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Biomedical subjects

B Walther

Publications and source records attributed to B Walther.

At least 55 records · Page 3Linked to original sources

Characteristics of a proteinase from ovarian fluid of the lumpsucker (Cyclopterus lumpus L.).

1. A proteinase has been isolated from the ovarian fluid of the lumpsucker (Cyclopterus lumpus). 2. The enzyme was purified essentially to homogeneity by a one step purification procedure using anion-exchange chromatography. 3. The mol. wt of the denatured enzyme is approximately 20,000 as judged by SDS-polyacrylamide gel electrophoresis. 4. The enzyme is inhibited by serine-proteinase inhibitors and acts in the manner of a trypsin-type proteinase both with respect to specific peptide substrates and enzyme inhibitors. 5. The lumpsucker proteinase exhibits low general proteolytic activity but acts effectively on the specific chromogenic peptide substrates.

Animals↗

The effects of pneumatic antishock garments in the treatment of critical abdominal injuries in rats.

Thirty rats were subjected to a standardized critical aortic injury and divided into six groups. In addition to controls, the animals were treated with a pneumatic antishock garment (PASG), massive intravenous or intra-aortic saline infusion, or PASG in combination with either massive intravenous or intra-aortic saline infusion. Twenty-six rats were subjected to a standardized hepatic injury and divided into four groups. In addition to controls, the animals were treated with PASG, massive intravenous saline infusion, or PASG in combination with massive intravenous saline infusion. These animals were allowed to bleed for 5 minutes before the treatment was started. The treatment with PASG alone prolonged the median survival time significantly from 7 min in the control group to greater than 120 min in the PASG group in rats with an aortic injury and from 33 to greater than 120 min in rats with a hepatic injury. Intravenous infusion of saline did not prolong the median survival time. Intravenous infusion in combination with PASG did not have any positive effects on median survival time or median mean aortic pressure and failed to prolong the median survival time significantly in rats with a liver injury, as six out of eight animals developed a lethal pulmonary edema.

Abdominal Injuries↗

Brain mitochondrial cytochrome P-450scc: spectral and catalytic properties.

The cytochrome P-450-dependent cholesterol side chain cleavage system of the brain has been studied using nonsynaptic mitochondria as the source of enzymatic activity. The system has been found to bind cholesterol and 11-deoxycorticosterone, producing type I difference spectra, whereas the binding of pregnenolone induced a reverse type I difference spectrum. Inhibitors of cytochrome P-450-linked monooxygenase activities produced type II spectra. The formation of labeled pregnenolone after incubation of brain mitochondria with [4-14C]cholesterol has been obtained, and this formation was inhibited by glutethimide, a specific inhibitor of cytochrome P-450scc. The functional significance of this enzymatic activity is discussed.

Aminoglutethimide↗

Ethoxyresorufin O-deethylase activity in rat brain subcellular fractions.

Non-polar, lipid-soluble drugs or xenobiotics are able to cross the blood-brain barrier. The brain cytochrome P-450-dependent monooxygenases may oxidize these molecules to more polar and somewhat hazardous metabolites responsible for neurotoxicity. In order to characterize the cytochrome P-450 dependent aryl hydrocarbon hydroxylase activity in brain subcellular fractions, we used 7-ethoxyresorufin as a substrate, as its O-deethylation reflects specifically the activity of the cytochrome P-450 isoform which metabolizes and is induced by polycyclic aromatic hydrocarbons. The results reported here show that this enzymatic activity occurs in both microsomal and mitochondrial fractions, and that the induction after 3-methylcholanthrene treatment remains limited, thus preventing the formation of high levels of harmful metabolites.

Animals↗

Effects of fundoplication on the antireflux mechanism.

Forty patients with a diagnosis of gastro-oesophageal reflux disease established by 24-h ambulatory pH monitoring were treated by a short 360 degrees fundoplication. Results of postoperative evaluation at 6 months were compared with those from 50 normal volunteers. The amount of gastro-oesophageal reflux at pH monitoring decreased significantly and was less than the reflux in the normal subjects. The pressure and the intra-abdominal length of the distal oesophageal high-pressure zone increased significantly. The pressure was similar to that in the normal subjects while a significantly longer intra-abdominal part of the high-pressure zone was created. The clinical results of the operation were evaluated in 38 patients by an independent gastro-enterologist, and were considered to be excellent in 22 patients, good in 13, fair in 2 and poor in 1 patient. The antireflux procedure provided good control of the gastro-oesophageal reflux in our patients by restoring the major components of the antireflux mechanism.

Adult↗

Composition of the refluxed material determines the degree of reflux esophagitis in the dog.

To evaluate the influence of the composition of refluxed material in the pathogenesis of esophagitis, a dog model was used to allow esophageal reflux of gastric secretions, duodenal pancreaticobiliary secretions, and a combination of both. Control dogs had only an esophageal incision. Incompetence of the cardia was established in five other groups by transecting the distal sphincter and creating a hiatal hernia. Two groups received moderate or maximal histamine stimulation of gastric secretion. A gastrojejunostomy, pyloromyotomy, and duodenal closure distal to the papilla were added in the other three groups, creating duodenogastric reflux; two were stimulated with histamine and one had a truncal vagotomy and no histamine. Radiologic, manometric, and pH studies showed that incompetence of the cardia was obtained. The dogs were killed 4 wk postoperatively and evaluated for gross and microscopic evidence of esophagitis. Erosive esophagitis was found only in dogs with reflux of gastric juice following maximal acid stimulation. Microscopic reflux changes in esophageal mucosa were seen in all groups; again, changes were most pronounced in dogs with maximal gastric stimulation. The combination of duodenogastric reflux and moderate gastric stimulation produced more significant alterations in microscopic reflux criteria than did moderate gastric stimulation alone. Our conclusions are as follows: In a dog model of gastroesophageal reflux of various combinations of gastric and duodenal secretory components, erosive esophagitis occurred only with maximal gastric stimulation in the absence of duodenogastric reflux. All reflux combinations, however, produced some degree of microscopic changes, suggesting they could eventually cause gross changes with a lengthened experimental time span.

Animals↗

The activity of 1-naphthol-UDP-glucuronosyltransferase in the brain.

Cerebral microsomes catalysed efficiently the glucuronidation of 1-naphthol, this formation of glucuronide being activated by treatment with Triton X-100 or digitonin. Activated microsomes from the brain of the rat conjugated 1-naphthol with an apparent Km of 95 microM and a Vmax of 5.47 nmol/hr mg protein at 30 degrees C. Microsomal uridine diphosphate (UDP)-glucuronosyltransferase activity in brain towards 1-naphthol was not significantly induced by pretreatment of animals with 3-methylcholanthrene or phenobarbital. These data suggest that UDP-glucuronosyltransferases in brain are different from the hepatic enzymes with regard to biochemical parameters and in response to inducers of drug metabolism. The hepatic UDP-glucuronosyltransferase deficiency in Gunn rats was also observed in the brain.

Animals↗

Quantitative measurement of cerebral cytochrome P-450 by second derivative spectrophotometry.

Second order derivative spectrophotometry was used to improve the accuracy and reproducibility of cytochrome P-450 measurements in subcellular fractions obtained from the brain. This method allowed better resolution of the overlapping bands of cytochrome P-450 and other iron proteins, as well as a reduction of the effects of turbidity and non-specific components. Using this method, the cytochrome P-450 content of rat brain mitochondrial and microsomal fractions was measured to be 74.2 +/- 2.3 and 5.9 +/- 0.3 pmol/mg protein, respectively.

Animals↗

Identification of infants at risk for infantile spasms by neonatal polygraphy.

Reevaluation of neonatal EEGs and polygraphic tracings of 40 infants with infantile spasms and/or hypsarrhythmia resulted in the constitution of a compound score for the identification of infants at risk for infantile spasms by neonatal EEG. The score comprises 8 distinct items: 2 concern behavioral characteristics, 6 abnormality of EEG background activity and paroxysmal events. A tracing registered at conceptional age 36 to 44 weeks (eventually up to 50 weeks) presenting at least 4 of these 8 items is scored positive for the risk of evolving hypsarrhythmia. In a prospective study the polygraphic tracings of 941 newborn infants were evaluated for risk: 18 infants suffering from perinatal distress and 7 newborns with malformations of the brain were scored positive and all 25 developed infantile spasms and/or hypsarrhythmia. One infant with later infantile spasms was missed by the scoring system. None of the remaining infants scored negative manifested infantile spasms. Thus, correct positive prognostication was 100% and false negative 0.1%. By conventional EEG 5 out of 8 patients with infantile spasms were correctly predicted. The high validity of the risk-score based on polygraphic tracing between conceptional age 36 to 44 weeks may allow pre-onset treatment preventing secondary mental deterioration due to hypsarrhythmia and infantile spasms.

Electroencephalography↗

Subcellular distribution of cytochrome P-450 in the brain.

The subcellular distribution of the monooxygenase complexes in the brain was studied by using subcellular fractionation and characterization of these fractions by marker enzymes. Cytochrome P-450 was found to be mainly localized in both synaptic and non-synaptic mitochondria; only a small quantity of enzyme was also found in the microsomal fraction. Peeling off the outer membrane of mitochondria showed that the protein was retained in the inner membrane fraction. A comparative study among some other species confirmed the mitochondrial prevalence of cerebral cytochrome P-450. A partial purification of the rat brain mitochondrial P-450 was obtained.

Animals↗

Effect of central noradrenaline depletion on corticosterone levels and gastric ulcerations in rats.

Effects of central noradrenergic depletion on the stress responses of rats were explored using the new selective neurotoxin (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)). Noradrenergic depletion using DSP-4 was followed by a reduction in basal corticosterone levels after 7 days. Three weeks after DSP-4 treatment, animals exhibited less severe and fewer gastric ulcerations than control animals following 23 h immobilization stress, but stress levels of corticosterone were similar for the two groups. No differences could be found in the peripheral gastric levels of noradrenaline between experimental and control animals, while central noradrenaline was reduced to approximately 30% of control levels. The data support previous findings using other methods that central noradrenaline is an important factor in stress-induced gastric ulceration. The peripheral mechanisms for the protective effects of DSP-4 remain to be elucidated, and studies of these may cast light on the efferent pathways between the central nervous system and gastric mucosa which are involved in stress-induced gastric pathology.

Animals↗

A monoclonal antibody that detects myoepithelial cells in exocrine glands, basal cells in other epithelia and basal and suprabasal cells in certain hyperplastic tissues.

Myoepithelial and luminal cells of human exocrine glands can be positively identified with two different monoclonal antibodies. Myoepithelial cells including those of the salivary gland, mammary gland and sweat gland are positively identified by an antibody CKB1. This antibody does not stain luminal cells, but stains the basal cell layer of certain human stratified epithelia and a few basal cells in simple epithelia. Thus myoepithelial cells and basal cells have certain common features. Luminal cells can be positively stained with the CK5 monoclonal keratin antibody specific for keratin polypeptide 18; this antibody does not stain myoepithelial cells. Of interest is that CKB1 also appears to stain basal and suprabasal cells in certain hyperplastic conditions.

Antibodies, Monoclonal↗

Length of the distal esophageal sphincter and competency of the cardia.

Pressure and abdominal length of the distal esophageal sphincter are important factors in maintaining competency of the cardia against challenges of intraabdominal pressure. Some patients with normal distal esophageal sphincter pressure and position may have reflux which could be due to the inability of the cardia to overcome challenges of intragastric pressure. Three experimental studies and one clinical study were designed to evaluate this problem. The results showed that the resistance to flow through the cardia is related to the integrated effect of distal esophageal sphincter pressure and length; the ratio of distal esophageal sphincter to intragastric pressure necessary to maintain competency is inversely related to the length of sphincter present; gastric dilatation has an adverse effect on the degree of competency achieved by a given distal esophageal sphincter length; and patients with an overall distal esophageal sphincter length of 2 cm or less measured at rest in the fasting state are subject to reflux caused by gastric dilatation, increased intragastric pressure independent of intraabdominal pressure, or both.

Adolescent↗

Cimetidine inhibits cerebral and hepatic mitochondrial respiration in rat.

The presence of cimetidine in the incubation medium of rat brain mitochondria caused decreased oxygen uptake, especially during oxidative phosphorylation (state 3). This inhibition of the respiratory control and of ATP synthesis was dose-dependent. The same observations were made for hepatic mitochondria. The significance of these results is discussed in terms of both the neurological side-effects of cimetidine and its effect on regulatory mechanisms of cerebral or hepatic blood flow.

Animals↗

Healing of esophagojejunal anastomoses after experimental total gastrectomy. A comparative study using manually sutured or stapled anastomoses.

In construction of the eosphagojejunostomy after total gastrectomy, the EEA stapled (US Surgical Corporation, Norwalk, CT) and the two-layer interrupted 3-0 Dexon anastomoses are compared concerning the radiological appearance, breaking strength, circulation, and collagen concentration. Thirty female pigs were used. After total gastrectomy and Roux-en-Y preparation, the pigs were randomized to achieve sutured or stapled anastomoses. 141Ce-labeled microspheres were used for measurements of anastomotic blood flow. After the pigs were killed, the breaking strength of the anastomosis was recorded, the collagen content determined, and an anastomotic index calculated comparing two perpendicular diameters in the anastomosis and 5 cm above. Breaking strength, leakage frequency, and anastomotic index were the same in the two groups. One week after surgery, there was a significant increase in anastomotic circulation (p less than 0.05) in both the sutured and the stapled anastomoses compared to controls. Collagen increased equally with time in the two groups (p less than 0.01). The stapled esophagojejunostomy was faster to perform (20 min) than the sutured (28 min) (p less than 0.05).

Animals↗

Behavioral effects after ibotenic acid, 6-OHDA and electrolytic lesions in the central amygdala nucleus of the rat.

Selective lesions of central amygdaloid neurons with ibotenic acid and electrolytic destruction of the nucleus both led to marked increases in open field activity and activity during passive avoidance conditioning. However, electrolytic lesions of both neurons and fibers resulted in the most pronounced passive avoidance impairments and it is suggested that this lesion effect should be attributed to a combined destruction of intrinsic neurons and neurons located outside the central amygdala nucleus. The 6-OHDA lesions resulted in no significant changes in the behavioral parameters under investigation or in plasma corticosterone levels. The lack of reduced corticosterone levels in any of the lesioned groups do not indicate that general fear arousal is critically dependent on intact central amygdala neurons in the rat. The behavioral data are, however, still compatible with a hypothesis of a temporary reduction in fear arousal during the initial phase of the passive avoidance conditioning.

Amygdala↗