Medizin - Open Access LMU - Teil 05/22

1. The nature, distribution and function of rectifying channels in rat spinal root myelinated axons has been assessed with selective blocking agents and a variety of intracellular and extracellular recording techniques. 2. The electrotonic responses of roots poisoned with tetrodotoxin (TTX) to constant current pulses had fast (rise time much less than 1 ms) and slow components, which were interpreted in terms of Barrett & Barrett's (1982) revised cable model for myelinated nerve. Depolarization evoked a rapid outward rectification (time constant, tau approximately 0.5 ms), selectively blocked by 4-aminopyridine (4AP, 1 mM), and a slow outward rectification (tau approximately 15 ms), selectively blocked by tetraethylammonium (TEA, 1 mM) or Ba2+ (0.5 mM). Hyperpolarization evoked an even slower inward rectification, selectively blocked by Cs+ (3 mM) but not by Ba2+. 3. From the different effects of the blocking agents on the fast and slow components of electrotonus, it was deduced (a) that the inward rectification is a property of the internodal axon, (b) that the slow outward rectifier is present at the nodes, and probably the internodes as well, and (c) that the 4AP-sensitive channels have a minor nodal and a major internodal representation. 4. TEA and Ba2+ reduced the accommodation of roots and fibres not poisoned with TTX to long current pulses, whereas 4AP facilitated short bursts of impulses in response to a single brief stimulus. 5. TEA and Ba2+ also abolished a late hyperpolarizing after-potential (peaking at 20-80 ms), while 4AP enhanced the depolarizing after-potential in normal fibres, and abolished an early hyperpolarizing after-potential (peaking at 1-3 ms) in depolarized fibres. Corresponding to the later after-potentials were post-spike changes in excitability and conduction velocity, which were affected similarly by the blocking agents. Cs+ increased the post-tetanic depression attributable to electrogenic hyperpolarization. 6. The physiological roles of the three different rectifying conductances are discussed. It is also argued that the prominent ohmic 'leak conductance', usually ascribed to the nodal axon, must arise in an extracellular pathway in series with the rectifying internodal axon.

1. Double-barrelled ion-sensitive micro-electrodes were used to measure changes in the intracellular activities of K+, Na+ and Cl- (aiK, aiNa, aiCl) in glial cells of slices from guinea-pig olfactory cortex during repetitive stimulation of the lateral olfactory tract. 2. Base-line levels of aiK, aiNa and aiCl were about 66, 25 and 6 mM, respectively, for cells with resting potentials higher than -80 mV. During stimulation, intraglial aiK and aiCl increased, whereas aiNa decreased. Within about 2 min after stimulation the ion activities returned to their base-line levels. 3. The Cl- equilibrium potential was found to be close to the membrane potential (Em). There was also a strong correlation between changes of Em and aiCl. These observations indicate a high Cl- conductance of the glial cell membrane. 4. In the presence of Ba2+, the usual depolarizing response of the glial cells to a rise of the extracellular K+ activity (aeK) reversed into a membrane hyperpolarization. Furthermore, Ba2+ strongly reduced the stimulus-related rise of intraglial aiK. An additional application of ouabain blocked both the membrane hyperpolarization as well as the remaining rise of aiK. 5. In conclusion, our data show that glial cells in guinea-pig olfactory cortex slices possess at least two mechanisms of K+ accumulation. One mechanism is sensitive to the K+ channel blocker Ba2+ and might be a passive KCl influx. The other appears to be the electrogenic Na+/K+ pump, which can be activated by excess extracellular K+.

Double-barrelled ion-sensitive microelectrodes were used to measure changes in the intracellular activities of K+, Na+, and Cl- (aKi, aNai, aCli) in neurones of rat sympathetic ganglia and in glial cells of slices from guinea-pig olfactory cortex. In sympathetic neurones, carbachol and gamma-aminobutyric acid (GABA) produced a reversible decrease of aKi. The decrease of aKi during carbachol was accompanied by a rise of aNai, whereas in the presence of GABA decreases of aKi and aCli were seen. The reuptake of K+ released during the action of carbachol was completely blocked by ouabain, whereas furosemide inhibited the aKi recovery after the action of GABA. In glial cells, in contrast to the observations in the sympathetic neurones, aKi and aCli increased, whereas aNai decreased when neuronal activity was enhanced by repetitive stimulation of the lateral olfactory tract. It was found that barium ions and ouabain strongly reduced the activity-related rise of intraglial aKi in slices of guinea-pig olfactory cortex. These data show that mammalian neurones as well as glial cells possess several K+ uptake mechanisms that contribute to potassium homeostasis. Ouabain, furosemide, and Ba2+ are useful pharmacological tools to separate these mechanisms.

To study the mechanism of periodic paralysis, we investigated the properties of intact muscle fibers biopsied from a patient who had adynamia episodica hereditaria with electromyographic signs of myotonia. When the potassium concentration in the extracellular medium, [K]e, was 3.5 mmol/l, force of contraction, membrane resting potential, and intracellular sodium activity were normal, but depolarizing voltage clamp steps revealed the existence of an abnormal inward current. This current was activated at membrane potentials less negative than -80 mV, reached a maximum within 50 msec, and was not inactivated with time. The inward current was completely and reversibly blocked by tetrodotoxin, which indicates that it was carried by sodium ions. In a solution containing 9 mmol/l potassium, normal muscle would depolarize to -63 mV and yet be capable of developing full tetanic force upon stimulation. The muscle from the patient depolarized to -57 mV and became inexcitable, i.e., it was paralyzed. A contracture did not develop. Lowering of the extracellular pH did not influence the resting potential, but it effectively antagonized or prevented the paralytic effect of high [K]e by changing the inactivation characteristics of the sodium channels. Hydrochlorothiazide, which had a therapeutic effect on the patient, did not prevent paralysis in vitro. An abnormal rise of the intracellular sodium activity was recorded when the extracellular potassium concentration was raised to 10 mmol/l.

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/5767/1/5767.pdf Erdmann, E.; Kemkes, B.; Zähringer, J.; Riedel, Angelika; Ritter, D.; Schimak, M.; Glatthor, C.; Stangl, E.; Gerbes, Alexander L.; Arendt, Rainer M. ddc:610, Medizin

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6057/1/6057.pdf Gerbes, Alexander L. ddc:610, Medizin

The discovery of the first well-defined natriuretic hormone, the Atrial Natriuretic Factor (ANF), has prompted research on its impact on volume regulation in health and disease. The natriuretic, diuretic, and smooth muscle-relaxing properties suggest an important role of this novel hormone in pathophysiological states with sodium or volume retention, such as congestive heart failure or cirrhosis of the liver. Investigations on the implications of ANF in liver disease have been performed for little more than 1 year, and results are still controversial in many respects. At present, it seems very likely that there is no absolute deficiency of plasma ANF in patients with cirrhosis. Moreover, elevated plasma levels in cirrhotics with ascites have been reported by several groups. However, as yet, a molecular characterization of this increased immunoreactivity is still lacking. There is disagreement on the reduced release of and renal response to ANF in subgroups of cirrhotics; however, stimulus-response-coupling might be impaired. Further studies are needed to elucidate the pathophysiological implications and therapeutical potential of ANF in patients with chronic liver disease.

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6059/1/6059.pdf Gerbes, Alexander L. ddc:610, Medizin

The responses of rat neocortical neurons in vitro to iontophoretically applied N-methyl-d-aspartate (NMDA) were investigated by means of intracellular recording in the presence and absence of extracellular magnesium ions (Mg2+). At Mg2+-concentrations of 1.3 mM the neurons responded with a depolarization accompanied by an increase in membrane resistance. Upon removal of Mg2+ the NMDA-induced depolarization was markedly potentiated. However, even in neurons recorded from slices which were incubated in a Mg2+-free solution for 3–7 h, the NMDA response was still associated with a resistance increase, suggesting that the voltage-dependence of the NMDA-activated conductance is not exclusively determined by Mg2+.

1. The characteristics of long-duration inhibitory postsynaptic potentials (l-IPSPs) which are evoked in rat frontal neocortical neurons by local electrical stimulation were investigated with intracellular recordings from anin vitro slice preparation. 2. Stimulation with suprathreshold intensities evoked l-IPSPs with typical durations of 600–900 msec at resting membrane potential. Conductance increases of 15–60% were measured at the peak amplitude of l-IPSPs (150–250 msec poststimulus). 3. The duration of the conductance increases during l-IPSPs displayed a significant voltage dependence, decreasing as the membrance potential was depolarized and increasing with hyperpolarization. 4. The reversal potential of l-IPSPs is significantly altered by reductions in the extracellular potassium concentration. Therefore it is concluded that l-IPSPs in rat neocortical neurons are generated by the activation of a potassium conductance. 5. l-IPSPs exhibit stimulation fatigue. Stimulation with a frequency of 1 Hz produces a complete fatigue of the conductance increases during l-IPSPs after approximately 20 consecutive stimuli. Recovery from this fatigue requires minutes. 6. l-IPSPs are not blocked by bicuculline but are blocked by baclofen.

1. Intracellular recordings were obtained from neurones in layers 2 and 3 of the rat frontal neocortex in an in vitro slice preparation. Three distinct types of stimulation-evoked post-synaptic potentials were recorded in these neurones: excitatory post-synaptic potentials (e.p.s.p.s); bicuculline-sensitive, chloride-dependent inhibitory post-synaptic potentials (i.p.s.p.s) with times to peak of 20-25 ms (fast(f)-i.p.s.p.s); bicuculline-insensitive, potassium-dependent i.p.s.p.s with bicuculline-insensitive, potassium-dependent i.p.s.p.s with times to peak of 150-250 ms (long(l)-i.p.s.p.s). 2. The effects of baclofen were investigated on seventy-one neurones. Baclofen was applied by ionophoresis or pressure ejection from micropipettes or was added to the superfusion medium. 3. Baclofen depressed stimulation-evoked e.p.s.p.s in fifty-seven of the sixty neurones tested. This effect was associated with an increase in the stimulation intensity required to produce a synaptically evoked action potential for thirty-nine of forty-four neurones. 4. Baclofen depressed f-i.p.s.p.s in thirty-seven of the thirty-nine neurones tested and l-i.p.s.p.s in each one of the seventeen neurones tested. Reversal potential values for each type of i.p.s.p. were not changed by baclofen and its depressions of each were independent of membrane potential (Em). Baclofen reduced the magnitude and the duration of the conductance increases that were associated with f- and l-i.p.s.p.s. 5. Baclofen hyperpolarized forty of seventy-one neurones and produced outward currents in three of four neurones recorded in voltage clamp at holding potentials between -55 and -65 mV. These actions were associated with 10-58% reductions of neuronal input resistance (RN) and 10-20% increases in neuronal input conductance (gN), respectively. Baclofen decreased the direct excitability of twenty-three of twenty-seven neurones tested. Determinations of the reversal potential for baclofen-induced changes of Em indicate that baclofen increases the conductance of rat neocortical neurones to potassium ions. 6. The EC50 for each action of DL-baclofen was approximately 1 microM. L-Baclofen was greater than 100 times more potent than D-baclofen. 7. Concentrations of bicuculline that blocked f-i.p.s.p.s and responses to ionophoretically applied gamma-aminobutyric acid (GABA) had no effect on the depressions of e.p.s.p.s or the hyperpolarizations and decreases in RN that baclofen produced. 8. Baclofen did not reduce the duration of action potentials that were prolonged with intracellular injections of caesium ions or by superfusions with medium that contained 10 mM-tetraethylammonium (TEA).

Intracellular recordings were obtained from rat neocortical neurons in vitro. The current-voltage-relationship of the neuronal membrane was investigated using current- and single-electrode-voltage-clamp techniques. Within the potential range up to 25 mV positive to the resting membrane potential (RMP: –75 to –80 mV) the steady state slope resistance increased with depolarization (i.e. steady state inward rectification in depolarizing direction). Replacement of extracellular NaCl with an equimolar amount of choline chloride resulted in the conversion of the steady state inward rectification to an outward rectification, suggesting the presence of a voltage-dependent, persistent sodium current which generated the steady state inward rectification of these neurons. Intracellularly injected outward current pulses with just subthreshold intensities elicited a transient depolarizing potential which invariably triggered the first action potential upon an increase in current strength. Single-electrode-voltage-clamp measurements reveled that this depolarizing potential was produced by a transient calcium current activated at membrane potentials 15–20 mV positive to the RMP and that this current was responsible for the time-dependent increase in the magnitude of the inward rectification in depolarizing direction in rat neocortical neurons. It may be that, together with the persistent sodium current, this calcium current regulates the excitability of these neurons via the adjustment of the action potential threshold.

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6091/1/6091.pdf Stangl, E.; Ritter, D.; Gerbes, Alexander L.; Arendt, Rainer M. ddc:610, Medizin

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6152/1/6152.pdf Berghaus, Alexander ddc:610, Medizin

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6200/1/6200.pdf Streffer, C.; Oberhausen, E.; Landfermann, H.-H.; Kellerer, Albrecht M.; Jacobi, W.; Hardt, H. J.; Harder, D.; GumPrecht, D.; Bonka, H.; Aurand, K.; Kaul, A. ddc:610, Med

The findings of Hill et al. (1984) on the greatly enhanced transformation frequencies at very low dose rates of fission neutrons induced us to perform an analogous study with -particles at comparable dose rates. Transformation frequencies were determined with γ-rays at high dose rate (0·5 Gy/min), and with -particles at high (0·2 Gy/min) and at low dose rates (0·83-2·5 mGy/min) in the C3H 10T1/2 cell system. α-particles were substantially more effective than γ-rays, both for cell inactivation and for neoplastic transformation at high and low dose rates. The relative biological effectiveness (RBE) for cell inactivation and for neoplastic transformation was of similar magnitude, and ranged from about 3 at an -particle dose of 2 Gy to values of the order of 10 at 0·25 Gy. In contrast to the experiments of Hill et al. (1984) with fission neutrons, no increased transformation frequencies were observed when the -particle dose was protracted over several hours.

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6218/1/6218.pdf Berghaus, Alexander ddc:610, Medizin

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6220/1/6220.pdf Berghaus, Alexander ddc:610, Medizin

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6222/1/6222.pdf Berghaus, Alexander

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6238/1/6238.pdf Kellerer, Albrecht M. ddc:610, Medizin

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6239/1/6239.pdf Kellerer, Albrecht M. ddc:610, Medizin

A case where the severe course of an orbital phlegmon led to a functionally and cosmetically poor condition is presented. Thirty-five years later, it was possible to achieve a satisfactory result through several operations performed with interdisciplinary cooperation. The orbit and forehead were reconstructed with porous polyethylene, thus ensuring a cosmetically good result. In two operations, the left eye was freed from its upward fixation through cicatrectomy and mobilization of the mucles, so that the eyes were straight again in the primary position. There is a limited binocular visual field. Binocular vision could be restored again after an interruption of 35 years.

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6256/1/6256.pdf Loeffler, M.; Berghaus, Alexander; Berger, Th.; Römer, T. ddc:610, Medizin

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6312/1/6312.pdf Kellerer, Albrecht M. ddc:610, Medizin

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6313/1/6313.pdf Kellerer, Albrecht M.

The mechanism leading to hyperlipidemia in the nephrotic syndrome is not fully understood but may be related in part to loss of high density lipoproteins in the urine of patients with nephrosis. To prove this hypothesis, we compared serum lipoprotein profiles with the excretion of high density lipoproteins in urine in 19 nephrotic patients. Serum cholesterol ranged from 19–152 (median value 45) mg/dl in very low density lipoproteins (VLDL), from 130–443 (median 186) mg/dl in low density lipoproteins (LDL) and from 19–64 (median 33) mg/dl in high density lipoproteins (HDL). Hyperlipoproteinemia was found in 17 patients, which was classified as phenotype IIa (Fredrickson) in 2, as phenotype IIb in 9 and as phenotype IV in 6 subjects. Two patients showed normal lipoprotein patterns. VLDL- and LDL-cholesterol were not found in detectable amounts in urine, whereas HDL-cholesterol was measured in low concentrations from 0.1–8.3 mg/24 h in all samples. There was no correlation between serum HDL-cholesterol and urinary HDL-cholesterol, but a positive correlation between serum LDL-cholesterol and urinary HDL-cholesterol (r= +0.54, p < 0.05). However, the total amount of the daily urinary loss of HDL (

The murine immediate-early (IE) protein pp89 is a nonstructural virus- encoded phosphoprotein residing in the nucleus of infected cells, where it acts as transcriptional activator. Frequency analysis has shown that in BALB/c mice the majority of virus-specific CTL recognize IE antigens. The present study was performed to assess whether pp89 causes membrane antigen expression detected by IE-specific CTL. Site-directed mutagenesis has been used to delete the introns from gene ieI, encoding pp89, for subsequent integration of the continuous coding sequence into the vaccinia virus genome. After infection with the vaccinia recombinant, the authentic pp89 was expressed in cells that became susceptible to lysis by an IE-specific CTL clone. Priming of mice with the vaccinia recombinant sensitized polyclonal CTL that recognized MCMV- infected cells and transfected cells expressing pp89. Thus, a herpesviral IE polypeptide with essential function in viral transcriptional regulation can also serve as a dominant antigen for the specific CTL response of the host.

We have constructed target cells by cotransfection of the MHC gene Ld and fragments of murine cytomegalovirus (MCMV) DNA coding for nonstructural immediate-early (IE) proteins. Transfectants were tested by using CTL clone IE1 with specificity for an IE epitope presented in association with Ld. Data show that clone IE1 recognizes a product of the ie1 transcription unit of MCMV, and that its specificity is shared by approximately 25% of polyclonal IE-specific CTL. The results provide the first definite evidence that expression of a herpes virus IE gene encoding a regulatory protein gives rise to antigen expression detectable by specific CTL

We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that in vivo application of recombinant human IL-2 (rhIL-2) can enhance the antiviral effect of a limited number of CD8+T lymphocytes, not only in prophylaxis, but also in therapy, when virus has already colonized host tissues. The observed net effect of IL-2 was consistent with the assumption of daily effector population doublings. The prospects for IL-2-supported immunotherapy of established CMV infection depend upon the tissues involved in disease. It appears that the prospects for controlling established CMV adrenalitis are less promising than for a therapy of interstitial CMV pneumonia.

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6651/1/6651.pdf Jüngst, Dieter; Zachoval, R.

We have shown in a murine model system for acute, lethal cytomegalovirus (CMV) disease in the immunocompromised natural host that control of virus multiplication in tissues, protection from virus-caused tissue destruction, and survival are mediated by virus-specific CD8+ CD4-T lymphocytes. Protection from a lethal course of disease did not result in a rapid establishment of virus latency, but led to a long-lasting, persistent state of infection. The CD8- CD4+ subset of T lymphocytes was not effective by itself in controlling murine CMV (MCMV) multiplication in tissue or essential for the protective function of the CD8+ CD4- effector cells. The antiviral efficacy of the purified CD8+ CD4- subset was not impaired by preincubation with fibroblasts that presented viral structural antigens, but was significantly reduced after depletion of effector cells specific for the nonstructural immediate-early antigens of MCMV, which are specified by the first among a multitude of viral genes expressed during MCMV replication in permissive cells. Thus, MCMV disease provides the first example of a role for nonstructural herpesvirus immediate-early antigens in protective immunity.

To confirm that immediate-early (IE) genes of murine cytomegalovirus (MCMV) give rise to antigens recognized by specific cytolytic T lymphocytes (CTL), a 10.8-kilobase fragment of MCMV DNA which is abundantly transcribed at IE times was transfected into L cells expressing the Ld class I major histocompatibility glycoprotein. The viral genome fragment contains sequences of the three IE transcription units of MCMV: ie1, ie2, and ie3. In the transfected cell lines, only the predominant 2.75-kilobase transcript of ie1 and its translation product pp89 could be detected. The transfectants were analyzed for membrane expression of an IE antigen by employing clone IE1, an IE-specific CTL clone, as the probe. Only cells that expressed both the MCMV IE gene(s) and the Ld gene were recognized by the CTL clone.

In murine cytomegalovirus, abundant immediate-early transcription originates from 0.769 to 0.815 map units of the genome. This region contains the immediate-early gene (gene ieI) which encodes pp89, a phosphoprotein active in transcriptional regulation. In this paper we report on the precise location, structural organization, and sequence of gene ieI. The predominant ieI transcript, a 2.75-kilobase mRNA, is generated by splicing and composed of four exons. The precise termini of the 2.75-kilobase mRNA and the positions of the exons were determined by nuclease digestion experiments with either 5' or 3' end-labeled DNA fragments or in vitro transcribed cRNA probes. Exons of 300, 111, 191, and 1,703 nucleotides are separated by introns of 825, 95, and 122 nucleotides. The first AUG is located in the second exon of 111 nucleotides, and a single open reading frame of 1,785 nucleotides predicts a protein of 595 amino acids with a calculated molecular weight of 66,713. The N-terminal region of the protein contains sequences similar to a consensus sequence of histone 2B proteins. The regulatory function of pp89 and the role of this protein as an immunodominant antigen are discussed in relation to the amino acid sequence.

Cloned genomic fragments from the region (0.769 to 0.818 map units) coding for immediate-early (IE) transcripts of murine cytomegalovirus (MCMV) were used to analyze the physical organization of this region, the direction of transcription, and the proteins synthesized in vitro. Three IE transcription units could be identified. From IE coding region 1 (ie1; 0.781 to 0.796 map units) a dominant 2.75-kilobase (kb) RNA was transcribed from right to left on the prototype arrangement of the MCMV genome which directed the synthesis of an 89,000-molecular-weight polypeptide (89K polypeptide), the major IE protein. This phosphoprotein (pp89) has been shown to be active in the regulation of transcription. Upstream of ie1 and separated by the MCMV enhancer sequence was a second IE coding region, ie2, which was mapped at 0.803 to 0.817 map units. From ie2 a 1.75-kb RNA of moderate abundance was transcribed in the direction opposite to that of the ie1 RNA. After hybrid selection of the ie2 transcript, a 43,000-molecular-weight translation product was detected. A third coding region, ie3, was located directly downstream of ie1 (0.773 to 0.781 map units). The series of RNAs with low abundance, terminating in ie3, probably used the ie1 transcription start site and ranged from 1.0 to 5.1 kb in size. The 5.1-kb RNA apparently represents the nonspliced transcript from both coding regions ie1 and ie3. A 15K polypeptide was translated in vitro from RNA that was hybrid selected by ie3 sequences. Immunoprecipitation with monoclonal antibody revealed that 31K to 67K polypeptides were related to pp89. Some of these proteins were translated from RNAs that were smaller than 2.75 kb. Polypeptides related to pp89 were also synthesized in vivo. Because polypeptides unrelated to pp89 that were translated from RNA that was selected by ie2 and ie3 sequences were not immunoprecipitated by murine antisera, we assumed that the amount of these proteins synthesized in vivo during infection was probably very low

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6658/1/6658.pdf Jüngst, Dieter; zur Nieden, J.; Ritter, M. M. ddc:610

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6663/1/6663.pdf Paumgartner, Gustav; Jüngst, Dieter; Ritter, M. M. ddc:6

The existence of four subpopulations in resting porcine T lymphocytes is documented. In addition to the two known subpopulations which are typified by a mutually exclusive expression of either the CD8 or the CD4 differentiation antigen, CD4-CD8+ and CD4+CD8- T lymphocytes, respectively, two unusual subpopulations were prominent not only in peripheral blood, but also in lymphoid tissues: CD4-CD8- T lymphocytes expressing neither of these antigens and CD4+CD8+ T lymphocytes coexpressing both antigens. While CD4+CD8+ lymphoblasts have been found also in other species, resting T lymphocytes with that phenotype are without precedent among all species analyzed to date. This unique composition of the porcine T lymphocyte population has to be taken into consideration when the swine is used as a large animal model in experimental medicine.

The expression of an antigen on porcine T lymphocytes detected by murine monoclonal antibody (mAb) 8/1 was investigated by functional studies and dual-parameter immunofluorescence. mAb 8/1 reacts with greater than 95% of thymocytes and in peripheral blood with all T lymphocytes and with cells of the monocyte/macrophage lineage, but not with B cells, erythrocytes, and platelets. Pretreatment of peripheral blood lymphocytes with mAb 8/1 plus complement abrogated the proliferative response in vitro to mitogen, soluble antigen, and MHC determinants. Dual-parameter immunofluorescence revealed that resting porcine T8+ as well as T4+ lymphocytes express the 8/1 antigen, whereas after in vitro activation, cell surface expression of the antigen was low or absent in both T cell subsets. Thus, the 8/1 antigen represents a marker that discriminates between resting and activated T lymphocytes. Distribution and functional criteria indicate that 8/1 represents a novel marker not described before for any other mammalian species.

Thu, 1 Jan 1987 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6768/1/6768.pdf Koszinowski, Ulrich H.; Jonjic, Stipan; Bühring, Hans-Jörg; Weiland, Frank; Zawatzky, R.; Reddehase, Matthias J.

The distribution of the functional subsets of porcine T cells, the cytolytic/suppressor (Tc/s) and the helper/inducer (Th/i) cells was studied in cryostat sections of thymus, lymph nodes, tonsils, Peyer's patches, spleen and liver using the indirect immunoperoxidase technique. Three murine monoclonal antibodies (mAb) were used. The mAb 8/1 reacts with an antigen present on all T cells and on cells of the myeloid lineage; the antigen has not yet been characterized biochemically. The mAb 295/33 (anti-T8) binds to the porcine T8 antigen and defines the Tc/s subset, while mAb PT-4 (anti-T4) detects the porcine T4 antigen and defines the Th/i subset. Practically all thymocytes were stained by mAb 8/1. The majority of cortical thymocytes apparently co-expressed T8 and T4, whereas distinct fractions of medullary cells were labelled by either anti-T8 or anti-T4. In peripheral lymphoid organs all three mAb reacted with cells in the thymus-dependent areas and with cells scattered in the lymphoid follicles. In lymph nodes, tonsils and Peyer's patches, anti-T8 and anti-T4 each labelled approximately half of the cells stained by mAb 8/1. In the periarteriolar lymphoid sheath of the spleen, anti-T4 labelled more cells than did anti-T8. The reactivity of mAb 8/1 with the Kupffer cells of the liver demonstrated the expression of the 8/1 antigen on cells of the monocyte lineage. The T8 and T4 antigens could not be detected in acetone-fixed and paraffin-embedded sections, while the antigen recognized by mAb 8/1 remained preserved. Altogether, despite an inverted microanatomical structure of porcine lymph nodes, the frequency and distribution of T8+ and T4+ cells in thymus-dependent areas proved to be similar to those found in other species.

Transport of cytoplasmically synthesized precursor proteins into or across the inner mitochondrial membrane requires a mitochondrial membrane potential. We have studied whether additional energy sources are also necessary for protein translocation. Reticulocyte lysate (containing radiolabelled precursor proteins) and mitochondria were depleted of ATP by pre-incubation with apyrase. A membrane potential was then established by the addition of substrates of the electron transport chain. Oligomycin was included to prevent dissipation of Δψ by the action of the F0F1-ATPase. Under these conditions, import of subunit β of F1-ATPase (F1β) was inhibited. Addition of ATP or GTP restored import. When the membrane potential was destroyed, however, the import of F1β was completely inhibited even in the presence of ATP. We therefore conclude that the import of F1β depends on both nucleoside triphosphates and a membrane potential.

Mon, 1 Dec 1986 12:00:00 +0100 https://epub.ub.uni-muenchen.de/5384/1/Zimmermann_Wolfgang_5384.pdf Zimmermann, Wolfgang; Heinrich, Peter C.; Northemann, Wolfgang; Heising, Michael; Kodelja, Vitam

Wed, 1 Jan 1986 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7290/1/7290.pdf Bohmert, H.; Schwandt, P.; Riel, K. A.; Richter, W. O.; Baumeister, Rüdiger ddc:610,

Wed, 1 Jan 1986 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7291/1/spaetergebnisse_der_reduktionsplastik_nach_mckissock_7291.pdf Bohmert, H.; Umlandt, A.; Daigeler, R.; Baumeister, Rüdiger ddc:610, Medizin

Wed, 1 Jan 1986 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7330/1/7330.pdf Kynast, G.; Berlit, Peter; Krause, Klaus-Henning ddc:610, Medizin

Wed, 1 Jan 1986 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7334/1/7334.pdf Scheglmann, K.; Rittmann, M.; Brosi, K.; Krause, Klaus-Henning ddc:610, Medizin

In a retrospective study the reports of 211 cases of cardiogenic cerebral embolism - diagnosed on the base of neurological and cardiological findings - were analyzed in view of signs and findings of prognostic value. There were 21 patients with TIA, 39 cases of RIND and 151 patients with cerebral infarction, 60 of which showed mild and 91 severe neurological symptoms. 38 patients died during the period of hospitalization. While sex of the patients as well as vascular risk factors (hypertension, diabetes mellitus, cigarette smoking) did not influence the clinical course of the disease, patients with TIA or RIND in general were younger (about 5 years) than those with severe stroke. Prognosis of cardiogenic cerebral embolism depended to a great degree on the underlying heart disease. Cerebral embolism after myocardial infarction showed a better remission of symptoms than embolism in atrial fibrillation. In the group of valvular diseases the course of embolic strokes in mitral lesions was worse than in aortal valve disease. Prognosis was worst in endocarditis, both in view of neurological deficit and of mortality. Mostly, the cardiogenic emboli lead to infarctions of the middle cerebral artery territory (78 per cent) with a predilection for the left hemisphere. In media-syndromes the clinical course was significantly worse in patients with additional homonymous visual defect compared to incomplete infarctions. Initial disturbance of conscience reduced prognosis quoad vitam et restitutionem significantly. Of the neuroradiological findings, the detection of arterial occlusion or circulatory disturbance in angiography as well as the finding of an ischemic lesion in computed axial tomography (CAT) was correlated with a severe course of the embolic stroke. While 7 patients with hemorrhagic infarction in CAT-Scan showed no differences in the clinical course, the 14 patients with pathological cerebral spinal fluid findings in embolism had an unfavourable prognosis. The development of epileptic seizures did not influence the further course of the infarction to a significant extent. Results are compared with the current world literature.

Eine seltene Ursache der primären Nebennierenrindeninsuffizienz ist die X-chromosomal vererbte Adrenomyeloneuropathie. Neurologisch ist sie durch Zeichen der zentralen und peripheren Demyelinisierung, endokrinologisch durch einen M. Addison und eine zusätzliche primäre Hodeninsuffizienz gekennzeichnet. Bei zwei Patienten mit diesem Krankheitsbild konnte der Stoffwechseldefekt im Abbau langkettiger Fettsäuren durch Bestimmung eines erhöhten Hexakosansäure-Spiegels (C 26) im Blut gesichert werden. Bei einem Patienten (Fall 1) lag ein isolierter Ausfall der Zona fasciculata vor, beim anderen (Fall 2) fand sich eine klinisch manifeste komplette Nebennierenrindeninsuffizienz. Beide Patienten haben einen beginnenden Hypogonadismus. Die neurologische Symptomatik ging im Fall 2 der Entwicklung der endokrinen Ausfälle voraus, im Fall 1 führten Familienanamnese und Nebennierenrindeninsuffizienz zur Diagnosestellung. Beim Nachweis einer peripheren Neuropathie bei männlichen Jugendlichen oder jüngeren Erwachsenen sollte auf die Zeichen einer beginnenden Nebennierenrindeninsuffizienz geachtet werden.

The Fe/S protein of complex III is encoded by a nuclear gene, synthesized in the cytoplasm as a precursor with a 32 residue amino-terminal extension, and transported to the outer surface of the inner mitochondrial membrane. Our data suggest the following transport pathway. First, the precursor is translocated via translocation contact sites into the matrix. There, cleavage to an intermediate containing an eight residue extension occurs. The intermediate is then redirected across the inner membrane, processed to the mature subunit, and assembled into complex III. We suggest that the folding and membrane-translocation pathway in the endosymbiotic ancestor of mitochondria has been conserved during evolution of eukaryotic cells; transfer of the gene for Fe/S protein to the nucleus has led to addition of the presequence, which routes the precursor back to its “ancestral” assembly pathway.

Wed, 1 Jan 1986 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7529/1/Peter_becker_7529.pdf Boshart, Michael; Becker, Peter B.; Strähle, Uwe; Gloss, Bernd; Danesch, U.; Schmid, Wolfgang; Schütz, Günther

Bei elf von 43 nichtimmunen Patienten mit Malaria tropica traten eine oder mehrere Organkomplikationen auf: zerebrale Malaria, akute respiratorische Insuffizienz, akutes Nierenversagen, Sekundärinfektion, Autoimmunhämolyse, spontane Milzruptur und akute Pankreatitis. Die Parasitämie betrug 0,1 bis 60 %. Initiale antiparasitäre Therapie mit Chinin parenteral führte in neun Fällen zu rascher Rückbildung der Parasitämie. Zusätzlich wurde ein zweites schizontozides Mittel entsprechend der Resistenzlage gegeben. Die supportive Therapie umfaßte intensivmedizinische Überwachung mit Bilanzierung von Elektrolyt- und Wasserhaushalt sowie gegebenenfalls eine frühzeitige Hämodialyse und (oder) endotracheale Intubation mit PEEP-Beatmung. In einem Fall mit exzessiver Parasitämie wurde eine Austauschtransfusion durchgeführt. Heparin wurde nur bei nachgewiesener disseminierter intravasaler Gerinnung gegeben, Corticosteroide nur bei persistierender Autoimmunhämolyse. Alle Patienten überlebten ohne zurückbleibende Defekte. Die retrospektive Analyse zeigt, daß neben einer raschen spezifischen Therapie die supportive Behandlung der einzelnen Organkomplikationen für Verlauf und Prognose der komplizierten Malaria tropica mitentscheidend ist.