Analysis of Yersinia pseudotuberculosis Isolates Recovered from Deceased Mammals of a German Zoo Animal Collection.

Yersinia pseudotuberculosis is an important pathogen for both humans and animals. It can infect livestock, as well as pets and wild animals. During recent years, a number of reports have described the isolation of Y. pseudotuberculosis from zoo animals, mainly birds and mammals, for which the infection was mostly lethal. Between 2005 and 2019, there were at least 17 cases of deceased mammals, belonging to five different species, which suffered from a Y. pseudotuberculosis infection at the Zoo Wuppertal, Germany. Since only scarce information exists on the properties of Y. pseudotuberculosis from zoo animals, we characterized eight isolates, covering all infected species, in detail. All isolates were members of biotype 1, but belonged to five serotypes, five sequence types (STs), and seven core-genome multilocus sequence types (cgMLSTs). Using pulsed-field gel electrophoresis (PFGE) analysis and whole-genome sequencing (WGS), the seven isolates could be discriminated from each other. They differed significantly regarding their virulence genes and mobile genetic elements. While the virulence plasmid pYV existed in all serotypes (five isolates), a complete high-pathogenicity island (HPI) was detected only in the serotypes O:1a, O:1b, and O:13 (four isolates), but not in O:2a and O:2b. Similarly, the content of other plasmids and prophages varied greatly between the isolates. The data demonstrate that the deceased mammals were infected by seven individual isolates and not by a single type predominating in the zoo animals.

[Clinical experience with percutaneus large-core needle biopsies of the breast and evaluation of cytopathological and histopathological results]. / Klinische Erfahrungen mit einer kombinierten imprintzytologischen und histopathologischen und Begutachtung von perkutanen Stanzbiopsien der Mamma.

OBJECTIVE: Core needle biopsy (CNB) allows a microinvasive diagnosis of breast lesions. We investigated whether imprint cytology of CNB specimens is a useful method of rapidly obtaining additional diagnostic information. MATERIAL AND METHOD: During five years 46 218 breast examinations for 23 300 patients were performed. 563 patients were examined by CNB. The results of imprint cytology were compared with the histopathological results. Statistical analysis was done for all patients who underwent subsequent surgery. RESULTS: 195 of 563 patients were treated surgically. 155 patients exhibited malign lesions. 40 patients showed benign breast lesions. Four patients with malign findings in imprint cytology and histopathology of CNB were treated conservatively. Imprint cytology had a sensitivity of 0.89, specificity of 0.88, positive predictive value of 0.96 and negative predictive value of 0.67. Histopathology revealed a sensitivity of 0.90, specificity of 0.95, positive predictive value of 0.98 and negative predictive value of 0.70. 364 patients with benign findings in imprint cytology and histopathology were controlled subsequently. One of these patients developed five month later an invasive ductal tumor. CONCLUSION: Imprint cytology of CNB is a reliable method to obtain additional diagnostic information. Inadequate and suspicious cases should be evaluated based on complementary diagnostic procedures for breast lesions.

The main determinant of furosemide inhibition on GABA(A) receptors is located close to the first transmembrane domain.

Inhibitory GABA(A) receptors are regulated by numerous allosteric modulators, the most receptor-subtype specific of which is furosemide. It recognises receptors of the subunit composition alpha6beta2/3gamma2, restricted to cerebellar granule cells. To locate furosemide's site of action we constructed chimeras of the furosemide-sensitive alpha6 and the furosemide-insensitive alpha1 subunit, and expressed and studied them together with the beta3 and gamma2 subunits in Xenopus oocytes by the two-electrode voltage clamp technique. The inhibition of GABA-induced currents by furosemide mainly depended on a short domain proximal to the first transmembrane region of the alpha6 subunit.

A receptor with GABAC-like pharmacology in invertebrate neurones in culture.

We have characterized in crustacean neurones in culture a receptor for gamma-aminobutyric acid (GABA) which conforms to the pharmacological profile of the proposed type-C GABA receptor (GABAC) found in the vertebrate retina. It is associated with a chloride-selective ion channel and is blocked by picrotoxin. It is neither inhibited by bicuculline nor activated by baclofen, while diazepam and phenobarbital are without modulatory effect. Like the GABAC-like receptor of the vertebrate retina it is activated by the folded GABA analogue cis-4-aminocrotonic acid (CACA). Desensitization is moderate allowing for a more sustained action of GABA. Single channel recordings revealed a bicuculline-resistant GABA- and CACA-activated chloride channel with a conductance about eight times higher than that described for the bicuculline-resistant GABA receptor channel from the rat retina.

Effect of minoxidil on the mobility and differentiation of cultivated human keratinocytes.

The mode of topical action of minoxidil (U-10,858, CAS 38304-91-5) ist not entirely clear. The influence of minoxidil on the ultimate differentiation of keratinocytes was investigated. Human keratinocytes (HaCaT-cells) were incubated with minoxidil containing culture medium (10-250 micrograms/ml). Minoxidil inhibited in a concentration dependent manner cell mobility whereas the adhesion area and the cell circumference were increased. The minoxidil treated cultures had a higher desmosome density compared to parallel control cultures and they expressed the suprabasal keratins 1 and 10 (indicating progress in differentiation) earlier and to a larger extent than the controls. Keratins were revealed immunohistochemically and by two-dimensional polyacrylamide gel electrophoresis. The results suggest that minoxidil supports the differentiation of human keratinocytes.

BICUCULLINE/BACLOFEN-INSENSITIVE GABA RESPONSE IN CRUSTACEAN NEURONES IN CULTURE

Neurones were dissociated from thoracic ganglia of embryonic and adult lobsters and kept in primary culture. When gamma-aminobutyric acid (GABA) was applied by pressure ejection, depolarizing or hyperpolarizing responses were produced, depending on the membrane potential. They were accompanied by an increase in membrane conductance. When they were present, action potential firing was inhibited. The pharmacological profile and ionic mechanism of GABA-evoked current were investigated under voltage-clamp with the whole-cell patch-clamp technique. The reversal potential of GABA-evoked current depended on the intracellular and extracellular Cl- concentration but not on extracellular Na+ and K+. Blockade of Ca2+ channels by Mn2+ was also without effect. The GABA-evoked current was mimicked by application of the GABAA agonists muscimol and isoguvacine with an order of potency muscimol>GABA>isoguvacine. cis-4-aminocrotonic acid (CACA), a folded and conformationally restricted GABA analogue, supposed to be diagnostic for the vertebrate GABAC receptor, also induced a bicuculline-resistant chloride current, although with a potency about 10 times lower than that of GABA. The GABA-evoked current was largely blocked by picrotoxin, but was insensitive to the GABAA antagonists bicuculline, bicuculline methiodide and SR 95531 at concentrations of up to 100 µmol l-1. Diazepam and phenobarbital did not exert modulatory effects. The GABAB antagonist phaclophen did not affect the GABA-induced current, while the GABAB agonists baclophen and 3-aminopropylphosphonic acid (3-APA) never evoked any response. Our results suggest that lobster thoracic neurones in culture express a chloride-conducting GABA-receptor channel which conforms to neither the GABAA nor the GABAB types of vertebrates but shows a pharmacology close to that of the novel GABAC receptor described in the vertebrate retina.