[Enzootic calcinosis in the goat and cow in Switzerland].
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Biomedical subjects
Publications and source records attributed to J Kessler.
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Trigeminal, substance P-containing nerves have been studied in the stretch-prepared rat iris with immunohistochemical techniques. The normal iris exhibited a slightly irregular plexus of individual fibres in the dilator, intermingled with thin, meandering axon bundles. The sphincter contained more circumferentially oriented fibres. Occasional free nerve endings were present in all parts of the iris; no obvious association with blood vessels was detected. All substance P-positive nerves in the iris disappeared after lesioning the trigeminal nerve. Irides of neonates showed scattered, smooth fibres in a sparse plexus, without visible axon bundles. Over the first two postnatal weeks, the density of innervation developed rapidly, reaching a transiently supranormal level and fluorescence intensity, compared to adulthood. From 3 weeks on, the pattern and density of substance P-containing fibres approached the normal adult appearance. In irides grafted to the anterior eye chamber, the intrinsic substance P nerves degenerated, disappearing completely after 5 days. Reinnervation from the host irides transpired over the next few weeks, approximating normal density after 3 weeks, and organotypic density and distribution from 4 weeks on. No obvious hyperinnervation was encountered after longer postoperative times (3 months). In the host iris, many substance P fibres disappear or exhibit low fluorescence intensity during the first postoperative week, recovering fully during the next 2 weeks. Over longer postoperative periods irregular, moderate hyperinnervation developed with increased numbers of axons in bundles. In conclusion, we show normal distribution and plasticity during ontogeny and maturity of substance P-containing iris nerves in the rat, with a sensitive immunohistochemical technique in iris whole mounts.
Spleen cell suspensions of 2 dialysis patients with hepatosplenomegaly and pancytopenia were studied in vitro. Spleen cells of a cadaver kidney donor were studied as control. In spleen macrophages of the patients, silicone particles could be demonstrated with TEM and electron microprobe analysis. Under basal conditions and after stimulation with zymosan and concanavalin A, release of PGE2, TXB2 and 6-keto-PGF1 alpha from patient cells was higher than control cells. This anecdotal observation parallels previous animal studies and suggests that loading of human macrophages with foreign material particles activates arachidonic acid metabolism.
The ability of the rat brain to acquire or to retain specific learning tasks was tested under conditions of multiple lesions and widely different amounts of practice. Lesion targets were (a) the medial prefrontal and cingulate cortex, (b) the anterior and mediodorsal thalamus, and (c) the dorsal and ventral hippocampus. Rats were divided into seven groups. The first group received lesions of all three structural complexes prior to training in a delayed alternation and an active avoidance task. Groups 2-4 received lesions in different combinations of two of the three structural complexes prior to task acquisition. Group 5 first learned both tasks and then received the medial cortical lesion; thereafter it was retrained to criterion. Then, the thalamic lesion was made, and relearning was tested a second time. Finally, the hippocampal region was damaged, and a last relearning test was given. Groups 6 and 7 also first acquired both tasks; however, after that, they received 240 (Group 6) or 1,280 (Group 7) trials of overtraining. Following this, all three structural complexes were given lesions serially before relearning of the two tasks was tested. Nine of the ten animals of Group 1 failed to acquire the alternation task, but all learned the avoidance task. In Groups 2-4, all rats acquired both tasks. Postoperatively, rats of Group 5 were inferior to those of Group 6 in both tasks, and rats of Group 7 were the most successful animals of the last three groups. These results question the assumption that serial lesions with intermittent training between lesions have beneficial effects, and they also stress the importance of task practice, that is, of behavioral experience. It is argued that prolonged training will lead to a widely distributed storage of information within the brain. The process of wide diffusion of information will, however, be disturbed (or at least retarded) by lesions made shortly after task acquisition or task reacquisition (as was the case for animals of Group 5).
Spallation of silicone was evaluated in an in vitro system, using a commercial blood pump and dialysis tubing. Silicone particle release was assessed at various occlusion forces (5.5-22 kp). When the occlusion force was reduced from 22 to 5.5 kp, the number of released silicone particles decreased by approximately 80 per cent; in parallel, the amount of silicone retrieved from the recirculation fluid decreased from 1.6mg to less than 0.23mg. It is concluded that reduction of occlusion pressure within the blood pump effectively reduces spallation of silicone tubing.
Multiorgan, abnormalities in dialysis patients (for example, hepatosplenomegaly, granulomatous hepatitis, cytopenia from hypersplenism) have recently been ascribed to the loading of macrophages (MO) with silicone particles released from the pump segment of dialysis tubing. In the present study, the effect of chronic intravenous or intraperitoneal loading of rats with silicone, polyvinylchloride (PVC) and polyurethane (PU) particles on arachidonic acid metabolism of peritoneal MO and splenic cells was examined in vitro. Intravenous injections of silicone, PVC, or PU particles caused accumulation of the material within the lysosomes of MO of spleen, liver, and lung. Spontaneous release of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was significantly increased in peritoneal MO of rats injected with silicone, PVC, or PU (Control: 4.27 +/- 0.85 ng PGE2/ml/24 hr; silicone 51.9 +/- 13.2; PVC 57.5 +/- 10.6; PU 28.8 +/- 2.3). Zymosan or LPS stimulated PGE2 release from control MO, but caused no consistent further elevation of high basal PGE2 release from MO after particle loading. Furthermore, increased spontaneous and stimulated TXB2 release was also observed in spleen cells of rats given intravenous injection of silicone particles. It is concluded that storage of plastic particles (silicone, PVC, and PU) by macrophages stimulates arachidonic acid metabolism.
The performance in reidentifying photographs was measured in alcoholic Korsakoff patients, in non-amnesic alcoholics and in a control group. The photographs showed well-known and unknown faces and buildings and alcoholic and nonalcoholic beverages. A minimum of 15 min elapsed between the end of the original presentation of the series and the beginning of its second presentation within a large number of additional photographs. Korsakoff patients were significantly inferior in number of correctly reidentified items compared to alcoholics who were in turn significantly inferior to the control group. Korsakoff patients manifested the poorest performance in the reidentification of unknown pictures and of nonalcoholic beverages; they showed, however, comparatively good performance in the reidentification of alcoholic beverages and of known faces. Independent of the category of the stimulus material, the Korsakoff patients had low confidence in their responses. It is concluded from these data that the emotional tone of material to be remembered constitutes a major variable for delayed effective retrieval.
A five-drug parenteral antiemetic regimen was administered to 17 patients experiencing intractable vomiting following treatment with cisplatin-containing combination chemotherapy. The five-drug treatment consisted of metoclopramide (1 mg/kg iv), diphenhydramine (50 mg im), dexamethasone (20 mg iv), diazepam (5 mg iv), and thiethylperazine (10 mg im), given together at the initiation of the regimen and repeated on a predefined schedule. The number of emetic episodes, duration of nausea and vomiting, and adverse effects were recorded by trained observers. In addition, all patients completed standardized evaluation forms on the day after treatment. Thirteen patients (76%) remained free of vomiting and three (18%) had only one emesis after beginning the study treatment. No serious toxicity was encountered. We conclude that intractable vomiting induced by cisplatin-based combination chemotherapy can be successfully terminated with an aggressive parenteral antiemetic regimen.
Behavioral and neuroanatomical effects of hippocampal injections of kainic acid (KA) and tetanus toxin (TT) were investigated in rats. Injections of KA resulted in both local and distant neuroanatomical damage, but not in clear signs of epilepsy; injections of TT on the other hand were followed (in some of the rats) by prolonged seizure attacks, but not by neuronal damage. Based on these results it is suggested that the widespread neuronal damage following KA lesions cannot be primarily attributed to orthodromic activation of epileptic discharges. Instead, specific properties of KA and their interactions with certain transmitters may provoke widespread neuroanatomical damage.
Arthrobacter sialophilus neuraminidase catalyzes the hydration of 5-acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonic acid (2,3-dehydro-AcNeu) with Km and kcat values of 8.9 X 10(-4) M and 6.40 X 10(-4) s-1, respectively. The methyl ester of 2,3-dehydro-AcNeu as well as 2,3-dehydro-4-epi-AcNeu are also hydrated by the enzyme. The product resulting from the enzymatic hydration of 2,3-dehydro-AcNeu is N-acetylneuraminic acid. A series of derivatives of 2,3-dehydro-AcNeu (K1, 1.60 X 10(-6) M) including 2,3-dehydro-4-epi-AcNeu (2.10 X 10(-4) M) and 2,3-dehydro-4-keto-AcNeu (K1 = 6.10 X 10(-5) M) were each competitive inhibitors of the enzyme. The methyl esters of these ketal derivatives were also competitive enzyme inhibitors. Dissociation constants for these ketals were determined independently by fluorescence enzyme titrations which gave values similar to those found kinetically. These six relatives of 2,3-dehydro-AcNeu were also competitive inhibitors for the influenza viral neuraminidases. For the viral neuraminidases, the dissociation constant for 2,3-dehydro-AcNeu and its methyl ester were 2.40 X 10(-6) and 1.17 X 10(-3) M, respectively. The interpretation placed upon the K1 values determined for these ketals against the Arthrobacter versus influenza neuraminidases is that the bacterial enzyme has a more flexible glycone binding site.
The acquisition of a spatial reversal task and two reversals of it and the acquisition of an active two-way avoidance task were tested in three groups of male Sprague-Dawley rats: two experimental and one control group. The experimental group received chemical lesions of the parabrachial nuclei (group NPB) or of the dorsal hippocampus (group HC), using ibotenic acid. (Ibotenic acid is a compound which, contrary to kainic acid, fails to produce distant lesions, but, in conformity with kainic acid, spares the majority if not all fibers of passage.) The control group (group CG) received injections of the vehicle solution only. Animals of group NPB, in comparison to those of the other two groups, acquired the reversal task more quickly, but in the acquisition of its two reversals they needed considerably more time and made more perseverative errors. Likewise, only group NPB was significantly impaired in the acquisition of the avoidance task. From these results and from available evidence on connections of the parabrachial neurons with regions specifically involved in variables of the tested tasks (such as the prefrontal cortex), it is concluded that the parabrachial region exerts an activating influence on forebrain areas.
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Arthrobacter sialophilus neuraminidase catalyzes the hydrolysis of N-acetylneuraminyl-alpha-oxygen, nitrogen, and azido glycosides. The most effective of those substrates examined was N-acetylneuraminyl-alpha-4-methylumbelliferylglycoside (AcNeu-alpha-4-MU; Km app, 0.0193 mM; kcat, 136.4 sec-1). The products resulting from the enzymic hydrolysis of N-acetylneuraminyl-alpha-azido-glycoside were N-acetylneuraminic acid and azide ion. N-acetylneuraminyl-alpha-2,3-thiogalactylglycoside and N-acetylneuraminyl-alpha-2,6-thiogalactylglycoside were competitive inhibitors of the enzyme having KI values of 1.52 mM and 1.70 mM, respectively. Dissociation constants for these thioglycosides were also determined by fluorescence enzyme titrations which gave values similar to those determined kinetically. N-Acetylneuraminic acid, but not its methyl ester, was a competitive inhibitor of neuraminidase. Its KI value, 0.18 mM, was also determined by both methods. 5-Acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-talo-nonulosonic acid (2-deoxy-4-epi-AcNeu) was found to be a weak competitive inhibitor (KI, 12.1 mM). A. sialophilus neuraminidase further catalyzes transglycosidation reactions with methanol as acceptor. Methanol had no effect on the release of 4-MU by enzymatic hydrolysis of AcNeu-alpha-4-MU, suggesting that the formation of the enzyme-glycone intermediate is the rate-determining step. The anomeric configuration of the product of this reaction, as shown by 13C-nmr spectroscopy, is N-acetylneuraminyl-alpha-methylglycoside. Neuraminidase, therefore, catalyzes its reactions with overall retention of configuration.
Behavioral and neuromorphological effects of intraperitoneally injected ibotenic acid (IBO) were investigated in rats. These injections led to a number of marked behavioral disturbances which ultimately resulted in the death of 6 of the 13 IBO-treated rats. Despite marked changes in behavior, no morphological changes could be detected in the brain tissue of the surviving rats.
The performance of rats trained in a radial arm maze was tested before and after chemical lesions of the thalamic mediodorsal nucleus or the ventral tegmental area. Their behavior was compared with that of a sham-operated control group. Lesions were produced with ibotenic acid, a compound that selectively destroys neurons while apparently leaving fibers of passage intact. Results revealed no intergroup difference in the number of errors performed when all six trials were given in one session without interruption. The group with mediodorsal lesions made, however, significantly more errors than either of the other two groups when a delay of 1 hr was interposed between the first four and the last two trials. Furthermore, these rats differed from rats of the other groups in the number of sessions necessary to reach criterion, in the time needed to finish a session, and in the directness with which a goal was approached. Rats with lesions of the ventral tegmental area did not differ from rats of the sham-operated control group in any of the measures taken. It is suggested that the deficits of rats with mediodorsal lesions resemble qualitatively those found in human patients with lesions of the mediodorsal nucleus.
The effectiveness of 13 N-acetylneuraminic acid derivatives as potential inducers of Arthrobacter sialophilus neuraminidase were examined. N-Acetylneuraminic acid nitrogen and thioglycosides were not inducers, whereas 2,3-dehydro-N-acetylneuraminic acid, a transition state analog for neuraminidases, was the most effective inductive ligand. The C-4 hydroxyl function of N-acetylneuraminic acid was essential for enzyme derepression.
Treatment of N-acetylneuraminic acid methyl ester with sulfuric acid and acetic anhydride at 50 degrees followed by deacetylation gave 2,3-dehydro-2-deoxy-N-acetylneuraminic acid methyl ester and methyl 5-acetamido-2,6-anhydro-2,3,5-trideoxy-D-glycero-D-talo-non-2-enonate (2,3-dehydro-4-epi-NeuAc methyl ester) in equal yields (approximately 40% each). The structure of the latter was ascertained primarily from analysis of its mass spectrum and 1H- and 13C-nuclear magnetic resonance spectra. The relative proportions of these two glycals in the foregoing reaction was dependent on temperature, as at 0 degrees, the yield of 2,3-dehydro-4-epi-NeuAc was markedly diminished. A minor by-product of this acetylation reaction was 2-methyl-(methyl 7,8,9-tri-O-acetyl-2,6-anhydro-2,3,5-trideoxy-D-glycero-D-talo-non-2-enonate)-[ 4,5-d]-2-oxazoline. Based upon this finding and additional interconversion experiments, a mechanism involving the intermediacy of the latter oxazoline to account for the epimerization is proposed. These glycals and their methyl esters are competitive inhibitors of Arthrobacter sialophilus, neuraminidase, suggesting that the 4-hydroxyl group must be equatorially oriented for maximal enzyme inhibition.