Bronchoscopic findings in dogs with bronchial vegetal foreign bodies: 84 cases (2010-2020).

OBJECTIVES: To describe endoscopic findings, foreign body location, success rate of removal and complications in dogs with bronchial vegetal foreign bodies. MATERIALS AND METHODS: The current study retrospectively evaluated the case records of dogs diagnosed with bronchial vegetal foreign bodies at a veterinary hospital centre between January 2010 and April 2020. Information retrieved included breed, sex, age, bodyweight, the season of presentation, presentation and duration of clinical signs, previous removal attempts performed by the referring veterinarian, foreign body location and endoscopic and imaging findings. RESULTS: Eighty-four cases were included. Fifty-nine dogs (70%) presented during spring and summer. Cough (77 of 84; 92%) and fever (15 of 84; 18%) were the main clinical signs. One to 10 bronchial vegetal foreign bodies were removed from each dog. Purulent exudate was observed in the ventral larynx, trachea and bronchi in 49 (65%), 61 (81%) and 71 (95%) dogs, respectively. In most cases, only the barbules of the vegetal foreign bodies were initially observed during endoscopy. The presence of large bronchial nodules or an irregular mucosal surface was a frequent finding (62 of 75; 83%). Mild bleeding was the main complication (58 of 75; 77%) of endoscopic removal, which was successful in 67 of the 84 (80%) cases. CLINICAL SIGNIFICANCE: Mucosal nodules associated with purulent material within the airways are frequent endoscopic findings in dogs with bronchial vegetal foreign bodies. Bronchoscopy is a relatively safe and useful technique for diagnosis and treatment of bronchial vegetal foreign bodies in dogs.

Extended palatoplasty as surgical treatment for nasopharyngeal stenosis in six cats.

OBJECTIVE: To describe the use of extended palatoplasty as treatment of caudal nasopharyngeal stenosis in cats. MATERIALS AND METHODS: CT was used to confirm the diagnosis in cats with clinical signs consistent with nasopharyngeal stenosis. Extended palatoplasty rostral to the tonsils using monopolar electrocautery allowed simultaneous removal of the caudal soft palate together with the stenotic area. Cats were re-evaluated 2 weeks postoperatively. Telephone interview was used to obtain long-term follow-up. RESULTS: Six domestic shorthair cats were diagnosed with nasopharyngeal stenosis, with clinical signs of snoring (n=4), stertor (n=4), nasal discharge (n=3) and sneezing (n=1). CT scan identified a soft-tissue stricture at the level of the caudal nasopharynx in all cats. Other abnormalities included bilateral rhinitis (n=3), retropharyngeal adenomegaly (n=2), unilateral sinusitis (n=1) and bilateral otitis externa with unilateral otitis media (n=1). Excision of the caudal soft palate and the entire stenotic soft-tissue membrane was successful in all six cats. No pre-, intra- or postoperative complications were observed. Short-term outcome revealed clinical improvement in all cases. Long-term outcome revealed no recurrence of clinical signs in four cats. In one cat, occasional sneezing was reported. One cat died 1 month postoperatively for reasons unrelated to the respiratory condition. CLINICAL SIGNIFICANCE: Extended palatoplasty was an effective technique to treat caudal nasopharyngeal stenosis and provide improvement of clinical signs without postoperative complications in all cases.

Endoscopic and surgical removal of oesophageal and gastric fishhook foreign bodies in 33 animals.

OBJECTIVES: To describe the location, retrieval, frequency of surgery and complications associated with fishhook foreign bodies. MATERIALS AND METHODS: Retrospective evaluation of the medical records of cats and dogs admitted between 2010 and 2016 after fishhook ingestion. RESULTS: A total of 33 cases (2 cats and 31 dogs) were included. The most common locations were the proximal oesophagus [12/33 (36%)] and stomach [11/33 (33%)]. Endoscopic retrieval was successful in 27 of 33 cases (82%); oesophageal perforation was the only recorded complication, occurring in six of 33 (18%) cases. Surgery was performed in six cases (18%), and no early complications were recorded. The survival rate was 100%. CLINICAL SIGNIFICANCE: The endoscopic removal of ingested fishhooks is highly successful. In the present study, survival to discharge was 100%, even in cases of oesophageal perforation or in cases requiring surgery.

Exogenous cdk4 overcomes reduced cdk4 RNA and inhibition of G1 progression in hematopoietic cells expressing a dominant-negative CBF - a model for overcoming inhibition of proliferation by CBF oncoproteins.

Core Binding Factor (CBF) is required for the development of definitive hematopoiesis, and the CBF oncoproteins AML1-ETO, TEL-AML1, and CBFbeta-SMMHC are commonly expressed in subsets of acute leukemia. CBFbeta-SMMHC slows the G1 to S cell cycle transition in hematopoietic cells, but the mechanism of this effect is uncertain. We have sought to determine whether inhibition of CBF-mediated trans-activation is sufficient to slow proliferation. We demonstrate that activation of KRAB-AML1-ER, a protein containing the AML1 DNA-binding domain, the KRAB repression domain, and the Estrogen receptor ligand binding domain, also slows G1, if its DNA-binding domain is intact. Also, exogenous AML1 overcame CBFbeta-SMMHC-induced inhibition of proliferation. Representational difference analysis (RDA) identified cdk4 RNA expression as an early target of KRAB-AML1 activation. Inhibition of CBF activities by KRAB-AML1-ER or CBFbeta-SMMHC rapidly reduced endogenous cdk4 mRNA levels, even in cells proliferating at or near control rates as a result of exogenous cdk4 expression. Over-expression of cdk4, especially a variant which cannot bind p16INK4a, overcame cell cycle inhibition resulting from activation of KRAB-AML1-ER, although cdk4 did not accelerate proliferation when expressed alone. These findings indicate that mutations which alter the expression of G1 regulatory proteins can overcome inhibition of proliferation by CBF oncoproteins. Oncogene (2000).

Small deletions occur in highly conserved regions of the LAZ3/BCL6 major translocation cluster in one case of non-Hodgkin's lymphoma without 3q27 translocation.

The LAZ3/BCL6 gene encoding a Zinc-finger nuclear protein is altered in Non-Hodgkin's Lymphomas (NHLs) by translocations, mutations and/or deletions clustered in its 5' non coding region, in a 3.3 Kbp EcoRI fragment which thus defines the Major Translocation Cluster (MTC). In the present study, we describe at the molecular level the deletions found in the MTC of two (NHL) cases using, (i) DNA obtained from a patient (GUI) with a monosomy 3 and three microdeletions of 101, 22, 25 bp in its unique untranslocated 3q27 allele; (ii) a cell line derived from a patient (VAL) carrying a t(3;4) (q27;p11) translocation and a 2.4 Kbp deletion in the untranslocated allele. As the MTC is recurrently subject to alterations, we have cloned and sequenced the murine equivalent of the human MTC and promoter region in an attempt to identify sequences well conserved in mammals that may be thus important for the LAZ3/BCL6 gene regulation. We show that the human and mouse 5' upstream regions of the LAZ3/BCL6 gene although mainly intronic share a particularly high homology of 79% on the overall sequence. Strikingly, the small sequences which are deleted in patient (GUI) are highly conserved (81%, 100% and 92% respectively). Furthermore, they may play a role in the pathogenesis since proteins prepared from B cell lines and HeLa nuclear extracts bind to these sequences in gel retardation assays. Although a large part of this region is intronic, the high conservation of its sequence and the frequency of alterations in NHLs suggest that they are likely to be significant for the regulation of the LAZ3/BCL6 gene.

Multiple domains participate in distance-independent LAZ3/BCL6-mediated transcriptional repression.

The LAZ3/BCL6 gene implicated in diffuse large cell lymphomas encodes a transcriptional repressor containing Krüppel-fike zinc fingers. It harbours at its N-terminus a conserved protein/protein interaction motif, the BTB/POZ domain, which is also an autonomous transcriptional repression domain. We demonstrate here using several GAL4-LAZ3/BCL6 chimeras that the BTB/POZ domain plays an important but not exclusive role as its deletion gives rise to a GAL4 chimera that mediates significant, albeit reduced, transcriptional repression. Moreover, the repressive effect mediated either by LAZ3/BCL6 or by the isolated domains occurs with unaltered efficiency even at long distance (1.6 Kbp), ruling out steric hindrance mechanisms. Finally, though the absence of a TATA box appears to weaken this activity, it is largely promoter independent. Taken together, our results demonstrate that multiple domains participate in the promoter and distance-independent LAZ3/BCL6-mediated transcriptional repression.

The LAZ3/BCL6 oncogene encodes a sequence-specific transcriptional inhibitor: a novel function for the BTB/POZ domain as an autonomous repressing domain.

Rearrangements and mutations of the LAZ3/BCL6 gene are the most frequent events associated with diffuse large-cell lymphoma, a particular class of non-Hodgkin's lymphomas. This gene encodes a putative regulatory protein with six COOH-terminal Krüppel-like zinc fingers and a NH2-terminal hydrophobic region, the so-called BTB/POZ domain, which mediates homo- as well as heterotypic interactions in other related proteins. Recently, a consensus binding sequence has been defined using the isolated LAZ3/BCL6 zinc finger region produced in bacteria. To understand the normal and oncogenic functions of LAZ3/BCL6, we examined its properties as a transcription factor. We thus demonstrated that its full-length product binds to the same consensus sequence, although the BTB/POZ domain decreases this activity, at least in vitro. In transient transfection experiments, the LAZ3/BCL6 protein exerts a repressive effect, both as a wild-type protein on its own target sequence and as a GAL-4 fusion protein. Furthermore, our results indicate that the BTB/POZ domain plays a prominent role in the mediation of this activity. Indeed, on the LAZ3/BCL6 cognate sequence, deletion of the BTB/POZ domain diminishes the repressive function. Conversely, as a GAL-4 chimera, the isolated LAZ3/BCL6 BTB/POZ domain appears nearly as efficient as the entire protein at inducing transcriptional repression. Taken together, these findings demonstrate that the LAZ3/BCL6 is a sequence-specific transcriptional repressor and point to a novel function for the BTB/POZ region, at least in LAZ3/BCL6, as an autonomous transcriptional inhibitory domain.