a double-blind, cross-over study, ibuprofen (600 mg), a peripherally-acting selective kappa-opioid receptor agonist (7.5 mg), or placebo were given orally in experiments on healthy volunteers 1 h before assessment of pain thresholds to radiant heat and of pain ratings to controlled mechanical impact stimuli. Mechanical and thermal hyperalgesia had been induced 24 h before by irradiating skin patches on the ventral side of the upper leg. UVB irradiation induced mechanical and thermal hyperalgesia at radiation dosages of three times the minimal erythema dose. UVA irradiation resulted in an immediate erythema and a delayed tanning of the skin, however, no hyperalgesia was observed. For comparison another model of mechanical hyperalgesia was applied in the same experiments which has been previously proven sensitive to non-steroidal anti-inflammatory drugs (NSAIDs). In this model hyperalgesia was assessed, which develops during repetitive pinching of skin folds (pinch model). Ibuprofen significantly diminished heat and mechanical hyperalgesia induced by UVB, but had no effect on pain responses obtained from untreated skin. It also had an antihyperalgesic effect in the pinch stimulus paradigm. In contrast, the kappa-agonist showed no antihyperalgesic efficacy in the chosen models. It is concluded that the UVB model, as the pinch model, is suitable for establishing antihyperalgesic effects of NSAIDs, but probably not of kappa-receptor agonists, in healthy human volunteers. Compared to the pinch stimulus model, the UVB model offers additional advantages: (a) drugs may be tested after induction of the skin trauma by UV and this situation is more similar to the clinical use of antihyperalgesic drugs. (b) Since mechanical and thermal hyperalgesia is induced by UVB, drug effects can be tested upon both forms of hyperalgesia.

Adult↗

PubMed1998

Low-dose lidocaine suppresses experimentally induced hyperalgesia in humans.

BACKGROUND: The antinociceptive effects of systemically administered local anesthetics have been shown in various conditions, such as neuralgia, polyneuropathy, fibromyalgia, and postoperative pain. The objective of the study was to identify the peripheral mechanisms of action of low-dose local anesthetics in a model of experimental pain. METHODS: In a first experimental trial, participants (n=12) received lidocaine systemically (a bolus injection of 2 mg/kg in 10 min followed by an intravenous infusion of 2 mg x kg(-1) x h(-1) for another 50 min). In a second trial, modified intravenous regional anesthesia was administered to exclude possible central analgesic effects. In one arm, patients received an infusion of 40 ml lidocaine, 0.05%; in their other arm, 40 ml NaCl, 0.9%, served as a control. In both trials, calibrated tonic and phasic mechanical and chemical (histamine) stimuli were applied to determine differentially the impairment of tactile and nociceptive perception. RESULTS: Mechanical sensitivity to touch, phasic mechanical stimuli of noxious intensity, and heat pain thresholds remained unchanged after systemic and regional application of the anesthetic. In contrast, histamine-induced itch (intravenous regional anesthesia), axon reflex flare (systemic treatment), and development of acute mechanical hyperalgesia during tonic pressure (12 N; 2 min) of an interdigital web was significantly suppressed after both treatments. CONCLUSIONS: Increasing painfulness during sustained pinching has been attributed to excitation and simultaneous sensitization of particular Adelta- and C-nociceptors. This hyperalgesic mechanism seems to be particularly sensitive to low concentrations of lidocaine. These findings confirm clinical experience with lidocaine in pain states dominated by hyperalgesia.

Adult↗

PubMed1998

Innervation territories of single sympathetic C fibers in human skin.

Microneurography techniques were used to record action potentials from unmyelinated nerve fibers (C fibers) in the cutaneous fascicles of the peroneal nerve in healthy volunteers. C units were identified by their long latency responses to electrical stimulation of their terminals in the skin. Their responsiveness to mechanical or heat stimuli applied to the skin or to sympathetic reflex provocation tests was determined by transient slowing of conduction velocity following activation (marking technique). In a sample of 381 C units, 59 were unresponsive to mechanical and thermal stimulation of their endings, but responded to sympathetic reflex provocation tests, e.g., arousal or deep inspiration. They were classified as sympathetic efferent units. On average, conduction velocities of sympathetic units were lower (0.78 +/- 0.12 m/s, mean +/- SD) than those of mechano-heat (CMH) or mechanoresponsive (CM) afferent C units (0.91 +/- 0.14 m/s). Endings of most of the sympathetic units were located in the skin of toes or in the foot dorsum. Innervation territories of 16 sympathetic units were mapped by means of conditioning transcutaneous electrical stimuli. Twelve units had one continuous skin territory, whereas two units had two and two other units had three and five separate territories, respectively. The mean innervated area was 128 mm2 (range: 24-350 mm2). Innervation territories of sympathetic units were of approximately the same size in different skin regions on the lower leg, foot, or toes. Based on responses to whole body cooling and warming, two units were tentatively classified as vasoconstrictor and sudomotor units, respectively. Eleven units were tested for responsiveness to iontophoresis of acetylcholine in their innervation territories. In five of them, activity was induced that was not due to central reflex activity but instead due to antidromic activation from the peripheral terminals. Iontophoresis of saline or histamine was ineffective. These findings confirm the existence of excitatory cholinergic receptors in the terminal membrane of some sympathetic units, possibly sudomotors.

Acetylcholine↗

PubMed1997

Specific C-receptors for itch in human skin.

In microneurography experiments 56 unmyelinated nerve fibers were studied in the cutaneous branch of the peroneal nerve of healthy volunteers. Units were identified with the "marking" technique as mechanically and heat-responsive (CMH; n = 30), heat-responsive (CH; n = 13), or unresponsive to mechanical and heat stimulation (CMiHi; n = 13). None of the units showed spontaneous activity. These units were tested for responsiveness to iontophoresis of histamine (1 mA, 20 sec) from a small probe (diameter, 6 mm), which induced itch sensations lasting several minutes. Twenty-three units were unresponsive to histamine, and 25 units responded weakly with a few spike discharges after iontophoresis. Eight units, however, responded with sustained discharges to histamine, and their discharge patterns were matching the time course of the itch sensations. All C-units in this group were mechanically insensitive, and five of them were heat-responsive. They had very low conduction velocities of only 0.5 m/sec, on average, which is significantly lower than conduction velocities of the "polymodal" CMH units. This slow conduction velocities attributable to small axon diameters may be one reason why these units have not been encountered in previous studies. Histamine-sensitive C-units had very large innervation territories extending up to a diameter of 85 mm on the lower leg. We conclude that these C-fibers represent a new class of afferent nerve fibers with particularly thin axons but excessive terminal branching. This type of C-fiber probably represents the afferent units long searched for mediating itch sensations.

Adult↗

PubMed1997

Plasma extravasation and neuropeptide release in human skin as measured by intradermal microdialysis.

Time course of plasma extravasation in neurogenic inflammation elicited by histamine iontophoresis and topical capsaicin application was measured in vivo by a modified intradermal microdialysis technique in humans. Single linear plasmapheresis fibers were inserted intracutaneously at the volar forearm and perfused with Ringer's solution (4 microl/min) with one microdialysis fiber located at the planned stimulation site and a second inside the axon reflex area. Protein concentration in the dialysate increased by 300% in the histamine wheal but no increase was found in the surrounding flare area. There was no protein extravasation in the skin treated with capsaicin nor in the surrounding flare region. Inside the histamine-induced flare reaction a significant increase of calcitonin gene related peptide (CGRP) was found, whereas the increase of substance P (SP) was not significant.

Adult↗

PubMed1997

Intracutaneous injections of platelets cause acute pain and protracted hyperalgesia.

Suspensions of autologous, washed platelets were intracutaneously injected at the volar forearms of healthy volunteers. Injections of serum and vehicle served as control. Subjects and experimenter were blind with respect to the sequence of injections. In contrast to serum and solvent solution, platelets induced graded burning pain lasting several minutes. Platelet but not serum or vehicle injections dose-dependently caused large axon-reflex flares. At the site of platelet injections an induration developed and in parallel delayed mechanical and heat hyperalgesia was observed. Hyperalgesia to pressure and impact stimulation reached a maximum after 6 h and subsided during the following 48 h. Also, the threshold to heat stimuli decreased moderately by about 1 degree C, on average, after 24 h. Neither indurations nor hyperalgesia could be detected at the injection sites of serum or vehicle. The pathophysiological significance of this new inflammatory model for the research of posttraumatic hyperalgesia is discussed.

Acute Disease↗

PubMed1997

Innervation territories of mechanically activated C nociceptor units in human skin.

Innervation territories of mechanically activated C nociceptor units in human skin. J. Neurophysiol. 78: 2641-2648, 1997. Innervation territories of single mechanically activated C nociceptors in the skin of the leg and foot were explored in normal human subjects. Microneurographic recordings were obtained in the peroneal nerve from 70 mechano-heat responsive (CMH) and 7 mechano-(but not heat) responsive (CM) units. Units were identified by their constant long-latency response to intracutaneous electrical stimulation of their terminals. Responsiveness to mechanical, heat, or transcutaneous electrical stimuli was verified by transient slowing of conduction velocity after activation by such stimuli. We determined their thresholds to mechanical stimuli (mean 33.7 mN, median 30 mN, range 3-750 mN) and heat (mean 42.5 degrees C, median 42.5 degrees C, range 37-49 degrees C). Most mechano-receptive fields (mRFs) were found on the foot dorsum (60 units) and some on the lower leg (14 units) and toes (3 units). Most units had one continuous mRF, but 10 units had more complex fields. Areas of mRFs mapped with a von Frey filament (750 mN) ranged from 10 to 363 mm2 (mean, 106 mm2). The mRFs were oval or irregularly shaped with greatest diameters ranging from 3 to 45 mm. Mean areas of mRFs were largest on the lower leg (198 mm2), smaller on the foot dorsum (88 mm2), and smallest on the toes (35 mm2). Forty-nine of the 77 units had identical mRFs and electro-receptive fields (eRFs). Twenty-six units had larger eRFs than mRFs, whereas the opposite was found for two units only. Areas of eRFs ranged from 16 to 511 mm2 (mean 121 mm2). An estimate of the innervation density based on the present data and the presumed number of C fibers in cutaneous fascicles of the peroneal nerve suggests a considerable overlap of nociceptive endings in the skin. Such overlapping nociceptor innervation in the skin allows for substantial spatial summation in response to punctate noxious stimuli, which may be a prerequisite for high accuracy in localizing painful events from a C-fiber input. The reduction in size of innervation territories distally allows for finer discrimination of spatial dimensions of noxious stimuli distally as compared with proximal regions of the extremities. Mean maximal diameters of the mechano-receptive fields of CMH and CM units on the lower leg (22.3 mm) and foot (15.3 mm) are of similar size as the radius of axon reflex flares evoked by noxious mechanical stimuli in these regions.

Adult↗

PubMed1996

Topical acetylsalicylate attenuates capsaicin induced pain, flare and allodynia but not thermal hyperalgesia.

The effect of acetylsalicylic acid (ASA) on capsaicin-evoked activation of cutaneous nociceptors was tested in a double blind study in 10 volunteers. Capsaicin (2% in ethanol) was applied topically for 30 min. Topical ASA (0.25 g/ml) reduced pain intensity and axon reflex flare size. Also, areas of secondary hyperalgesia to light touch and pin-prick were diminished. In contrast, capsaicin-induced heat hyperalgesia was unaffected by ASA. It is concluded that ASA counteracts the excitatory effects of capsaicin on nociceptors and mechanical hyperalgesia but not its sensitizing action to heat.

Administration, Topical↗

PubMed1996

Limitation of sensitization to injured parts of receptive fields in human skin C-nociceptors.

Unmyelinated cutaneous mechano-heat fibers (CMH) in the peroneal nerve of healthy human volunteers were studied by means of a "marking" technique which allows stable recordings from identified single units over extended periods. Mechanoreceptive field sizes were 105 +/- 13 mm2 in 25 units. These large receptive fields indicate extensive terminal branching of C fibers in the skin of foot and lower leg. Sensitization of CMHs was tested by assessment of thresholds for mechanical (von Frey hair) and heat stimuli before and after topical application of mustard oil (allyl isothiocyanate) and capsaicin (8-methyl-N-vanillyl-6-noneamide). While in a group of 14 CMHs the entire receptive field was treated with these irritant substances, in another group of 11 CMH units only parts of the receptive field were treated to check for signs of spreading sensitization through axon collaterals. Mustard oil application did not change mechanical thresholds, regardless of whether parts of or complete receptive fields were treated. However, mean heat thresholds dropped by 5.6 degrees C to 36.5 +/- 1.5 degrees C in completely treated receptive fields and by 5.7 degrees C to 37.3 +/- 3.4 degrees C in treated parts of receptive fields ("primary sensitization"). In contrast, heat thresholds in the nontreated parts did not change significantly (42.1 +/- 3.4 degrees C vs 41.2 +/- 3.9 degrees C), i.e. "secondary sensitization" to heat was lacking. The absence of primary sensitization to probing with von Frey hairs indicates that sensitization of insensitive C fibers and recruitment of insensitive axon collaterals may be more important for mechanical hyperalgesia than sensitization of conventional CMH units-apart from the contribution of central mechanisms. The lack of spread of sensitization to untreated parts of the receptive fields o CMHs ("secondary sensitization") indicates that this fiber group is probably not involved in any form of secondary hyperalgesia to heating.

Adult↗

PubMed1996

Proliferative Merkel cells were not detected in human skin.

The fetal development of Merkel cells-neuroendocrine cells of the skin - has been a matter of debate for a long time. Recent results have helped to confirm their intraepidermal development in humans. Simple epithelial cytokeratins (CK) nos. 8, 18, 19 and 20 are well established markers at the light microscopic level. These cells could be detected from fetal week 8 within the epidermis with an enormous increase during the following weeks. This gives rise to the question as to whether Merkel cells are undergoing mitoses or whether they are derived from basal keratinocytes. We studied fetal and adult skin using antibodies to simple epithelial CK and to Ki67, a human nuclear cell proliferation-associated antigen in an attempt to answer these questions. In human adult and fetal skin of various stages we could not detect any Merkel cells undergoing cell division. These results suggest that Merkel cells are postmitotic cells to be renewed from undifferentiated keratinocytes with stem cell characteristics.

Adult↗

PubMed1996

Differences of bcl-2 protein expression between Merkel cells and Merkel cell carcinomas.

The bcl-2 gene, originally identified in B-cell lymphomas, encodes for proteins which may assume oncogenic functions by blocking apoptosis. Bcl-2 proteins are broadly distributed among various tissues, including epithelial ones. Within the skin, bcl-2 is strongly expressed in melanocytes, but its further distribution is yet unclear. The Merkel cells, neuroendocrine-epithelial cells of the skin, are present within the epidermis and hair follicles, mostly nerve-associated, and are believed to be postmitotic and long lived. Possibly they give rise to the malignant Merkel cell carcinomas. In the present study we investigated the bcl-2 expression on the protein level by means of immunohistochemical techniques including double confocal laser scanning microscopy, as well as on the RNA level by RT-PCR techniques, in Merkel cells, Merkel cell carcinomas, and cell lines. Merkel cells were identified by double staining for cytokeratins 20 or 8/18. We demonstrate that fetal epidermal and dermal Merkel cells are immunostained for bcl-2 protein, most of them clearly weaker than melanocytes. Adult Merkel cells also express bcl-2 protein very heterogeneously, mostly weak. In contrast, Merkel cell carcinomas are usually strongly positive for bcl-2 protein with some degree of heterogeneity. This is different from malignant melanomas in which bcl-2 expression is reduced as compared to normal melanocytes. Bcl-2 gene expression was also shown for Merkel cell carcinoma cell lines on both the mRNA and the protein level. Possibly bcl-2 protein expression is downregulated during the life span of Merkel cells, arguing that they may succumb to a certain cell turnover. The comparably high bcl-2 protein level in Merkel cell carcinomas may reflect peculiar biological and clinical characteristics.

Adult↗

PubMed1995

Neurogenic flare responses are heterogeneous in superficial and deep layers of human skin.

Infrared thermography and video image analysis were used to compare the development of the neurogenic flare response in deep and superficial skin layers. Neurogenic vasodilatation was induced by injection or iontophoretic application of histamine. Thermograms were recorded every 10 s to evaluate the local warming reaction. Color-video image analysis was used for computerized delineation of the visible flare. Images derived from video analysis were superimposed to the thermograms after linear transformation. The thermal reaction started within 10 s simultaneously at 2-5 distinct spots after histamine application at distances of 4-25 mm from the application site while the flare reaction seemed to spread from the application site when it became visible after a delay often exceeding 20 s. The visible flare but not the warming reaction was suppressed by topically applied local anesthetic (EMLA). Warming at focal spots was also observed during post-occlusive hyperemia. About 70% of these spots were identical to those activated by histamine. The results indicate that the vascular axon reflex is differently organized in different layers of the skin.

Adult↗