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Biomedical subjects

J Wiesner

Publications and source records attributed to J Wiesner.

54 records · Page 3Linked to original sources

[Regional therapy breast cancer liver metastases].

The prognosis of patients with metastatic breast cancer in particular with an involvement of the liver has to be regarded as rather unfavourable. Up today no convincing therapy for patients with breast cancer and liver metastases could be found. From 1982 to 1991 42 patients with suspicion on liver metastases of a primary breast cancer were laparotomized. At that time 20 patients already had an extrahepatic formation of metastases. In contrast to the preexaminations an histologically benign liver tumor was intraoperatively verified in 6 patients. In the other 36 patients the operation was finished in 9 cases as explorative laparotomy (group A) because of extensive intra- and extrahepatic manifestation and/or vessel abnormalities. In 19 cases an arterial catheter system with subcutaneous port was implanted (group B). Partial liver resection combined with intraarterial catheter implantation was performed in 8 patients (group C). Postoperatively 27 patients monthly received a regional combined chemotherapy (groups B+C); a modified FAM scheme (5-Fluorouracil: 1000 mg/12 h/d/2 d, Adriamycin: 20 mg/12 h/d/3 d, Mitomycin C: 10 mg/2 h/d/1 d) was used. Response could be documented in 12 out of 17 evaluable patients (70.6%). A median overall postoperative survival time of 14.5 months for all patients in case of a proved liver metastases was calculated. A prolongation could not be realized, neither in patients with partial liver resection with regional therapy (group C) nor in patients with an intraarterial chemotherapy (group B). Only in exceptional cases a successful regional chemotherapy could influence the course favourable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Susceptibility of chicken embryos to group A streptococci: correlation with fibrinogen binding.

One problem in investigating group A streptococcal infections and virulence is the lack of appropriate in vivo models. In this study we introduce the chicken embryo model for determining virulence of Streptococcus pyogenes. We found that M protein positive strains, if administered intravenously, were highly virulent for 12-day-old chicken embryos. The LD50 of the strains tested could be correlated directly with the amount of cell wall exposed M protein, which has been determined by the capacity of streptococci to bind fibrinogen and by the ability of streptococci to survive in fresh normal human blood. The number of colony forming units (cfu) of M+ strains necessary to kill 50% of embryonated eggs was significantly lower (< 10(2) cfu) than for M-variants (> 10(4) cfu). Albumin and/or IgG binding streptococcal cells, which can also take place in proteins of the M protein family which do not bind to fibrinogen, did not show that clear correlation to the virulence in chicken embryos that did fibrinogen binding. Application of anti-streptococcal M protein antisera from chicken and rabbit reduced the lethality of the chicken embryos. In contrast, no correlation was found between lethality of chicken embryos and the in vitro production of erythrogenic toxins by the administered strains. Thus the results indicate that the presence of M-protein with its fibrinogen binding activity on the streptococcal cell surface is necessary for virulence of group A streptococci in the chicken embryo model.

Animals↗

[Antibacterial efficiency and toxicity of hydrogen peroxide and other antiseptics].

The results suggest a relatively favourable relation between minimum bactericidal concentration (enterococci) and toxic agent concentration (chicken embryos) of hydrogen peroxide in comparison with chlorhexidin-digluconate, sodium-tosylchloramide and peracetic acid. For chlorhexidin-digluconate a somewhat more favourable relation between minimum bacteriostatic and toxic concentration of the agent was established.

Animals↗

Long-term potentiation of evoked and spontaneous neuronal activity in the grafted hippocampus.

Adult rats with unilateral fimbria-fornix lesion received fetal hippocampal grafts into the lesion cavity. Seven to ten months after the transplantation the graft was examined for long-term potentiation (LTP) in response to host hippocampus and direct graft stimulation. High frequency tetanizing trains delivered to either the host hippocampus or the graft resulted in augmented field potentials and prolonged neuronal discharges in the graft lasting several hours. Very low currents (10-30 microA) were required to induce LTP by direct graft stimulation. In addition to the enhancement of evoked responses, the frequency of occurrence of spontaneously occurring EEG spikes and concurrent population neuronal bursts in the graft increased significantly after the tetanizing trains. These findings suggest that the physiological-biochemical mechanisms required for plastic changes of synaptic efficacy are present in the grafted hippocampus.

Action Potentials↗

Influence of splenectomy on first set rejection reactions of C57BL/6 females to male skin isografts.

The tempo with which C57BL/6 females reject male skin isografts is determined in part by the immunogenicity of the H-Y antigen and in part by the capacity of the host to respond immunologically. Our studies indicate that the spleen plays an important role in determining the briskness of the rejection process in that splenectomy 7-30 days before grafting with male skin significantly shortens the survival time. The results of reconstitution experiments suggests that a population of cells is present in spleens of normal, but not specifically sensitized, females which can restore the conventional first set reaction in splenectomized females. It is inferred that this resident population normally operates in spleen-intact females to delay the development of specific effector responses. Lymphoid cells from H-Y antigen-sensitized, splenectomized females failed to evoke graft-vs.-host responses in males whereas similar cells from females with spleens intact did possess graft-vs.-host potential.

Animals↗

Acute antagonism of dopamine D2-like receptors by amisulpride: effects on hormone secretion in healthy volunteers.

Amisulpride is a selective D2-like dopamine receptor antagonist with a high affinity for the cloned D2 and D3 receptors. At low doses it may improve depressive and negative schizophrenic symptoms whereas antipsychotic effects on positive schizophrenic symptomatology require higher dosages. Acute endocrine effects were studied for two doses of amisulpride with regard to the daytime secretion of prolactin, thyroidea stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH) and cortisol. Amisulpride was administered i.v. to eight healthy male volunteers in a single-blind trial under a randomized cross-over, placebo-controlled design using doses of 20 mg or 100 mg, or saline. The drug was injected at 09:00 h, and plasma samples were withdrawn from 08:30 h to 16:00 h at intervals of 15 and 30 min, respectively. At both dosages, prolactin was significantly elevated to the eight- to ten-fold of baseline levels. Likewise, a significant 50% elevation of TSH concentrations with a trend to a greater increase under the 100 mg dose was observed. Plasma levels of LH and cortisol were not significantly affected by amisulpride. With regard to GH secretion, there was a trend to a decrease only with the 20 mg dose. These results indicate that the neuroendocrinological side-effect profile of acute amisulpride administration may be similar to conventional neuroleptics, and that there are only minor dose-dependent differential effects on hormone secretion in the dose range investigated.

Adult↗

Adenosinergic modulation of homocysteine-induced seizures in mice.

Homocysteine thiolactone (HTL) elicits seizures in mice at a dose of 850 mg/kg (95-100% of animals) with an average latency time of 19.5 min. These seizures are reversed by both 5' N-ethylcarboximide adenosine (NECA) and flunitrazepam, with respective ED50 doses of 0.025 and 0.20 mg/kg. NECA was approximately four-fold more potent as an inhibitor of HTL-induced seizures than of seizures induced by pentylenetetrazol (PTZ, 75 mg/kg). Flunitrazepam was equipotent in both seizure paradigms. The purine precursor 5-amino-4-imidazole carboxamide riboside, (AICAr), although virtually ineffective against PTZ-induced seizures at doses greater than 1 g/kg, was able to inhibit HTL-induced seizures with an ED50 of approximately 350 mg/kg. The anticonvulsant effect of AICAr was dose and time dependent. The anticonvulsant potency of AICAr was increased by simultaneous administration of the adenosine uptake blocker Mioflazine, whereas the central nervous system (CNS)-impermeable adenosine uptake blocker dipyridamole had no effect. The ability of AICAr to permeate the blood-brain barrier (BBB) is limited (less than 1%) and may explain its low potency as an anticonvulsant. AICAr also has very low potency at brain adenosine A1 and A2 receptors as well as adenosine uptake sites (IC50 greater than 10(-3) M), suggesting that its anticonvulsant properties are not mediated by direct action at these sites. The results indicate that AICAr does have frank anticonvulsant effects and further suggest that HTL-induced seizures may represent a useful paradigm for evaluation of adenosinergic agents. AICAr or more potent derivatives thereof may represent a new class of anticonvulsants with the ability to target seizure foci selectively.

Adenosine↗

[Prevalence of nonmevalonate and mevalonate pathways for isoprenoid biosynthesis among bacteria of different systematic groups].

The effect of fosmidomycin and mevinoline, inhibitors of the nonmevalonate and the mevalonate pathway of isoprenoid biosynthesis, respectively, on the growth of 34 anaerobic and 10 aerobic prokaryotic strains was studied. Fosmidomycin at the concentrations used was shown to inhibit the growth of 9 (of 10) representatives of the family Microbacteriaceae, 4 (of 5) strains of Thermoanaerobacter, and 11 (of 12) strains of Clostridium, whereas mevinoline inhibited the growth of lactobacilli (Carnobacterium), methanogenic and sulfate-reducing bacteria insensitive to fosmidomycin. During the late growth phase, four strains of actinobacteria (of nine) accumulate the compound, which, upon oxidation, generates a long-lived free radical; three strains synthesize 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEC). It was concluded that the difference in the sensitivity of the organisms to fosmidomycin and mevinoline might serve as a test to differentiate several representatives of the family Microbacteriaceae. The use of mevinoline for inhibiting methanogens in ecological investigations seems to be promising.

Bacteria↗

[Isoprenoid pigments in representatives of the family Microbacteriaceae].

By using fosmidomycin and mevinolin (inhibitors of the synthesis of isoprenoid pigments), spectrophotometry, and mass spectrometry, the presence of isoprenoid pigments is shown in 71 of the 78 strains under study. All of these strains belong to 11 genera of the family Microbacteriaceae. Yellow, orange, and red pigments are found to have absorption spectra typical of C40-carotenoids. Eight out of the sixteen strains of the genus Microbacterium are able to synthesize neurosporene, a precursor of lycopene and beta-carotene. The biosynthesis of carotenoids in some representatives of the genera Agromyces, Leifsonia, and Microbacterium is induced by light. Inhibition of the biosynthesis of isoprenoid pigments by fosmidomycin suggests that they are synthesized via the nonmevalonate pathway. Twelve strains are found to exhibit both the nonmevalonate and mevalonate pathways of isoprenoid synthesis. These data, together with the difference in the inhibitory concentration of fosmidomycin, can be used for differentiating various taxa within the family Microbacteriaceae.

Actinomycetales↗