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R Kirsch

Publications and source records attributed to R Kirsch.

At least 37 records · Page 2Linked to original sources

Allosteric inhibition of human lymphoblast and purified porphobilinogen deaminase by protoporphyrinogen and coproporphyrinogen. A possible mechanism for the acute attack of variegate porphyria.

Variegate porphyria (VP) is characterized by photocutaneous lesions and acute neuropsychiatric attacks. Decreased protoporphyrinogen oxidase activity results in accumulation of protoporphyrin (ogen) IX and coproporphyrin (ogen) III. During acute attacks delta-aminolevulinic acid and porphobilinogen also increase, suggesting that porphobilinogen deaminase (PBG-D) may be rate limiting. We have examined the effects of porphyrinogens accumulating in VP on PBG-D activity in Epstein-Barr virus-transformed lymphoblast sonicates from 12 VP and 12 control subjects. Protoporphyrinogen oxidase activity was decreased and protoporphyrin increased in VP lymphoblasts. PBG-D in control lymphoblasts obeyed Michaelis-Menten kinetics (Vmax 28.7 +/- 1.8 pmol/mg per h, Hill coefficient 0.83 +/- 0.07). VP sonicates yielded sigmoidal substrate-velocity curves that did not obey Michaelis-Menten kinetics. Vmax was decreased (21.2 +/- 2.0 pmol/mg per h) and the Hill coefficient was 1.78 +/- 0.17. Addition of protoporphyrinogen IX and coproporphyrinogen III to control sonicates yielded sigmoidal PBG-D substrate-velocity curves and decreased PBG-D Vmax. Addition of porphyrins or uroporphyrinogen III did not affect PBG-D activity. Removal of endogenous porphyrin (ogens) from VP sonicates restored normal PBG-D kinetics. Purified human erythrocyte PBG-D obeyed Michaelis-Menten kinetics (Vmax 249 +/- 36 nmol/mg per h, Km 8.9 +/- 1.5 microM, Hill coefficient 0.93 +/- 0.14). Addition of protoporphyrinogen yielded a sigmoidal curve with decreased Vmax. The Hill coefficient approached 4. These findings provide a rational explanation for the increased delta-aminolevulinic acid and porphobilinogen during acute attacks of VP.

Cell Line, Transformed↗

The effects of inhibition of plasma cholinesterase activity on systemic toxicity and blood catecholamine levels from cocaine infusion in pigs.

We investigated systemic effects and possible mechanisms for lethality of intravenously infused cocaine in spontaneously breathing and mechanically ventilated unconscious Landrace male pigs weighing about 26 kg (25.75 +/- 0.25 kg) that were pretreated with either saline solution (groups 1 and 3) or iso-ompa (tetraisopropyl pyrophosphoramide), a specific plasma cholinesterase inhibitor (groups 2 and 4). Pigs were made unconscious with sodium thiopental and ventilated with 70% nitrous oxide and 30% oxygen. A carotid arterial cannula and a Swan-Ganz catheter were inserted for hemodynamic monitoring. Pigs in groups 1 and 2 were then allowed to breathe spontaneously and groups 3 and 4 were mechanically ventilated. After obtaining a stable state, as judged by cardiovascular and respiratory parameters, the pigs were infused intravenously with cocaine hydrochloride (0.8 mg/kg/min) until the time of cardiac arrest. Respiratory and cardiovascular parameters, blood temperature, and sodium and potassium levels were monitored. The times of occurrence of respiratory arrests (RA), cardiac arrests (CA), and convulsions were recorded. Our results showed that RA is the primary cause of death in spontaneously breathing pigs and that mechanical ventilation significantly delayed the occurrence of CA (p < 0.05). Significant decreases in cardiac output, mean blood pressure, and heart rate as well as significant increases in systemic and pulmonary vascular resistances, central venous and pulmonary wedge pressures, and blood K+ levels were noted in mechanically ventilated pigs (p < 0.05). Variable hemodynamic responses were noticed in spontaneously breathing pigs. Our results also showed that no significant changes occurred in blood catecholamine levels when compared with baseline values associated with the infusion of toxic doses of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Secondary metabolites by chemical screening. 9. Decarestrictines, a new family of inhibitors of cholesterol biosynthesis from Penicillium. II. Structure elucidation of the decarestrictines A to D.

The structures of the novel 10-membered lactones, named decarestrictines A1/A2 (1/2), B (3), C1/C2 (5/6) and D (7), are presented. The structures of these secondary metabolites, isolated from different Penicillium species, were established by spectroscopic analysis and confirmed by X-ray analysis of 7 and a derivative of 3 leading to the stereochemical information. The decarestrictines vary in the oxygenation pattern between C-3 and C-7 and show structural similarities to known lactones from other fungi.

Anticholesteremic Agents↗

Effects of temperature, steroids and castration on daily torpor in the Djungarian hamster (Phodopus sungorus).

1. In Phodopus sungorus the frequency and characteristics of daily torpor were not affected by a decrease in temperature. The seasonal cycle of daily torpor is essentially under photoperiodic control. 2. Testicular regression is a necessary condition for daily torpor occurrence. Testosterone and 5 alpha-dihydrotestosterone administration totally inhibited daily torpor in hamsters which were exposed to short days. The temporal inhibition of torpor by steroids had no effect on the seasonal time measuring mechanism governing daily torpor. 3. Castration influenced certain aspects of the daily torpor display. Castrated hamsters showed a delay in terminating torpor season lending further support to the hypothesis that recrudescence of the testis plays a role in terminating the daily torpor season. Castration, when performed before or on the day of transfer to short photoperiod led to an increase in the frequency of torpor bouts and reduce SP exposure duration which is necessary for the daily torpor season beginning.

Animals↗

Daily torpor in the Djungarian hamster (Phodopus sungorus): photoperiodic regulation, characteristics and circadian organization.

1. The daily torpor was measured by oxygen uptake in Djungarian hamsters during adaptation to a short photoperiod (SP: 10L, 14D) at 20 degrees C. In these constant conditions the torpor presented metabolic characteristics and a daily time course independent of the duration of adaptations to SP. 2. The frequency of torpor bouts increased during SP exposure and its maximum was reached after about 130 days. The frequency of torpor was greater in males than in females. 3. The incidence of torpor was increased by constant dark exposure and this is discussed as a protective mechanism for the individual animal's ability to survive. 4. The temporal organization of daily torpor was demonstrated to be directly synchronized by the day-night cycle and to be controlled by an endogenous circadian function.

Animals↗

Role of intestinal mucus in crystal biogenesis: an electron-microscopical, diffraction and X-ray microanalytical study.

In the posterior intestine of the sea-water eel, mucus plays an important role in biocrystallization of calcium ions. By means of transmission and scanning electron microscopy associated with X-ray microanalysis and X-ray diffraction it has been possible to determine the role of mucous fibers as nucleation sites. Biocrystallization occurs in 2 steps: (1) Calcification of mucus. As soon as mucus is excreted in the intestinal lumen, it is loaded with calcium, as shown by lanthanum affinity and X-ray microanalysis on freeze-dried tissues. (2) Genesis of crystals. Needle-shaped crystallites build up in coalescent spherites in the intestinal lumen near the microvilli. Genesis occurs as follows: (a) crystallite mineralization by nucleation in an organic matrix composed of glycoproteinaceous mucous fibers, followed by the appearance of spherites; (b) coalescence in spherites and association of spherites in rhombohedra; (c) extrusion of organic material during the final step of crystallization.

Animals↗

Central vasopressin infusion prevents hibernation in the European hamster (Cricetus cricetus).

The amount of immunocytochemically detectable vasopressin in the brain of the European hamster (Cricetus cricetus) shows a seasonal variation; i.e., dense vasopressin immunoreactivity is present in the lateral septum during summer but is absent in autumn and winter [Buijs, R. M., Pévet, P., Masson-Pévet, M., Pool, C. W., De Vries, G. J., Canguilhem, B. & Vivien-Roels, B. (1986) Brain Res. 371, 193-196]. In the winter period the European hamster hibernates. Since vasopressin in the lateral septum is known to be involved in the control of body temperature, we investigated whether infusion of vasopressin in the lateral septum during autumn-winter could influence hypothermic patterns normally seen in hibernating animals. Hamsters whose lateral septum was infused with vasopressin showed almost no periods of hypothermia, whereas hamsters treated with control infusions displayed a normal hibernation pattern. The results indicate that persistence of vasopressin release in the lateral septum of the European hamster during winter can prevent hibernation.

Animals↗

Study of e+

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Journal Article↗

Is mucus involved in biocrystallization? Study of the intestinal mucus of the sea-water eel Anguilla anguilla L.

Freeze-dried intestinal mucus of sea-water-adapted eels was analysed by scanning electron microscopy (SEM) and X-ray microanalysis. Calcite crystals were observed in the mucus fibres; their concentration increased along the hindgut. Random SEM observations made in situ indicated that mucus fibres were involved in the genesis of these crystals. Calcium-rich mucus globules were found fused inside crystal matrices. Single typical rhombohedric crystals of various complexity appeared within the mucus framework. The steps of crystal biogenesis were reconstituted in in-vitro conditions.

Anguilla↗

[Pathology and control of virus-induced enteritis in calves].

Considerable economic loss can arise from virus-caused enteritis in calves, in the form of so-called infectious factor diseases, which often develop more seriously when bacterial organisms, such as E. coli become involved. Rota-, corona- and parvoviruses are of particular interest. These pathogens have a marked predilection for intestinal epithelium. Rotavirus destroys the epithelial cells of the upper parts of the villi. Coronavirus penetrates to the base of the small intestinal villi and the superficial and crypt colonic epithelium is frequently affected. Infection of the small intestinal crypt epithelium is characteristic of parvovirus; loss of epithelium at the villus tip is also observed. Damage of the mucosa results in a reduction in digestive and absorbing capacity. It is not possible to treat these virus strains specifically. Great importance is therefore attached to the vaccination of dams as immune prophylaxis. Consumption of sufficient colostrum and milk from vaccinated dams affords the calves good protection. The mechanism is based on the presence of milk antibodies in the calf's intestine which neutralise orally ingested pathogens.

Animals↗