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Biomedical subjects

H Baumann

Publications and source records attributed to H Baumann.

At least 163 records · Page 9Linked to original sources

Peptide diazomethyl ketones are inhibitors of subtilisin-type serine proteases.

Peptide diazomethyl ketones, well known as specific cysteine protease inhibitors are also potent inhibitors of the microbial serine proteases thermitase (EC 3.4.21.14) and subtilisin Carlsberg (EC 3.4.21.14). The affinity of the enzymes towards the synthetic inhibitors Z-Ala(n)-PheCHN2 (n = 0, 1, 2) depends on the chain length and is in the same range as for the corresponding chloromethyl ketones. Both kinds of inhibitors react irreversibly in a 1:1 ratio with the enzymes and covalently bind to the active site histidine of both subtilisin Carlsberg and thermitase despite the fact that thermitase contains an active-site cysteinyl residue. The mechanism of the inhibition reaction is discussed.

Amino Acid Sequence↗

The acute-phase protein response in parasite infection. Nippostrongylus brasiliensis and Trichinella spiralis in the rat.

During acute inflammation, the mammalian liver responds with increased production and secretion of a series of plasma glycoproteins, collectively termed the acute-phase proteins, resulting from the release at the site of inflammation of polypeptide cytokines, including IL-1 and IL-6, which interact with receptors on hepatocytes and alter gene expression. This attribute of the systemic acute-phase response was studied throughout the course of infection with two nematode parasites in rats. Significant increases in serum haptoglobin, alpha 1-acid glycoprotein and alpha 1-cysteine protease inhibitor were detected coincident with episodes of skin, lung and intestinal pathology during Nippostrongylus brasiliensis, but were not seen during Trichinella spiralis, infection of the rat despite similar intestinal pathology. These changes were seen at both the protein and mRNA levels in the liver. Infection with T. spiralis was not anti-inflammatory, as macrophages from various sites could be induced in vitro to release inflammatory cytokines, and in vivo induction of inflammation by turpentine injection was similar in control and infected animals. However, macrophage populations recovered from animals infected with T. spiralis were not activated. Moreover, intestinal infection alone with intestinal stages of N. brasiliensis also failed to elicit the systemic acute-phase protein response, requiring an explanation involving skin and lung for the acute-phase response during gut inflammation in a primary infection with N. brasiliensis. Taken together, these data suggest that during the intestinal phase of nematode infection, with pathological changes to the gut, the systemic acute-phase response is not elicited through compromise or lack of stimulation of inflammatory cells in the intestine. The systemic parameters of the acute-phase response may not be a component of gastrointestinal pathology.

Acute-Phase Proteins↗

Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulating factors and other mediators of inflammation.

The hepatic response to systemic injury is characterized by a co-ordinated increase in the expression of several, functionally essential plasma proteins. The factors responsible for initial hepatic stimulation have been identified and include the cytokines IL-1 (interleukin-1), tumor necrosis factor alpha (TNF alpha), IL-6 (interleukin-6), hepatocyte-stimulating factor-III (HSF-III) as well as corticosteroids. The absolute level of expression of the regulated proteins appears to be modulated by the pre-existing hepatic hormonal environment and changes to that environment that occur during acute phase reactions. The specific effects of glucocorticoids, IL-1 and activation of protein kinase C are addressed in this study. In order to predict the phenotype of liver response in acute phase, the hepatic activities of all inflammatory cytokines present must be established. Moreover, it must be recognized that the hepatic environment itself can modulate the anabolic response of the liver to these cytokines. The same considerations are needed when determining the changes seen during the progression to chronic inflammation.

Acute-Phase Proteins↗

[Hydrops fetalis in tachycardia: diagnostic and therapeutic procedures].

We report on a 33-year-old para II who was admitted to our hospital in her 29th gestational week with extensive fetal hydrops. Examinations showed a fetal supraventricular tachycardia with biventrical cardiac insufficiency. Digoxin was given both to the mother and to the fetus. At first, this treatment seemed to have no effect. Over a period of several weeks, however, oral therapy with digoxin and verapamil resulted in a stabilized fetal heart rate (175-180 beats/min). Signs of fetal cardiac insufficiency disappeared almost completely. In the 39th week the child was born spontaneously. Clinical examination revealed only a slight cardiac insufficiency. New possibilities of intrauterine therapy are discussed in the light of this case and other reports in the literature.

Adult↗

Effect of epidural anesthesia for cesarean delivery on maternal femoral arterial and venous, uteroplacental, and umbilical blood flow velocities and waveforms.

The effect of epidural anesthesia on the maternal femoral arterial and venous, uteroplacental, and umbilical circulations was studied by the pulsed Doppler technique in 13 women undergoing elective cesarean delivery. Resistance and pulsatility indices of umbilical arterial velocity waveforms did not change with the use of epidural anesthesia. In the uteroplacental circulation, these indices increased in 11 patients, suggesting an increase in resistance. Reduction of sympathetic tone in resistance and capacitance vessels was reflected in the femoral artery by an increase in systolic and end-diastolic velocities, a reversal of the post-systolic backward flow, and an increase in mean velocity. The latter also occurred in the femoral vein. The diameters of these large maternal vessels did not change. This study suggests an impairment in uteroplacental circulation associated with a drop in peripheral vascular resistance and an increase in leg blood flow after epidural anesthesia.

Anesthesia, Epidural↗

Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor.

The coordinate increase in the hepatic production of the acute phase plasma proteins appears to be mediated by several cytokines produced by different cell types. One factor, hepatocyte-stimulating factor III (HSF-III), constitutively produced by human squamous carcinoma (COLO-16) cells, stimulates the synthesis of the same set of acute phase plasma proteins as the structurally distinct IL-6. The physicochemical properties of HSF-III coincide with those of the T cell-derived leukemia-inhibitory factor (LIF). Human rLIF, tested on hepatoma cells, indicated a liver-regulating activity identical to HSF-III. The LIF activity is specifically neutralized by HSF-III antibodies. COLO-16 cells contain an LIF mRNA which is characteristic for lectin-stimulated T cells, suggesting that HSF-III is an epidermal cell-derived form of LIF. This result provides additional evidence for the close relationship between acute phase regulation of the liver and control of proliferation and differentiation of hemopoietic cells by identical cytokines.

Acute-Phase Proteins↗

Human hepatocyte-stimulating factor-III and interleukin-6 are structurally and immunologically distinct but regulate the production of the same acute phase plasma proteins.

Human squamous carcinoma (COLO-16) cells synthesize and secrete hepatocyte-stimulating factor-III (HSF-III), a glycoprotein with Mr = 39,000, which stimulates the synthesis of several acute phase plasma proteins in human hepatoma (HepG2) cells. The qualitative response of HepG2 cells to HSF-III is essentially the same as that elicited by human recombinant interleukin-6 (IL-6). Although similar in hepatocyte-stimulating activity, HSF-III and IL-6 are distinct molecules which differ not only in size and charge but also in immunologic properties: no cross-recognition of HSF-III and IL-6 occurs using neutralizing antibodies against IL-6 and HSF-III, respectively. In addition, Northern blot hybridization of IL-6 cDNA to mRNA from COLO-16 cells revealed no detectable IL-6 message. HSF-III does not compete for binding to the IL-6 receptors suggesting that HepG2 cells carry receptors specific for each hormone. Both receptor types may trigger similar intracellular processes explaining the identical regulation of acute phase protein expression.

Acute-Phase Proteins↗

IL-6 modulates the synthesis of a specific set of acute phase plasma proteins in vivo.

Human rIL-6, produced either in COS cells or Escherichia coli, similarly stimulates the production of acute phase plasma proteins in cultured human and rat hepatoma cells. This anabolic effect in hepatoma cells suggested a potential in vivo role of the cytokine in mediating the hepatic response to inflammation. Injection of IL-6 into adult male rats elicited a cytokine-specific change in the liver expression of acute phase proteins. As predicted from in vitro studies, glucocorticoids were needed to achieve a maximal IL-6 response in vivo. Optimal conditions were found to be two i.p. injections of 35 to 120 micrograms IL-6 and 65 micrograms dexamethasone per kg body weight administered at 12-h intervals. Within 24 h, the plasma concentrations for alpha 2-macroglobulin, fibrinogen, thiostatin, and hemopexin were increased to levels approximating those observed in acute phase animals. These results support the notion that direct interaction of IL-6 with the liver is an essential part in initiating the hepatic acute phase reaction.

Acute-Phase Proteins↗

Interleukin-1 and interleukin-6 stimulate acute-phase protein production in primary mouse hepatocytes.

Primary mouse hepatocytes were treated with the acute-phase mediators interleukin-1, interleukin-6, and glucocorticoids, singularly and in combination, in order to delineate the spectrum of proteins induced by the stimulatory factors. As found for rat and human liver cells, mouse hepatocytes responded to the cytokines by increasing production of acute-phase proteins, which in mice include haptoglobin, alpha 1-acid glycoprotein, complement C-3, serum amyloid A, and hemopexin. Serum amyloid A was unusual in that only the acidic peptide form responded to treatment with IL-1 and IL-6; the more basic form remained unchanged. In addition, an unidentified secretory protein was induced only by mixtures containing IL-6. The present study shows that a combination of IL-1, IL-6, and glucocorticoids is required for regulation of acute-phase plasma protein production in mouse liver cells.

Acute-Phase Proteins↗

Surgical treatment of myeloradiculopathy in cervical spondylosis. A report on 438 operations.

In the past eleven years we have performed 438 microsurgical ventral discectomies with bilateral foraminotomy followed by fusion with palacos in the cervical spine in our clinic. An analysis of the preoperative symptoms shows a great variability and overlapping of the various segments. To determine the right level for the operation it is crucial that the results of the clinical and the radiological examinations be evaluated. The results of ascending myelography and CT scans are of great value. In cases of cervical myelopathy a multisegmental operation is often necessary to obtain good results. The complication rate was small in our patients and a second operation was only necessary in a few cases. We had very good postoperative results in radicular pain and muscle weakness. In patients with symptoms of cervical myelopathy we achieved considerable improvement.

Cervical Vertebrae↗

Determination of the minimum number of cardiac cycles necessary to ensure representative blood flow velocity measurements.

The aim of this study was to determine the minimum number of cardiac cycles necessary over which blood flow velocity representative of the situation (and not unduly influenced by sporadic irregularities). Blood flow was measured by Doppler ultrasound in the adult a. carotis communis, a. femoralis and fetal a. umbilicalis. The coefficients of variation (CV) for the Pulsatility Index (PI), Resistance Index (RI) and Time Average of Space Average Velocities (TASAV) from 10 averaged cycles were compared with the CVs of the respective indices from 2, 3, 4 up to 9 averaged cycles. The number of averaged cycles where the difference between the coefficients of variability became insignificant (Wilcoxon signed rank test) was taken to be the point at which representative values of PI, RI or, respectively, TASAV are assured. For PI evaluation for the a. carotis communis with either the 7 mx or 15 mx calculation program one needs to average over 7 cardiac cycles. Manually determining the maximum frequency curve envelope, 5 cycles are sufficient. Using these same calculation programs for the a. femoralis, 5, 6 and, respectively, 6, cycles are sufficient for representative PI indices; for the umbilical artery, 6, 8 and, respectively, 7 cycles are necessary. For RI, 5 cycles are sufficient in both the a. carotis communis and a. umbilicalis by manual evaluation. For TASAV, a minimum of 3 cycles for the a. carotis communis and of 7 for the a. femoralis are necessary. Thus the number of cardiac cycles which should be averaged is dependent on the vessel being examined, the index being calculated, and the program being used.

Blood Flow Velocity↗

Doppler sonographic evaluation of exercise-induced blood flow velocity and waveform changes in fetal, uteroplacental and large maternal vessels in pregnant women.

The aim of this study was the evaluation by Doppler sonography of blood flow velocity and waveforms in maternal (Femoral artery and vein, carotid artery, uteroplacental) and fetal (Umbilical artery) vessels before and after exercise. Thirteen healthy women with uncomplicated pregnancies (and outcomes) participated in the study between the 36th and 40th gestational week. Each proband underwent 5 exercise tests in a sitting position on a bicycle ergometer with a work load of 100 Watts during 3 minutes. The Doppler measurements were performed with Acuson 128. In the femoral and carotid arteries, peak velocities (systolic and end-diastolic, and for the femoral artery also post-systolic) as well as the mean blood flow velocities were measured. Mean blood flow velocity was also measured in the femoral vein. For the measurements of the arterial diameters, the M-Mode technique, for the femoral vein diameter, the B-Mode technique was used. The uteroplacental and umbilical blood flow waveforms were analysed by the Resistance and Pulsatility Indices. The maternal heart rate as well as systolic and diastolic blood pressures increased after each of the exercise tests. The mean blood flow velocity increased in both the femoral artery and vein while the vessel diameter remained constant. In the carotid artery, however, the velocity remained constant. An analysis of the velocity waveforms for the femoral artery showed in increase in the systolic and end-diastolic velocities as well as a reversal of the post-systolic flow, where the velocity is negative in a state of rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Adaptation of contractile proteins in human heart and skeletal muscles.

Sarcomeric muscles including the myocardium respond to increased workload with adaptation by differential gene expression and without cell division. This is characteristic for postmitotic tissues. We showed that a short period of high intensity endurance training induces a shift from fast myosin heavy (HC) and light (LC) chain isoforms towards the slow variety within histochemically typed fibres of human vastus lateralis muscle. In an intermediary state of transition both varieties of isoforms are co-expressed in one fibre. Likewise a shift from the fast myosin alpha-HC towards the slow beta-HC was observed in the atria of severely insufficient human hearts. Such a shift does not occur in the ventricular myocardium where the beta-isoform is expressed mainly. However, both ventricular myosin LC species do occur in the atrium while only the atrial LC-1 isoform appears in the ventricular muscle under increased workload. The expression of the myosin HC and LC isoforms is regulated independently of one another and tends to change towards the slow myosin type with its greater contraction economy.

Adult↗