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Biomedical subjects

G Fuchs

Publications and source records attributed to G Fuchs.

At least 55 records · Page 3Linked to original sources

Autotrophic synthesis of activated acetic acid from CO2 in Methanobacterium thermoautotrophicum. Synthesis from tetrahydromethanopterin-bound C1 units and carbon monoxide.

The synthesis of acetyl-CoA from CO2, H2, and various C1 compounds was studied in vitro with extracts and with protein fractions of Methanobacterium thermoautotrophicum. Acetyl-CoA synthesis from CO2 and H2 by extracts required CO2 reduction to CH4 to proceed. Both processes were highly stimulated by formaldehyde which served as the carbon precursor of both CH4 and the CH3 group of acetate. Carbon monoxide in combination with formaldehyde dramatically stimulated the acetyl-CoA synthesis up to 150-fold. In this system, which did not require CO2 reduction to the formaldehyde and CO level, acetyl-CoA synthesis was no longer dependent on CH4 formation. The soluble (100,000 X g supernatant) cell protein was resolved into a protein fraction [45-60% (NH4)2SO4-fraction] which catalyzed acetyl-CoA synthesis at a specific rate of 15 nmol X min-1 X (equivalent of mg cell protein)-1 (60 degrees C). This oxygen-sensitive enzyme reaction required dithioerythritol for activity and was strictly dependent on coenzyme A, CO, and N5,N10-methylene tetrahydromethanopterin, N5-methyl tetrahydromethanopterin or formaldehyde plus tetrahydromethanopterin. The incorporation of formaldehyde is explained by the spontaneous formation of methylene tetrahydromethanopterin. The product of the reaction, acetyl-CoA, was quantitatively derived from CO (carboxyl of acetate) and a C1 derivative of tetrahydromethanopterin (methyl of acetate). The C1 derivative of tetrahydromethanopterin could not be replaced by a C1 derivative of tetrahydrofolate or by methyl-coenzyme M; ATP was not required. The active protein fraction contained CO dehydrogenase and at least on corrinoid protein. These results provide strong biochemical arguments for the proposed mechanism of autotrophic acetyl-CoA synthesis in Methanobacterium.

Acetyl Coenzyme A

Anaerobic degradation of phenol by pure cultures of newly isolated denitrifying pseudomonads.

From various oxic or anoxic habitats several strains of bacteria were isolated which in the absence of molecular oxygen oxidized phenol to CO2 with nitrate as the terminal electron acceptor. All strains grew in defined mineral salts medium; two of them were further characterized. The bacteria were facultatively anaerobic Gram-negative rods; metabolism was strictly oxidative with molecular oxygen, nitrate, or nitrite as electron acceptor. The isolates were tentatively identified as pseudomonads. Besides phenol many other benzene derivatives like cresols or aromatic acids were anaerobically oxidized in the presence of nitrate. While benzoate or 4-hydroxybenzoate was degraded both anaerobically and aerobically, phenol was oxidized under anaerobic conditions only. Reduced alicyclic compounds were not degraded. Preliminary evidence is presented that the first reaction in anaerobic phenol oxidation is phenol carboxylation to 4-hydroxybenzoate.

Anaerobiosis

Purification of alpha-toxin from Staphylococcus aureus and application to cell permeabilization.

Crude alpha-toxin was produced by Staphylococcus aureus, strain Wood 46. The amount of exotoxin was monitored during growth and all subsequent purification steps by determination of its hemolytic activity against rabbit erythrocytes. The culture supernatant was treated with ammonium sulfate (75% saturation). The resulting precipitate was dialyzed and subjected to cation-exchange chromatography. The fractions containing the hemolytic activity were further purified by gel chromatography. The final product was enriched by a factor of 8.5 compared to the crude toxin. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis the purified toxin exhibited one major band. It caused the release of 86Rb+ and ATP from rat insulinoma (RIN A2) as well as pheochromocytoma cells (PC12) in culture, indicating efficient permeabilization of their plasma membranes for small molecules.

Adenosine Triphosphate

Transurethral ultrasonic ureterolithotripsy using a solid-wire probe.

A multicenter study evaluates a new technique for transurethral ultrasonic ureterolithotripsy utilizing a solid-wire probe. The transverse vibrations of the probe cause greater stone disintegration. A small ureteroscope is used and a basket is not required. There was a 96.6 per cent success rate in 118 cases. This technique has significantly improved ultrasonic lithotripsy. It has proved to be useful for upper ureteral stones not amenable to extracorporeal shock-wave lithotripsy and lower ureteral stones including "steinstrasse."

Evaluation Studies as Topic

A clinical study of the selective MAO-A-inhibitor moclobemide (Ro 11-1163): a comparison of 2 different dosages with particular reference to platelet MAO-activity and urinary MHPG-excretion.

A new selective MAO-A-inhibitor (noclobemide) was used in a double-blind comparative study of 23 patients with severe unipolar or bipolar depressive disorder. Two different doses of medication were given for 4 weeks. Effectiveness was measured by improvements in the Hamilton Rating Scale for Depression, a self-rating scale and clinical global impression. Platelet MAO-activity and urinary MHPG-excretion was also determined. Moclobemide proved to be a well-tolerated and effective antidepressant, with both groups showing improvement. Platelet MAO-activity was not markedly influenced by moclobemide, possibly because it selectively inhibits MAO-A. Urinary MHPG did not change significantly with treatment.

Adult

Sodium-dependence of the saturability of carrier-mediated noradrenaline efflux from noradrenergic neurones in the rat vas deferens.

The carrier-mediated transport of 3H-noradrenaline out of noradrenergic neurones was studied in vasa deferentia obtained from rats after pretreatment with reserpine and pargyline (to inhibit vesicular storage and monoamine oxidase, respectively). The tissue was first preincubated with various concentrations of 3H-noradrenaline (0.3--100 mumol/1; 30 min) and then washed out for 110 min with amine-free medium. During the last 10 min of washout, carrier-mediated neuronal efflux of 3H-noradrenaline was elicited by exposure to either Na+-free medium or 100 mumol/l veratridine; it was measured at 1-min intervals. While the peak rates of carrier-mediated 3H-noradrenaline efflux elicited by Na+-free medium were linearly related to the 3H-noradrenaline content of the tissue (which cannot be raised beyond a certain maximal value, since uptake is saturable), those evoked in response to veratridine approached saturation as the 3H-noradrenaline level in the tissue was raised. Hence, saturation of 3H-noradrenaline outward transport was demonstrated at high (exposure to veratridine), but not at low (exposure to Na+-free medium) intraneuronal Na+ concentrations. The results indicate that the Km for the mediated outward transport of noradrenaline across the plasma membrane of noradrenergic neurones is inversely related to the internal Na+ concentration, just as the Km for the mediated inward transport of noradrenaline (i.e., the neuronal noradrenaline uptake) is inversely related to the external Na+ concentration.

Animals

Nomifensine and psychological dependence--a case report.

This case report indicates that nomifensine has not only a specific antidepressant profile but also a dose dependent addictive potential in patients with "addictive problems". Nomifensine supports not only norepinephrine transmission, but also acts on dopamine metabolism and this may be responsible for the stimulation of motor activity. This is in contrast to more frequently used tri- and tetracyclic antidepressants. This case report further supports other observations that several patients have psychological withdrawal difficulties after long term treatment with nomifensine in high doses (400-600 mg).

Adult

Pathogenesis of Shigella diarrhea: rabbit intestinal cell microvillus membrane binding site for Shigella toxin.

This study examined the binding of purified 125I-labeled shigella toxin to rabbit jejunal microvillus membranes (MVMs). Toxin binding was concentration dependent, saturable, reversible, and specifically inhibited by unlabeled toxin. The calculated number of toxin molecules bound at 4 degrees C was 7.9 X 10(10) (3 X 10(10) to 2 X 10(11))/micrograms of MVM protein or 1.2 X 10(6) per enterocyte. Scatchard analysis showed the binding site to be of a single class with an equilibrium association constant, K, of 4.7 X 10(9) M-1 at 4 degrees C. Binding was inversely related to the temperature of incubation. A total of 80% of the labeled toxin binding at 4 degrees C dissociated from MVM when the temperature was raised to 37 degrees C, but reassociated when the temperature was again brought to 4 degrees C. There was no structural or functional change of MVM due to toxin as monitored by electron microscopy or assay of MVM sucrase activity. These studies demonstrate a specific binding site for shigella toxin on rabbit MVMs. The physiological relevance of this receptor remains to be determined.

Animals

Experimental basis of angioinfarction for the treatment of renal hypertension.

Collateral circulation and recanalization represent the main problems of organ-ablating renal embolization. Different animal models were used to study the influence of central, peripheral, and capillary occlusion on organ necrosis. The first laboratory experiments were performed to optimize transcatheteral application of the embolization media tested (Gelfoam powder, Histoacryl, Ethibloc). Experiments with the model of a normal rat kidney (n = 400) showed that only capillary embolization homogeneously occluding the entire arterial system resulted in complete organ necrosis, while following central (renal artery ligation) or peripheral (Gelfoam powder) occlusion, areas of intact parenchyma remained. Ethibloc/glucose proved to be the embolization medium best suited for capillary embolization (radiopaque, inert, slow resorption). Studies with the model of unilateral renal hypertension of the rat (n = 146) demonstrated the equivalent therapeutic efficiency on blood pressure of Ethibloc embolization (57% cured, 21% improved) compared to surgical nephrectomy (50% cured, 29% improved), whereas renal artery ligation (85% failed) resulted in minor improvement only. In order to adapt capillary embolization with Ethibloc/glucose to clinical angiographic techniques, we performed angioinfarction of canine kidneys (n = 15): the use of a balloon catheter is mandatory. This guarantees blood stasis during the embolization procedure and avoids embolic reflux. Possible clinical indications of capillary embolization in renal hypertension as a less invasive method are, e.g.: malignant nephrosclerosis; renovascular or glomerulonephritic contracted kidneys, and renal dysplasia. Indications for super-selective vaso-occlusion are renal aneurysms, a-v malformations, and segmental hypoplasia.

Angioplasty, Balloon

The proteinase inhibitor complexes (antithrombin III-thrombin, alpha 2antiplasmin-plasmin and alpha 1antitrypsin-elastase) in septicemia, fulminant hepatic failure and cardiac shock: value for diagnosis and therapy control in DIC/F syndrome.

Thrombin (Thr), plasmin (Pl) and elastase (ELP) are serine proteinases which are quickly inactivated by their specific inhibitors (AT III, alpha 2AP, alpha 1AT), if intravascular activation of coagulation and fibrinolytic system or if release from PMN granulocytes by different stimuli (F.I., endotoxin, activated factor XII, a.o.) occurs. The immunological determination of the developing proteinase inhibitor complexes (PIC) AT III-Thr, alpha 2AP-Pl and alpha 1AT-ELP gives information as to whether intravascular coagulation, hyperfibrinolysis or unspecific proteolysis induced by elastase have taken place. Despite the high antiprotease activity in the plasma the a.m. serine proteinases may exert their proteolytic activity towards their specific substrates in vivo. In infectious diseases, fulminant hepatic failure and cardiac shock a complex consumption of coagulation factors and inhibitors may cause severe coagulation defects, microcirculatory disturbances and bleeding tendency. The PICs behaviour was determined in more than 80 patients with infectious diseases, in 5 patients with fulminant hepatic failure (FHF) and 7 patients with cardiac shock. Only in infectious diseases, mainly in septic complications, and septic complications during FHF and cardiac shock, are alpha 1AT-ELP levels found to be highly elevated. After cardiac shock, in FHF and in infectious diseases coagulation and fibrinolysis may additionally be activated. In this case AT III-Thr and alpha 2AP-Pl complexes could be detected in the patients plasma. This indicates that intravascular coagulation and hyperfibrinolysis has additionally taken place. To prevent bleeding complications a replacement therapy with plasma derivatives (AT III, plasminogen concentrate, PPSB and FFP) has been successfully performed in several patients with septic complications and in the 5 patients with FHF and the 7 patients with cardiac shock. No bleeding complication occurred, and the haemostatic balance could be maintained in the treated patients. AT III replacement therapy is necessary to stop DIC, PPSB improves severe coagulation defects, only FFP may additionally provide alpha 1AT, alpha 2AP and factor V. In acute renal failure sometimes plasminogen replacement is necessary to maintain a normal activity of the fibrinolytic system. The complex consumption of coagulation proteins in infectious diseases, FHF and cardiac shock cannot successfully be treated with an anticoagulant such as heparin alone.

Aged

[Extracorporeal lithotripsy in the treatment of renal lithiasis. 5 years' experience].

The historical background to extracorporeal lithotripsy using shock waves is described and indications for use of this treatment discussed in relation to other types of therapy for reno-ureteral lithiasis: percutaneous or trans-ureteral endoscopy. The reduction in invasive surgical procedures is emphasized. The first human use of extracorporeal lithotripsy by shock waves dates back to 1980. Since then, more than 30,000 calculi have been treated in this way, either exclusively or in combination with other therapy. For simple small calculi (less than 1 cm in diameter and situated in the pelvis or a calyx) the incidence of complications is minimal: renal colic (15%), fever (13%), need for complementary therapy (7%). With extension of use of extracorporeal lithotripsy to complex calculi (multiple calculi, staghorn calculi) these figures increased to 30, 5 and 12% respectively. Patients with obstructive and infected lithiasis were treated by percutaneous drainage nephrostomy with intensive antibiotic therapy prior to extracorporeal treatment. Extending indications also provided data on contraindications: coagulation disorders, major vascular problems, abnormal size or weight of patient, pregnancy and finally difficulty in localizing calculi. Of interest is the almost total lack of efficacy of shock waves for treating staghorn calculi. Treatment in these cases should be by an initial percutaneous approach to reduce size of calculus followed by extracorporeal lithotripsy under nephrostomy cover. Surgery for lithiasis should therefore be reserved for complex lithiasis cases with large caliceal calculi proximal to a long narrow infundibulum and to calculi proximal to a stenosis of pyelo-ureteral junction. Whenever possible, lumbar ureter calculi should be raised towards the pelvis by endoscopic manipulation before extracorporeal lithotripsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans