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Biomedical subjects

S Zorn

Publications and source records attributed to S Zorn.

13 recordsLinked to original sources

Ultrasonographic detection of abdominal abscess in two guinea pigs.

Two guinea pigs (Cavia porcellus) with clinical signs of anorexia, weight loss, depression and abdominal enlargement were examined. During ultrasound examination, a fluid-filled anechogenic structure 3-4 cm in diameter, with echogenic spots and a highly echogenic thick wall, was found in the pelvic region in one case and connected to the liver in the other case. An abscess or a cyst was suspected and surgical treatment including laparotomy was performed. By histopathological examination performed after surgery, a liver abscess was diagnosed in one guinea pig and an abscess in the pelvic region in the other animal.

Abdominal Abscess↗

Abdominal ultrasonography in pet guinea pigs.

Ultrasonographic examination of 40 pet guinea pigs was performed in the framework of this study. Preparation of the patient for ultrasonography and the examination procedure are described. Normal ultrasonographic findings of the abdominal organs including the liver, spleen, kidney and urinary bladder are presented and illustrated for the first time in this species. Ultrasonography was found to be a useful investigative tool in the diagnosis of abdominal diseases in guinea pigs. In comparison to other diagnostic methods like physical examination including palpation, haematological examination, radiography and diagnostic laparotomy, ultrasonography offers a rapid, non-invasive and reliable means of diagnosing abdominal diseases in this species.

Abdomen↗

Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia.

Available evidence indicates that clozapine is the most effective antipsychotic currently used for the pharmacotherapy of schizophrenia. Unfortunately, clozapine can cause serious side effects that limit the use of the drug. The therapeutic mechanism of action of clozapine is poorly understood, and accordingly, it has been difficult to design new drugs with the advantageous therapeutic properties of clozapine. Based on hypotheses that dopaminergic and serotonergic receptor-blocking properties of clozapine account for its clinical efficacy, several novel antipsychotic drugs have been introduced recently. There is currently insufficient data to reach definitive conclusions regarding the efficacy of the newer 'atypical' antipsychotics in comparison to clozapine. However, most published studies, and general clinical impressions, suggest that none of the newer drugs are as effective as clozapine in treating patients resistant to typical antipsychotic drug therapy. The present paper briefly reviews the clinical experience with the newer 'atypical' antipsychotic drugs and then discusses clinical and preclinical data potentially relevant to mechanisms of action of clozapine in relation to the NMDA receptor hypofunction hypothesis of schizophrenia.

Antipsychotic Agents↗

Characterization of CP-122,721; a nonpeptide antagonist of the neurokinin NK1 receptor.

CP-122,721 [(+)-(2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2 -phenylpiperidine] interacts with high affinity (pIC50 = 9.8) at the human NK1 receptor expressed in IM-9 cells. In the presence of CP-122,721, there was a reduction in Bmax of [125I]BH-SP binding with no change in affinity suggesting that CP-122,721 does not interact with the NK1 receptor in competitive manner. In an in vitro functional assay. CP-122,721 blocked SP-induced excitation of locus ceruleus cells in guinea pig brain slices with a IC50 value of 7 nM. In vivo, CP-122,721 potently blocked plasma extravasation in guinea pig lung elicited by aerosolized capsaicin (1 mM) with an ID50 = 0.01 mg/kg, p.o. Orally administered CP-122,721 antagonized Sar9, Met (O2)11-SP-induced locomotor activity in guinea pigs with an ID50 = 0.2 mg/kg suggesting good entry into the central nervous system. In addition, consistent with insurmountable blockade observed in vitro, CP-122,721 (0.01, 0.03 0.3 mg/kg, p.o.) produced a rightward shift in the dose response curve for SP-induced hypotension in the awake dog that was accompanied by a decrease in the maximal response. Thus, in vitro and in vivo CP-122,721 appears to behave functionally as a non-competitive antagonist producing an insurmountable blockade of the actions of SP.

Animals↗

5-Phenyl-3-ureidobenzazepin-2-ones as cholecystokinin-B receptor antagonists.

A series of 5-phenyl-3-ureidobenzazepin-2-one cholecystokinin-B (CCK-B) receptor antagonists was synthesized using Beckmann ring expansion of a suitable 4-phenyl-1-tetralone as a key step. Structure-activity relationship studies revealed the importance of the 5-phenyl group for potent and selective CCK-B affinity. Addition of an 8-methyl substituent and resolution provided the potent (CCK-B IC50 = 0.48 nM) CCK-B antagonist 4. The role of the 5-phenyl group as part of a "privileged structure" for high-affinity receptor antagonism is discussed.

Animals↗

Consequences of the t(14;18) chromosomal translocation in follicular lymphoma: deregulated expression of a chimeric and mutated BCL-2 gene.

The t(14;18) chromosomal translocation of human follicular lymphoma recombines the candidate transforming gene bcl-2, located at 18q21, with the immunoglobulin (Ig) H-chain joining region (JH) at 14q32. To elucidate the consequences of this translocation, we cloned bcl-2 cDNAs from a pre-B cell line (Nall-1) and a t(14;18) lymphoma cell line (SU-DHL-6) and compared these sequences with their genomic counterparts. These studies revealed the complexity of bcl-2 gene expression in which six potential polyadenylation signals in exon 3 and two different 5' exons (exons 1 and 2) and promoters are alternatively used to generate different sized bcl-2 mRNAs. A single open reading frame (ORF), at the junction of exons 2 and 3, predicts a 239 amino acid, 26 kD protein. Most chromosome 18 breakpoints cluster within a 150 bp region of exon 3. In SU-DHL-6 the t(14;18) translocation juxtaposes a truncated bcl-2 gene with J6 in a tail-to-head configuration, resulting in the deregulated expression of chimeric bcl-2/Ig transcripts. Importantly, the SU-DHL-6 bcl-2 cDNA also contained several point mutations in the ORF, two of which altered the primary amino acid sequence. The deregulated expression of an altered bcl-2 gene may play a critical role in the disordered growth and differentiation of follicular B cell lymphoma.

Amino Acid Sequence↗

Transcription mapping of the varicella-zoster virus genome.

RNA was isolated from varicella-zoster virus-infected Flow 5000 cells (diploid fibroblasts) at late times after infection. With the use of overlapping DNA probes representing all regions of the varicella-zoster genome, an extensive Northern blot analysis of the RNA was carried out. The analysis revealed at least 58 discrete transcripts ranging in size from approximately 0.8 to 6.5 kilobases. RNAs were found to be homologous to all probes used except for those mapping at approximately map unit 0.3, where no RNA transcripts could be detected. Comparison of the sizes and locations of RNA transcripts mapping in the right-hand ends of the varicella-zoster virus and the herpes simplex virus DNAs shows a number of striking analogies, suggesting their similar genomic organization.

Chromosome Mapping↗

Fetal lung liquid absorption and alveolar epithelial solute permeability in surfactant deficient, breathing fetal lambs.

The absorption of liquid volume and radiolabeled tracer solutes from the lungs of premature lambs was investigated during the first hours of ventilation. Exteriorized lambs, 133-141 d gestation, with intact umbilical circulation had [131I]albumin and [125I]cytochrome C added to the fetal lung liquid before breathing, and, additionally, [57Co]cyanocobalamin added to the remaining alveolar liquid after 20, 60, and 120 min of ventilation. Alveolar liquid was rapidly absorbed from the alveolar space, averaging more than 75% absorption in the first hour whether they breathed spontaneously or were ventilated. All animals absorbed proteins and water at the same rate as water during the first 20 min of breathing. Older, spontaneously breathing lambs released more surfactant into the alveolar space (302 +/- 82 microM) than younger ventilated animals (92 +/- 32 microM). After the first 20 min of breathing, older animals no longer absorbed [131I]albumin and [125I]cytochrome C, and at 4 h had near normal lung wet:dry weight ratio, 5.7 +/- 0.2. Younger animals continued to absorb [131I]albumin and [125I]cytochrome C as rapidly or more rapidly than liquid, and after 4 h had retained liquid in the lung wet:dry weight ratio 6.3 +/- 0.2. Alveolar surfactant appears able to alter the solute permeability of ventilated premature lung and the clearance of the fetal liquid from the lungs.

Absorption↗

Combined application of excitatory amino acids and substance P produces long-lasting changes in responses of primate spinothalamic tract neurons.

Sensitization of dorsal horn neurons following injury may underlie the generation of secondary hyperalgesia and so the chemical basis of sensitization is now receiving considerable attention. The present study used microiontophoretic applications of excitatory amino acids (EAA's) and substance P (SP) to test their roles in the sensitization of primate spinothalamic tract (STT) neurons. Of 70 STT cells examined in laminae I-VI of the dorsal horn, 40 showed an increase in responses to one or more EAA's following their co-application with SP. The increased responses were usually specific to either N-methyl-D-aspartate (NMDA) or to the non-NMDA agonists, quisqualate (QUIS) or D,L-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA). The enhancement of EAA responses was long-lasting (> 15 min) in 18 cases, was accompanied by similarly long-lasting increases in responses to mechanical stimulation of the receptive field in 14 cases and was accompanied by an increase in responses to either glutamate (Glu) or aspartate (Asp) in eleven cases. A global decrease in all EAA responses tested was produced in 26 other STT neurons. The inhibition, unlike the increases, was generalized to both NMDA and non-NMDA ligands, was long-lasting in only six cases and was never accompanied by a change in the responses to mechanical stimuli. The excitatory and inhibitory effects of SP on the responses to NMDA were uniformly reversed by the NK-1 receptor selective antagonist, CP96345. In contrast, only the inhibitory effects of SP on the responses to QUIS or AMPA were reversed by CP96345. The long-lasting enhancement of EAA responses by SP may follow the combined synaptic release of the natural ligands in vivo, resulting in the sensitization of dorsal horn neurons and secondary hyperalgesia. However, the reductions in EAA responses produced by SP are problematic for this hypothesis and need further elucidation.

Amino Acids↗

Ultrasonic diagnosis of ovarian cysts in ten guinea pigs.

Ten guinea pigs with an ovarian cyst had clinical signs of anorexia, alopecia, or depression. Ultrasonographic features of the 2- to 3-cm diameter fluid-filled cysts included compartmentalization and connection to the ovary. In two animals, a unilateral cyst was present, and in two others, the cysts were bilateral. Diagnosis of the disease by plain radiography is difficult because of the similar opacity of ovarian cysts, abdominal neoplasms, and trichobezoars.

Animals↗