On the regulation of the expressed L-type calcium channel by cAMP-dependent phosphorylation

The Ca²⁺ channel subunits _1C-a and _1C-b were stably expressed in Chinese hamster ovary (CHO) and human embryonic kidney (HEK) 293 cells. The peak Ba²⁺ current (I _Ba) of these cells was not affected significantly by internal dialysis with 0.1 mM cAMP-dependent protein kinase inhibitor peptide (mPKI), 25 M cAMP-dependent protein kinase catalytic subunit (PKA), or a combination of 25 M PKA and 1 M okadaic acid. The activity of the _1C-b channel subunit expressed stably in HEK 293 cells was depressed by 1 M H 89 and was not increased by superfusion with 5 M forskolin plus 20 M isobutylmethylxanthine (IBMX). The _1C-a·₂·₂/ complex was transiently expressed in HEK 293 cells; it was inhibited by internal dialysis of the cells with 1 M H 89, but was not affected by internal dialysis with mPKI, PKA or microcystin. Internal dialysis of cells expressing the _1C-a·₂·₂/ channel with 10 M PKA did not induce facilitation after a 150-ms prepulse to +50 mV. The Ca²⁺ current (I _Ca) of cardiac myocytes increased threefold during internal dialysis with 5 M PKA or 25 M microcystin and during external superfusion with 0.1 M isoproterenol or 5 M forskolin plus 50 M IBMX. These results indicate that the L-type Ca²⁺ channel expressed is not modulated by cAMP-dependent phosphorylation to the same extent as in native cardiac myocytes.     

Influence of acute-phase proteins on the activity of natural killer cells

The effects of ₁-antitrypsin ( ₁,-AT), ₁,-acid glycoprotein ( ₁AGP), and haptoglobin (Hp), the main constituents of-globulin and which belong to acute phase proteins, on NK activity were examined using K562 cells as the NK target cells. Among the three proteins, ₁,-AT and ₁AGP had inhibitory effects on NK activity for fast target K562 cells. The,-AT preparations having the same protein concentration and a different trypsin inhibitory capacity (TIC) had an equal effect. Although ₁AT and ₁,-AGP equally reduced the NK activity, the mechanism involved in the reduction differed, in that the effect of ₁,-AT directed toward NK cells reduced their binding capacity with the target cells, ₁,-AGP probably interacts with a cytotoxic factor secreted from NK cells following effector-target interaction. These studies suggest that each of the acute-phase proteins, which increase following inflammation, inhibits NK cell function by two distinct mechanisms.     

Expression and ligand-binding function of the integrin α4β1 (VLA-4) on neural-crest-derived tumor cell lines

Human neural-crest-derived tumor cell lines, including three neuroblastomas, an astrocytoma, a glioblastoma, a rhabdomyosarcoma and a melanoma were screened for the expression of the integrin ₄₁ (VLA-4). The neuroblastomas IMR-32 and SK-N-SH, the astrocytoma 131-INI, the glioblastoma Fogerty and the rhabdomyosarcoma TE-671 expressed ₄₁ as determined by cytofluorometry and immunoprecipitation. Another neuroblastoma line, LA-N-1, did not express ₄₁. Analysis of immunoprecipitated ₄₁ showed that the ₄ subunit from the various cell types differed in relative molecular weight (M _r ). The variability in the observed M _r could be accounted for by differences in the levels of N-linked glycosylation. The observed variability in M _r did not appear to affect function since intact cells and solubilized ₄₁ bound to a synthetic peptide identical in sequence to the CS-1 region of the alternatively spliced IIICS domain of fibronectin, a known ₄₁, ligand.     

Calcium transients in skeletal muscle fibres under isometric conditions and during and after a quick stretch

Summary The transient change in the sarcoplasmic concentration of Ca²⁺ was measured in intact fibres isolated from the anterior tibial muscle of the frogLitoria moorei. The fibres had been injected with the calcium-sensitive dye arsenazo III and the change of the calcium concentration was calculated from the changes in light absorbance at 570,600 and 720 nm wavelengths. Absorbance and force were measured under three different conditions: (1) during a normal isometric twitch, (2) when a quick ramp-and-hold stretch had been applied to the fibre during onset of the contraction, and (3) when the fibre was allowed to contract isometrically at a length corresponding to the final length of the stretch. A method was devised to neutralize most of the movement artefacts encountered in such measurements. While the quick stretch caused substantial increase in the level and the duration of the contractile force such as originally described in whole muscle by A. V. Hill, the calcium transients appeared basically unaffected. It thus seems that the mechanism behind the phenomenon of the force enhancement lies at a step in the excitation-contraction coupling subsequent to the calcium release. From the present results, however, it is not clear whether the phenomenon is caused by an increase in the level of activation of the calcium-dependent regulatory system, or whether it is to be found in the acto-myosin interaction itself. The latter alternative would be consistent with the stiffness measurements published earlier.Abbreviations A absorbance at wavelength - A _,Ca calcium-dependent part of the absorbance - A _o calcium-independent part of the absorbance - A _,CaD ,A _,D absorbance at wavelength from the calcium-dye complex and the free dye, respectively - A _i intrinsic absorbance at wavelength - A change of absorbance - [Ca²⁺] _f change in intracellular concentration of free Ca²⁺ - D dye (i.e. arsenazo III) - _,CaD , _,D molar extinction coefficient for the calcium-dye complex and free dye at wavelength - EGTA ethyleneglycol-bis-(-aminoethyl ether) N,N¹-teteraacetic acid - I intensity of transmitted light - I _o, initial value ofI - I _,o intensity of the Ca-independent component of the transmitted light - I/I _o, change in intensity of transmitted light at wavelength normalized with respect to its initial value - K _D ^CaD apparent dissociation constant for calcium-dye complex - l optical path length - L change of fibre length - wavelength - MOPS morpholinopropanesulphonic acid - SL sarcomere length.     

Mechanical step variability during treadmill running

The present study was designed to study intra-individual step variability measured both on vertical displacement of the body (Z) and on step time (t) parameters by means of a kinematic arm and during treadmill running. A group of 17 subjects ran successively at 60%, 80%, 100% and 140% of their maximal aerobic velocity (v _amax). The total number of steps analysed was 6116. The absolute Z step variability (Z) ranged between 5 mm and 21 mm while the absolute t variability (t) ranged between 6 ms and 40 ms. Step variabilities were due to step asymmetry (from 38.5% to 48.5% of the step variability) and to stride variability. For submaximal velocities (60%, 80%, and 100%v _amax) both t and Z were independent of velocity or body dimensions whereas differences between subjects were significant (P < 0.01) for Z. On the other hand, variabilities were significantly increased when velocity was changed from submaximal to the 140%v _amax level. Furthermore, at submaximal levels Z was linked to the subject's energy cost of running (P < 0.05). Therefore, the intra-individual step variability should not be neglected in future studies on mechanical efficiency of running and it is suggested that, to obtain a good accuracy (better than 1%,P < 0.05) on mean value and variability of the mechanical parameters, measurements should be performed on at least 32–64 consecutive steps, which corresponds to about 15 to 20 s of running.     

Human chorionic gonadotropin in gastric carcinoma

Summary To investigate the production of human chorionic gonadotropin (hCG) in gastric carcinoma, 124 gastric carcinomas and a choriocarcinoma with adenocarcinoma were examined immunohistochemically, using anti-hCG and antibodies. In choriocarcinoma, many trophoblastic cells were synchronously positive for both subunits. In contrast, the distribution of hCG-subunits in gastric carcinoma was unbalanced with hCG in 39 and hCG in 63 cases. 26 cases contained and positive cells, whereas synchronous cells were extremely rare in four cases. Incidences of hCG-subunit-positivities were not different between early and advanced carcinomas. HCG-positive cells appeared endocrine-like in papillotubular carcinomas and some positive cells were argyrophilic in serial sections in 23 of 39 cases. HCG-positive cells were much more frequent in deranged glands, especially of microtubular-mucocellular carcinomas and most were not argyrophilic. In surrounding non-neoplastic mucosa, hCG-positive cells were more numerous with endocrine-like configurations, but hCG-positive cells were rarely present in deranged glands. Although subunit-profile of hCG in gastric carcinomas was different from that of normal, the difference may be quantitative: hCG-subunits may be expressed through an independent mechanism but commonly in gastric mucosa and carcinoma. These results are also discussed in relation to trophoblastic tumours arising in non-trophoblastic tissues.     

End-plate currents evoked by paired stimuli in frog muscle fibres

Using voltage-clamp techniques spontaneously occuring miniature end-plate currents (mepc) and nerve-evoked end-plate currents (epc) were recorded in frog glycerol-treated or cut muscle preparations. Epcs were induced by pairs of stimuli (the delay of the 2nd stimulus, t being 6 ms–30 s; one pair was delivered every 60–90 s). The decay time constant of the epc (_epc) was longer, the larger its quantal content despite the presence of active acetylcholinesterase (AChE). After treatment with anticholinesterases (prostigmine or armin, an irreversible inhibitor) this increase in _epc became more pronounced. When AChE was fully active the decay of the 1st epc ₁ was slightly faster than the decay of the 2nd epc ₂ only when the interstimulus interval was rather short (t<20 ms). Following treatment with anticholinesterases this difference between ₂ and ₁ could be determined even when t was as long as 30 s. In anticholinesterase-treated preparations was found to be inversely proportional to log t: a 50% increase in the decay time-constant of the 2nd epc occurred with t=120 ms. During continuous stimulation (10 impulses/s) _epc increased from the 1st to the 5–6th responses, but then decreased in parallel with the fall in the epc amplidude. The phenomenon of postsynaptic potentiation we observed could be readily abolished when quantal content was decreased by the presence of magnesium ions, but it was relatively unaffected when the receptor density was decreased by -bungarotoxin (-BuTX).The possible existence is discussed of two kinds of repetitive binding of ACh molecules, first, to free cholinoreceptors (a process which could be inhibited by -BuTX) and, second, to a complex of the cholinoreceptor plus one molecule of ACh (a process which is less sensitive to -BuTX blocking action).     

Studien über den Mechanismus der Immunhämolyse: Die Bindung der zweiten Komplementkomponente

Zusammenfassung Es wird die Reaktion EAC_1,4 + C₂ isoliert untersucht. Hierzu bietet man einer Charge von stufenweise aufgebautem EAC_1,4 ein von allen übrigen Komplementkomponenten befreites C₂-Präparat an. Bei der Reaktion kommt es zu einem meßbaren Schwund von C₂ im Überstand; gleichzeitig erwerben die Zellen die Fähigkeit, mit cheliertem Komplement zu lysieren. Die Reaktionsgeschwindigkeit ist bei 37° C hoch und bei 0° C gering. Für die Fähigkeit der Zellen, C₂ zu binden, ist nicht allein das gebundene C₄ maßgebend, sondern ein von C₁ nicht abgrenzbarer Zusatzfaktor. Demnach kommen dem C₁ nach seiner Bindung zwei Funktionen zu: Einmal vermittelt es die Bindung von C₄, zum anderen vermittelt es zusammen mit dem gebundenen C₄ die Bindung von C₂.Mit Unterstützung der Deutschen Forschungsgemeinschaft sowie der Gesellschaft der Freunde und Förderer der Medizinischen Akademie Düsseldorf.     

The VO2 response to exhaustive square wave exercise: influence of exercise intensity and mode

We investigated the oxygen uptake (O₂) response to exhaustive square wave exercise of approximately 2, 5 and 8 min duration in cycling and running. Nine males completed a ramp test and three square wave tests on a motorised treadmill and the same four tests on a cycle ergometer, throughout which gas exchange was assessed (Douglas bag method). The peak O₂ from the ramp test was higher for running than for cycling [mean (SD): 58.4 (2.8) vs. 55.9 (3.7) ml.kg^–1.min^–1; P=0.04]. However O_2max (defined as the highest O₂ achieved in any of the four tests) did not differ between running and cycling [60.0 (2.9) vs. 58.5 (3.3) ml.kg^–1.min^–1; P=0.15]. The peak O₂ was similar (P>0.1) for the 5 and 8 min square wave tests [98.5 (1.8) and 99.2 (2.3) %O_2max for running; 97.0 (4.2) and 97.5 (2.0) %O_2max for cycling] but lower (P<0.001) for the 2-min test [91.8 (2.5) and 89.9 (5.5) %O_2max for running and cycling respectively]. O₂ increased over the final two 30-s collection periods of the 2-min test for cycling [O₂=0.18 (0.15) l.min^–1; P<0.01] but not running [O₂=0.00 (0.09) l.min^–1; P=0.98]. We conclude that in the aerobically fit the peak O₂ for square wave running or cycling at an intensity severe enough to result in exhaustion in approximately 2 min is below O_2max. In running, O₂ plateaus at this sub-maximal rate.     

α 2Macroglobulin-proteinase complexes stimulate prostaglandin E2 synthesis by peritoneal macrophages

₂Macroglobulin is a proteinase inhibitor which is converted from its native form into an electrophoretically fast form by reaction with a proteinase or methylamine. All ₂M fast forms bind to a specific high-affinity receptor on macrophages. ₂M fast forms inhibit the interferon- (IFN)-induced increase in macrophage Ia expression. This study examined whether ₂M-proteinase complexes alter prostaglandin (PG) E₂ synthesis, and whether PGE₂ mediates ₂M fast forms effects on macrophage Ia expression. Culture with ₂M fast forms increased PGE₂ accumulation in the medium over control values in a dose-dependent manner. Culture with IFN alone did not increase PGE₂ levels, but potentiated the effect of ₂M-proteinase complexes on PGE₂ levels. Inhibition of PGE₂ synthesis did not alter the PGE₂ did suppress IFN-induced Ia expression. Thus, ₂M-proteinase complexes increase macrophage PGE₂ synthesis, but increased synthesis of PGE₂ or other cyclooxygenase products is not the mediator of antagonism of IFN-induced Ia expression by ₂M-proteinase complexes.     

Effects of interleukin-1β and tumor necrosis factor-α on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro

Osteoblasts play a pivotal role during the bioresponse of bone to agents that stimulate bone resorption and/or inhibit bone formation including hormones, polypeptide growth factors, and cytokines. We examined the cytokines interleukin-1-beta (IL-1) and tumor necrosis factor-alpha (TNF-) for their effects on osteoblastic proliferation and development and expression of alkaline phosphatase and the osteoblast-specific protein osteocalcin in a mineralizing environment. Primary rat osteoblast-like cells (ROB) and osteoblastic cell lines derived from rat (ROS 17/2.8) and human (MG-63) osteosarcomas were studied. IL-1 and TNF- were chosen because of their critical importance during the host response to local inflammatory stimuli. Qualitatively similar two- to threefold inhibition of osteocalcin synthesis by IL-1 and TNF- were observed in all three postconfluent bone-forming model systems. Because of the readily measurable concentrations of osteocalcin produced in our culture protocol, it was not necessary to enhance osteoblastic synthesis of osteocalcin by supplementation with 1,25(OH)₂-vitamin D₃, a treatment which exerts pleiotropic effects on osteoblasts. Under the constraints of our protocol, where alkaline phosphatase and mineralization were already elevated at the 14-day onset of treatment, neither of these phenotypic properties was sensitive to a three-day cytokine exposure. Differences were noted in proliferation, where only TNF- stimulated DNA synthesis in ROB cells, while both cytokines stimulated MG-63 cells. IL-1 and TNF- failed to alter ROS 17/2.8 DNA synthesis except at the highest doses (25 pM IL-1 and l nM TNF-) where inhibition was observed. These results further support the view that cytokine-mediated osteoblastic regulation can be relatively selective.     

Prostacyclin acts in rat gastric (fundic) mucosa via the intracellular ‘second messenger system’

Using a specific radioimmunoassay technique it seems that Prostacyclin (PG-I₂) has a strong effect on the cyclic nucleotide content of the rat gastric (fundic) mucosa. 1 min after an intragastric application of 100 g/kg PG-I₂ the cAMP-content and in the 5th min the cGMP-content showed a highly significant decrease. It seems that the basic mechanism of action of PG-I₂ is a typical hit and run effect, acting on the intracellular second messenger system.     

Distinct mechanism of human neuroblastoma cell adhesion to fibronectin

We investigated the adhesion of three morphologically distinct human neuroblastoma cell lines (NCG, GOTO and SK-N-DZ) to intact fibronectin, central cell binding domain fragment (CBF) and CS peptide-IgG conjugates in the fibronectin molecule. Each cell line was found to express different integrin fibronectin receptors ( _{3 1}, _{4 1} and ₅₁), although similarly attached on intact fibronectin. To CBF, NCG attached well, while GOTO moderately and SK-N-DZ poorly attached. Only GOTO adhered to CS1-IgG. RGDS inhibited the spreading of NCG and SK-N-DZ on intact fibronectin, but it barely inhibited that of GOTO. The analysis by fluorescence-activated cell sorting (FACS) revealed that NCG expressed abundant ₃₁ and ₅₁, but little ₄₁, while GOTO expressed a large amount of ₄₁ as well as ₅₁. SK-N-DZ was undetectable in any of these molecules, but expressed _v1, which was identified by immunoprecipitation and immunoblotting. Polyclonal antibody to _v3 inhibited the adhesion of SK-N-DZ but not that of NCG or GOTO on intact fibronectin. These results suggest the existence of a distinct mechanism of cell adhesion to fibronectin among human neuroblastoma cell lines. It remains to be determined if such heterogeneous adhesion properties are related to the unique metastatic character of human neuroblastoma.     

Peripheral nerve stimulation increases fos immunoreactivity without affecting type II Ca2+/calmodulin-dependent protein kinase, glutamic acid decarboxylase, or GABAA receptor gene expression in cat spinal cord

Expression patterns of the immediate early gene c-fos and of other genes including those for the -subunit of type II Ca²⁺/calmodulin-dependent protein kinase (CaMKII), 67-kDa glutamic acid decarboxylase (GAD), and the 1-, 2-, and 2-subunits of the GABA_A receptor were described in the spinal cord of normal cats and following peripheral nerve stimulation. As revealed by in situ hybridization histochemistry, CaMKII messenger RNA (mRNA) is normally distributed only in cells of Rexed's laminae I–IV, whereas GAD mRNA is expressed by subpopulations of cells in all laminae, with the heaviest hybridization signal found in laminae I–III and medial parts of laminae V and VI. The three GABA_A receptor subunits have varying expression patterns in the laminae. All of them are expressed by many cells located in the base of the dorsal horn and the intermediate zone, but only the 2-subunit is intensely expressed by motoneurons. Single-pulse, electrical stimulation of the sciatic or median and ulnar nerves of anesthetized cats at a pulse rate of 1/s for 6–8 h failed to induce observable changes in gene expression for CaMKII, GAD, or for the three subunits of the GABA_A receptor; although immunoreactivity for the protein products of c-fos (or c-fos-related genes) was markedly upregulated in some neurons of the dorsal horn and the intermediate zone. Therefore, under the present experimental conditions, upregulation of the immediate early gene c-fos (or c-fos-related genes) is not associated with changes in expression of late-effector genes potentially involved in central nervous system plasticity.     

β subunits determine the time course of desensitization in rat α3 neuronal nicotinic acetylcholine receptors

Standard two-electrode voltage-clamp techniques were used to investigate some of the pharmacological and functional properties of two types of rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes after pairwise injection of 34 or 32 mRNAs. Currents of several A amplitude were elicited by fast application of micromolar concentrations of either acetylcholine (ACh) or 1,1-dimethyl-4-piperazine (DMPP). The activation of either receptor type by DMPP showed cooperativity (Hill coefficient, n1.7) with a half-maximal activation concentration (EC₅₀) of 15–30 M. In 34 receptors, ACh displayed cooperativity (n=1.8) but was less efficacious than DMPP, yet its EC₅₀ was about equal to that of DMPP. Finally, in 32 receptors, ACh was much less efficacious and had a much lower EC₅₀. Desensitization induced by either DMPP or ACh was slow in 34 nicotinic ACh receptors but was rapid and extensive in 32 receptors, causing a significant proportion of the response to wane within the first few seconds of agonist application.     

Regulation of ICAM-1 Expression in Mouse Macrophages

In a mouse model of silica (SI) induced lung injury, SI exposure increases expression of intercellular adhesion molecule-1 (ICAM-1) on lung (alveolar/interstitial) macrophages and alveolar type II epithelial cells. To investigate the regulation of SI induced ICAM-1 expression on mouse macrophages, freshly isolated macrophages (alveolar, peritoneal) and macrophage cell lines (MH-S, RAW 264.7) were evaluated for ICAM-1 expression elicited by the particle silica ( quartz; 20 g/ml; 6 g/cm²) or the inflammatory cytokine, TNF (20 ng/ml). TNF significantly increased ICAM-1 expression in all cell types whereas SI elicited an increase in peritoneal macrophages (PM) and the cell line, MH-S. This pattern of increased expression was confirmed by immunocytochemistry. To investigate the regulation of ICAM-1 expression, PM were incubated with SI, TNF or media concomitantly with anti-TNF antibody, the antioxidant, NAC, or the iNOS synthase inhibitor, L-NAME. Both anti-TNF and NAC, but not L-NAME, inhibited elicited (TNF, SI) as well as constitutive (media) ICAM-1 expression. These data demonstrate that both inflammatory cytokines and inorganic particles can increase ICAM-1 expression on mouse macrophages and that this expression is mediated, in part, by TNF and reactive oxygen species.     

Effects of priming exercise intensity on the dynamic linearity of the pulmonary V̇O2 response during heavy exercise

Prior heavy-intensity exercise facilitates the pulmonary oxygen uptake (O₂) response during subsequent exercise, such that its kinetics returns towards first-order. To better understand this priming phenomenon, we investigated the effect of priming exercise, over a range of intensities, on the O₂ response to heavy-intensity cycle ergometry at a work rate of 50% [halfway between lactate threshold (LT) and O_2max]. Eight subjects performed two consecutive 6-min bouts separated by 6 min at 20 W. The first bout was each of: no warm-up control (CON), sub-lactate threshold (LT) at 80% of LT, and three supra-LT conditions (20%, 40%, and 60%). The O₂ response during the subsequent bout was evaluated using the effective time constant (), and the O₂ difference between minutes 3 and 6 (O_2(6–3)). The goodness-of-fit, indicative of first-order kinetics, was determined by the residual profile, and the mean square of errors (MSEr). The heart rate and blood lactate concentration ([La]r) just prior to the second bout were also measured. Compared with CON, and O_2(6–3) were significantly reduced following all supra-LT priming bouts, while the goodness-of-fit was significantly improved following 40% exercise. O_2(6–3) and [La]r were negatively correlated (P<0.05), unlike HR. In conclusion, prior exercise just above, but not below, LT facilitated the O₂ response in a threshold-like manner. Supra-LT priming exercise influenced the O₂ response allowing it to return to within as little as 12% from first-order (compared to ~50% in CON). The associated increases in circulating lactate and/or related factors seem to be centrally involved in this phenomenon.     

Examination of a purified A′ influenza virus preparation by potentiometry

Summary The potentiometric titration of a purified influenza A virus preparation revealed 100.7×10^–4 M base and 68.8 × 10^–4 M acid-binding capacity per g. of virus protein N. The titration curve was characterized by the following fourpK values:pK ₁ = 3.37;pK ₂ = 4.50;pK ₃ = 6.37, andpK ₄ = 9.75. The isoionic point was at pH 5.43.Attempt was made to identify the dissociating groups and it was found that the carboxylic groups (pK ₁ andpK ₂) may either be glutamyl or aspartyl groups, while the cationic groups are probably the imidazolium of histidine (pK ₃) and the -amino residues of lysine (pK ₄).Inaotivation of the hemagglutinating activity of the virus preparation by mild treatment with formaldehyde at pH 8.0 resulted in a simultaneous disappearence of the -amino groups of lysine (pK ₄). The same treatment at pH 9.0 resulted in the loss of all the cationic groups previously demonstrable.The possible role of the stable positive charges on the surface of the virus at physiological pH is discussed from the point of view of the physico-chemistry of the hemagglutination.     

Separate determination of the pulsatile elastic and viscous forces developed in the arterial wall in vivo

The viscoelastic behaviour of arteries in vivo is analyzed by separate representation of the purely elastic and the purely viscous properties, using natural pressure and diameter pulses of various dog arteries recorded under steady-state conditions. The circumferential wall stress () and the radius (r) of the mean wall layer are calculated as functions of time and the hysteresis of the -r diagram is represented. The stress is regarded as the sum of an elastic stress (_el) which is a function ofr, and a viscous stress (_vis) which is a function ofdr/dt. Thus _el=–_vis. Since the _el-r diagram must be free from hysteresis, the disappearance of the loop is the criterion that indicates that _el has been found._vis is formulated as a second degree polynomial ofdr/dt whose coefficients are determined using that criterion.The _el-r curve is always nonlinear and the elastic modulus increases with increasing radius. The _vis-dr/dt curve, too, is nonlinear. Its slope decreases with increasingdr/dt. The same applies to the wall viscosity (pseudoplastic behaviour). The nonlinear properties can be represented adequately by processing the experimental data in the time domain. Problems inherent in investigations based on the frequency domain, as reported in the literature, are pointed out.     

Zur Permeation der Serumeiweiße in die Haut und ihrer quantitativen Bestimmung am Modell der Cantharidenblase

Zusammenfassung Mittels chemischer und immunochemischer Methoden wurde vergleichend der Gehalt an Proteinen in Cantharidenblasen und Blutserum bestimmt. Erstmals werden auch quantitative Untersuchungen von Präalbumin, ₂-M-Globulin, Coeruloplasmin, Haptoglobin und Transferrin im Cantharidenblaseninhalt vorgenommen. Dabei fanden sich statistisch gesicherte Unterschiede zwischen Cantharidenblasen- und Seruminhalt im Sinne tieferer Werte in den Blasen bei Gesamteiweiß, Präalbumin abs., ₂-M-Globulin abs., ₂-Globulin abs. und rel.-%, Coeruloplasmin abs., -Globulin abs., Transferrin abs. und -Globulin abs. Albumin abs. und rel.-% wiesen signifikante Unterschiede in Richtung höherer Werte in den Cantharidenblasen auf. Das Makroglobulin ₂-M-Globulin passierte vergleichsweise schwerer die Capillarschranke zwischen Blut und Blaseninhalt als die niedermolekularen Proteine Coeruloplasmin, Haptoglobin und Präalbumin.

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Summary Comparative studies on Protein contents of blood and Cantharidin blisters were performed by means of chemical and immunochemical methods. For the first time quantitative measurements of Praealbumin, ₂-M-Globulin, Coeruloplasmin and Transferrin were done. Statistically significant differences between blister content and serum levels of proteins with higher values in the blisters were found in Total Protein, Praealbumin abs., ₂-M-Globulin abs., ₂-Globulin abs and rel.-%, Coeruloplasmin abs., -Globulin abs., Transferrin abs and -Globulin abs. Only Albumin abs. and rel.-% showed higher values in blisters as compared with the serum levels. Praealbumin, Haptoglobin and Coeruloplasmin were found to pass the capillary membrane, as measured by the difference between serum and blisters fluid content, more easily than the macromolecular protein ₂-M-Globulin.

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Herrn Prof. Dr.H. G. Bode, Direktor der Univ.-Hautklinik Göttingen, zum 60. Geburtstag am 31.8.64 verehrungsvoll gewidmet.