Cepharanthine induces the proliferation of human dermal papilla cells and stimulates vascular endothelial growth factor expression through increased intracellular calcium mobilization and hypoxia-inducible factor activation.

BACKGROUND: Cepharanthine (CEP), a compound extracted from the vine Stephania cephalantha, is commonly prescribed to treat alopecia areata; however, the scientific evidence for its efficacy is limited. AIM: To investigate the effect of CEP and its structural analogues on human hair growth in vitro. METHODS: The effects of CEP and three of its structural analogues on the proliferation of human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs) were investigated. Their effects on vascular endothelial growth factor (VEGF) expression were also assessed by real-time PCR. Activation of pathways leading to VEGF expression, such as intracellular Ca2+ mobilization and hypoxia-inducible factor (HIF) expression, was also characterized. RESULTS: CEP and two of its structural analogues significantly stimulated the growth of hDPCs but not hORSCs. Moreover, CEP and all three structural analogues significantly induced the expression of VEGF in hDPCs. CEP increased the intracellular Ca2+ concentration in hDPCs. CEP also increased the expression of HIF-1α and HIF-2α and induced the expression of HIF-responsive genes in hDPCs, even under normoxia. CONCLUSIONS: These results suggest that CEP and its structural analogues have the potential to restore hair growth by promoting the proliferation of hDPCs and increasing their expression of VEGF.

Electrophysiology in diagnosis and management of neuropathic pain.

Electrophysiological techniques demonstrate abnormalities in somatosensory transmission, hence providing objective evidence of 'somatosensory lesion or disease' which is crucial to the diagnosis of neuropathic pain (NP). Since most instances of NP result from damage to thermo-nociceptive pathways (thin fibres and spino-thalamo-cortical systems), specific activation of these is critical to ensure diagnostic accuracy. This is currently achieved using laser pulses or contact heat stimuli, and in a near future probably also with contact cold and intra-epidermal low-intensity currents. Standard electrical stimuli, although of lesser diagnostic yield, are useful when large and small fibres are affected together. Nociceptive evoked potentials to laser (LEPs) and contact heat (CHEPs) have shown adequate sensitivity and specificity to be of clinical use in the differential diagnosis of NP, in conditions involving Aδ of C-fibres and spino-thalamo-cortical pathways. LEPs have also a role in the detection of patients at risk of developing central post-stroke pain after brainstem, thalamic or cortical injury. Cognitive cortical responses and autonomic reactions (sympathetic skin responses) reflect pain-related arousal and can document objectively positive symptoms such as allodynia and hyperalgesia. They are of help in the differential diagnosis of somatisation disorders, by discriminating conscious simulation (malingering) from conversive sensory loss. The electrophysiological approach to patients suspected, or at risk, of NP is a cost-effective procedure that should never be absent in the diagnostic armamentarium of pain clinics.

Semiology of insular lobe seizures.

After the early attempts of intra-operative electrocorticography and insulectomy in the 1950s, the notion of insular lobe seizures was largely forgotten for decades. It is only since the late 1990s that the recent technique of stereo-electroencephalography (SEEG) enabled preoperative diagnosis of insular origin seizures and thus gave rise to a renewed interest for this ill-defined electroclinical entity. Owing to the multiple functional roles of insula and its extensive connectivity with adjacent as well as distant brain structures, insular lobe seizures present with a combination or series of diverse subjective and objective symptoms. In this review, we summarize current knowledge on the semiology of insular origin seizures. The following two distinct forms of clinical presentation have been recognized: 1) Seizures with predominant insulo-perisylvian symptoms, most notably paraesthesia and cervico-laryngeal discomfort. The former typically involves a large/bilateral cutaneous territory and can be perceived as cold, hot, or painful sensations. The latter ranges from slight dyspnea to strong sensation of strangulation. Other symptoms include epigastric discomfort/nausea, hypersalivation, auditory, vestibular, gustatory, and aphasic symptoms. 2) Nocturnal hyperkinetic seizures with/without tonic elevation of upper limbs, masquerading as fronto-mesial seizures. Patients are usually not fully aware of their symptoms despite preserved contact and organized behavior to others. Ipsilateral eye blinking can be observed. These two patterns often occur in succession or simultaneously. This characteristic combination and progression of ictal symptoms orients us strongly towards an insular origin of seizure, a better understanding of which is a crucial key to further optimize modern SEEG strategy.

Hepatitis E virus in donor plasma collected in Japan.

BACKGROUND AND OBJECTIVES: Human hepatitis E virus (HEV) is prevalent worldwide. Iatrogenic HEV has recently been identified based on the reports of transfusion-transmitted cases. The detection rate of HEV-RNA and seroprevalence of HEV-IgG/IgM have been regionally evaluated in Japan, and donor plasma collected in Hokkaido is currently screened by nucleic acid amplification testing. However, the detection rate of HEV-RNA in blood donors in Japan outside of Hokkaido has not been reported. MATERIALS AND METHODS: A total of 620 140 qualified donor plasma samples from Japanese regions excluding Hokkaido were tested for HEV-RNA (pools of 50 or 500) between 2004 and 2014. HEV-RNA-positive plasma bags were identified, and the HEV viral load, genotype and anti-HEV immunoglobulin (Ig)G/IgM were evaluated. RESULTS: The detection rate of HEV-RNA (pools of 50) was 1/15 075 and higher in eastern than in western Japan. All 36 HEV-RNA-positive samples were genotype 3 with viral load ranging from <1·69 to 7·22 log10 copies/ml. CONCLUSIONS: Our detection rate of HEV-RNA in donor populations in Japan outside Hokkaido (1/15 075 donations) is generally lower than reported in Europe and lower than previously reported for Hokkaido (1/8173 donations). As methods varied, we cannot exclude that these differences are reflective of differing RNA detection limits. In contrast to Hokkaido where genotype 4 has been reported among blood donations, all our positive donations were genotype 3, which is less pathogenic.

Randomized phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations: NEJ005/TCOG0902.

BACKGROUND: The first-line combination of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and platinum-based doublet chemotherapy has not been sufficiently evaluated for patients with EGFR-mutant non-small cell lung cancer (NSCLC). This randomized phase II study was designed to select a combination regimen for phase III evaluation. PATIENTS AND METHODS: Chemotherapy-naïve patients with advanced non-squamous, EGFR-mutant NSCLC were randomly assigned to receive either a concurrent or a sequential alternating regimen with gefitinib (250 mg) and carboplatin/pemetrexed [area under the curve (AUC) = 6 and 500 mg/m(2); 3-weekly]. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), response, and safety. RESULTS: All 80 patients enrolled were eligible and assessable for efficacy (41 and 39 patients in the concurrent and sequential alternating regimen groups, respectively). Median PFS was 18.3 months for the concurrent regimen and 15.3 months for the sequential alternating regimen [hazard ratio (HR) 0.71 (0.42-1.20), P = 0.20]. Although OS data are immature (16 and 24 death events), median survival times were 41.9 and 30.7 months in the concurrent and sequential alternating regimen groups, respectively [HR 0.51 (0.26-0.99); P = 0.042]. Response rates were similar in both groups (87.8% and 84.6%). Hematological and non-hematological adverse events were common and reversible; interstitial lung disease was neither frequent nor fatal (two cases in each group; 5% of all patients). CONCLUSION: This is the first randomized study to investigate the efficacy of combinational EGFR-TKI and chemotherapy in the EGFR-mutated setting. Both regimens had promising efficacy with predictable toxicities, although concurrent regimens might provide better OS. The concurrent regimen was chosen to compare with gefitinib monotherapy in our ongoing phase III study. CLINICAL TRIALS REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN C000002789).

Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002).

BACKGROUND: NEJ002 study, comparing gefitinib with carboplatin (CBDCA) and paclitaxel (PTX; Taxol) as the first-line treatment for advanced non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, previously reported superiority of gefitinib over CBDCA/PTX on progression-free survival (PFS). Subsequent analysis was carried out mainly regarding overall survival (OS). MATERIALS AND METHODS: For all 228 patients in NEJ002, survival data were updated in December, 2010. Detailed information regarding subsequent chemotherapy after the protocol treatment was also assessed retrospectively and the impact of some key drugs on OS was evaluated. RESULTS: The median survival time (MST) was 27.7 months for the gefitinib group, and was 26.6 months for the CBDCA/PTX group (HR, 0.887; P=0.483). The OS of patients who received platinum throughout their treatment (n=186) was not statistically different from that of patients who never received platinum (n=40). The MST of patients treated with gefitinib, platinum, and pemetrexed (PEM) or docetaxel (DOC, Taxotere; n=76) was around 3 years. CONCLUSIONS: No significant difference in OS was observed between gefitinib and CBDCA/PTX in the NEJ002 study, probably due to a high crossover use of gefitinib in the CBDCA/PTX group. Considering the many benefits and the risk of missing an opportunity to use the most effective agent for EGFR-mutated NSCLC, the first-line gefitinib is strongly recommended.

Laparoscopic cholecystectomy using the subserosal layer dissection technique in dogs: 34 cases (2015-2021).

OBJECTIVES: To describe a standardised subserosal layer dissection technique and evaluate its outcomes in canine laparoscopic cholecystectomy. MATERIALS AND METHODS: Medical records of dogs undergoing laparoscopic cholecystectomy using the standardised subserosal layer dissection technique for the treatment of cholecystolithiasis, cholecystitis, and gall bladder mucocele at a single veterinary hospital from January 2015 to September 2021 were extracted. Operative time, subserosal layer dissection achievement rate, open conversion rate, and complication rate were evaluated. RESULTS: Thirty-four dogs were included. The most common preoperative diagnosis was cholecystolithiasis (n=29). Operative time was 190 minutes (range: 110 to 330 minutes). Subserosal layer dissection of more than 90% of the gall bladder bed was achieved in 27 (79%) dogs. Conversion to open surgery was required in three (8.8%) dogs. There were no cases of intraoperative bleeding, bile duct injury, or reoperation. CLINICAL SIGNIFICANCE: This study showed that laparoscopic cholecystectomy using the standardised subserosal layer dissection technique could be performed successfully in dogs. Future prospective clinical studies are needed to determine safety and effectiveness of this technique compared to standard techniques.

An evaluation study of EGFR mutation tests utilized for non-small-cell lung cancer in the diagnostic setting.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is predictive for the efficacy of EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer (NSCLC) treatment. We evaluated the performance, sensitivity, and concordance between five EGFR tests. MATERIALS AND METHODS: DNA admixtures (n = 34; 1%-50% mutant plasmid DNA) and samples from NSCLC patients [116 formalin-fixed paraffin-embedded (FFPE) tissue, 29 matched bronchofiberscopic brushing (BB) cytology, and 20 additional pleural effusion (PE) cytology samples] were analyzed. EGFR mutation tests were PCR-Invader, peptide nucleic acid-locked nucleic acid PCR clamp, direct sequencing, Cycleave, and Scorpion Amplification Refractory Mutation System (ARMS). Analysis success, mutation status, and concordance rates were assessed. RESULTS: All tests except direct sequencing detected four mutation types at ≥1% mutant DNA. Analysis success rates were 91.4%-100% (FFPE) and 100% (BB and PE cytology), respectively. Inter-assay concordance rates of successfully analyzed samples were 94.3%-100% (FFPE; kappa coefficients: 0.88-1.00), 93.1%-100% (BB cytology; 0.86-1.00), and 85.0%-100% (PE cytology; 0.70-1.00), and 93.1%-96.6% (0.86-0.93) between BB cytology and matched FFPE. CONCLUSIONS: All EGFR assays carried out comparably in the analysis of FFPE and cytology samples. Cytology-derived DNA is a viable alternative to FFPE samples for analyzing EGFR mutations.

Changes in immune system and intestinal bacteria of cows during the transition period.

High-yield dairy cows need high energy feed during periods of increased milk production. The transitional feeding to high energy feed increases the risk of developing a variety of metabolic disorders. Here, five Holstein cows were fed a four-stage feeding protocol (3 weeks for each stage) ranging from 54.9 to 73.7% total digestive nutrients (TDN). The purpose of the study was to investigate the effect of lactic acid bacteria on high-energy-fed cows associated with transitional feeding, and to evaluate the effects of probiotics on intestinal bacterial changes and inflammatory responses. Three feed transition periods were established for five cows, and Lactobacillus plantarum RGU-LP1 (LP1) was fed as a probiotic during the high-energy feeding period. The number of lymphocyte subsets such as CD3-, CD4-, and CD8 positive cells decreased in response to the high energy feed. Lipopolysaccharide (LPS)-induced cytokine (IL-1ß and IL-2) gene expression in peripheral blood mononuclear cells (PBMCs) was shown to increase in those animals receiving the high energy feed. However, supplementation with LP1 resulted in an increase in the number of lymphocyte subsets and the expression of IL-1ß and IL-2 were returned to the level at low energy diet. These results suggest that high energy diets induce inflammatory cytokine responses following LPS stimulation, and that the addition of LP1 mitigates these results by regulating the LPS-induced inflammatory reaction. Therefore, the functional lactic acid bacteria LP1 is expected to regulate inflammation resulting from high energy feeding, and this probiotic could be applied to support inflammatory regulation in high-yield dairy cows.

A case of pulmonary alveolar microlithiasis with an intragenetic deletion in SLC34A2 detected by a genome-wide SNP study.

A case of pulmonary alveolar microlithiasis occurring in an inbred family is presented. A genome-wide analysis of the patient's genomic DNA using a high-density single nucleotide polymorphism (SNP) array revealed a small intragenetic mutation at SLC34A2. The results suggest that the high-density SNP array has the power to identify a recessive disease gene(s) even in the analysis of only a single inbred patient.

p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation.

Janus kinase 2 (JAK2) V617F mutation has been regarded as the major cause of myeloproliferative disorders (MPD). However, the mechanisms of abnormal cell growth by JAK2V617F have not been elucidated. In this study, cell cycle regulatory protein expression was analyzed using JAK2V617F-Ba/F3 and mock-Ba/F3. JAK2V617F-Ba/F3, but not mock-Ba/F3, showed IL-3 independent cell growth and constitutive STATs activation. Deregulation of p27(Kip1), the cell cycle regulator at the G1 to S transition, was observed in JAK2V617F-Ba/F3 but not in mock-control. p27(Kip1) deregulation was not due to p27(Kip1) mRNA level but due to high Skp2 expression, a subunit of ubiquitin E3 ligase, through the STAT binding in the Skp2 promoter. Like JAK2V617F overexpression, constitutively active STAT5 or STAT3 induced aberrant p27(Kip1) expression of Ba/F3 cells. Similar findings were observed in BCR/ABL-transfected Ba/F3. Our results elucidate the regulatory mechanism by which JAK2V617F modulates Skp2 gene expression through the STAT transcription factors.

A novel putative tyrosine kinase receptor encoded by the eph gene.

Growth factors and their receptors are involved in the regulation of cell proliferation and also play a key role in oncogenesis. In this study, a novel putative kinase receptor gene, termed eph, has been identified and characterized by molecular cloning. Its primary structure is similar to that of tyrosine kinase receptors thus far cloned and includes a cysteine-rich region in the extracellular domain. However, other features of the sequence distinguish the eph gene product from known receptors with tyrosine kinase activity. Thus the eph protein may define a new class of these molecules. The eph gene is overexpressed in several human carcinomas, suggesting that this gene may be involved in the neoplastic process of some tumors.

A single residue in the 126-kDa protein of pepper mild mottle virus controls the severity of symptoms on infected green bell pepper plants.

Infectious cDNA clones originally derived from a mild strain of Pepper mild mottle virus were constructed by replacing residue 649, a critical point for attenuation of this virus, with all possible amino acids. All clones were infectious to pepper plants and induced a variety of symptoms, including no visible symptoms. The results of this study showed that a single amino acid mutation at residue 649 could control the function of the 126- and 183-kDa proteins, replicases with multiple roles in the life cycle of this virus.

[Integrated coronary artery bypass strategy prevents urgent pump conversion during off-pump coronary artery bypass grafting].

Urgent pump conversion during off-pump coronary artery bypass (OPCAB) results in high morbidity and mortality. We retrospectively evaluated if the peri-operative integrated strategy prevents this lethal event in our 400 consecutive OPCAB operations. The patients with preoperative cardiogenic shock and/or ventricular arrhythmias underwent on-pump coronary artery bypass grafting (CABG). All other patients (99% of total CABG) were scheduled to undergo OPCAB (n=400). Prophylactic intraaortic balloon pumping (IABP) was applied to the patients with critical (>95%) left main trunk stenosis or low (<0.35) left ventricular ejection fraction. All the patients received the deep pericardial suture, apex-traction device, suction-type stabilizer, test-clamp of target coronary arteries by micro bulldog clamp, and intra-coronary shunts. Intra-operative IABP was applied in the case of sustained ST-segment change and/or elevated pulmonary artery pressure. Pump conversion was indicated for the patients with ventricular fibrillation and/or cardiogenic shock. Two patients (0.5%) had pump conversion due to ventricular arrhythmia and sustained hypotension, respectively. These pump conversion did not result in hospital mortality. Three hospital deaths (0.7%) occurred due to non-cardiac causes. The integrated strategy using prophylactic or intra-operative IABP in OPCAB produce a low pump conversion rate even during an early period of surgeon's learning curve.

Ewing's sarcoma fusion protein, EWS/Fli-1 and Fli-1 protein induce PLD2 but not PLD1 gene expression by binding to an ETS domain of 5' promoter.

It was reported that short interfering RNA (siRNA) of EWS/Fli-1 downregulated phospholipase D (PLD)2 in Ewing's sarcoma (EWS) cell line, suggesting that PLD2 is the target of aberrant transcription factor, EWS/Fli-1. Here, we further investigated the regulation of PLD2 gene expression by EWS/Fli-1 and Fli-1 in another EWS cell line, and also in EWS/Fli-1- or Fli-1-transfected cell line. EWS/Fli-1- or Fli-1-overexpressed cells showed higher PLD2 but not PLD1 protein expression and enhanced cell proliferation as compared to mock transfectant. The treatment of these cells with 1-butanol or siRNA of PLD2 inhibited cell growth, suggesting the pivotal role of PLD in cell growth promotion. PLD2 but not PLD1 mRNA level was also increased in EWS/Fli-1 or Fli-1-transfectants. After determining the transcription initiation points, we cloned the 5' promoter of both PLD1 and PLD2 and analysed promoter activities. Results showed that EWS/Fli-1 and Fli-1 increase PLD2 gene expression by binding to an erythroblast transformation-specific domain (-126 to -120 bp from the transcription initiation site) of PLD2 promoter, which is the minimal and most powerful region. Electrophoresis mobility shift assay using truncated proteins showed that both DNA-binding domain and trans-activating domain were necessary for the enhanced gene expression of PLD2.

Interferon-beta augments eosinophil adhesion-inducing activity of endothelial cells.

Viral infections induce exacerbations of asthma. One of the earliest host responses to viral infections is the production of innate cytokines including type I interferons (IFNs), such as IFN-beta, which may act to modify airway inflammation. The objective of the present study was to investigate whether IFN-beta modifies the eosinophil adhesion-inducing activity of endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with IFN-beta for 24 h in the presence or absence of tumour necrosis factor (TNF)-alpha. Eosinophils were isolated from the peripheral blood of healthy volunteers. The ability of the IFN-beta-stimulated HUVEC monolayers to induce eosinophil adhesion was assessed according to the eosinophil peroxidase assay. Eosinophil adhesion to HUVECs was significantly augmented by IFN-beta in the presence of TNF-alpha but not in its absence. The augmented adhesion was inhibited by anti-alpha(4) integrin monoclonal antibody (mAb) or anti-beta(2) integrin mAb. IFN-beta significantly enhanced the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 on HUVECs in the presence of TNF-alpha. Interferon-beta can augment the adhesiveness of endothelial cells to eosinophils, mainly through the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. This action of interferon-beta may contribute to the intensification of airway inflammation in asthma that is associated with exacerbations induced by viral infections.

Extent of hepatitis E virus elimination is affected by stabilizers present in plasma products and pore size of nanofilters.

BACKGROUND AND OBJECTIVE: To investigate the physico-chemical properties of hepatitis E virus (HEV) with regard to inactivation/removal, we have studied four isolates with respect to sensitivity to heat during liquid/dry-heating as well as removal by nanofiltration. MATERIALS AND METHODS: Hepatitis E virus in an albumin solution or phosphate-buffered saline (PBS) was liquid-heated at 60 degrees C for a preset time. HEV in a freeze-dried fibrinogen containing stabilizers was also dry-heated at 60 or 80 degrees C for a preset time. In addition, to clarify the removal of HEV, the purified virus in PBS was filtered using several types of virus-removal filter (nanofilters) that have different pore sizes. HEV infectivity or genome equivalents before and after the treatments were assayed by a semiquantitative cell-based infectivity assay or quantitative polymerase chain reaction assay, respectively. RESULTS: Hepatitis E virus isolates in albumin solutions were inactivated slowly at 60 degrees C for 5 h and the resultant log reduction factor (LRF) was from 1.0 to > or = 2.2, whereas the virus in PBS was inactivated quickly to below the detection limit and the LRF was > or = 2.4 to > or = 3.7. The virus in a freeze dried fibrinogen containing trisodium citrate dihydrate and l-arginine hydrochloride as stabilizers was inactivated slowly and the LRF was 2.0 and 3.0, respectively, of the 72 h at 60 degrees C, but inactivated to below the detection limit within 24 h at 80 degrees C with an LRF of > or = 4.0. The virus in PBS was also confirmed as to be approximately 35 nm in diameter by nanofiltration. These results are useful for evaluating viral safety against HEV contamination in blood products. CONCLUSION: The sensitivity of HEV to heat was shown to vary greatly depending on the heating conditions. On the other hand, the HEV particles were completely removed using 20-nm nanofilters. However, each inactivation/removal step should be carefully evaluated with respect to the HEV inactivation/removal capacity, which may be influenced by processing conditions such as the stabilizers used for blood products.

Organization and chromosomal localization of the human platelet-derived endothelial cell growth factor gene.

Human platelet-derived endothelial cell growth factor (hPD-ECGF) is a novel angiogenic factor which stimulates endothelial cell growth in vitro and promotes angiogenesis in vivo. We report here the cloning and sequencing of the gene for hPD-ECGF and its flanking regions. This gene is composed of 10 exons dispersed over a 4.3-kb region. Its promoter lacks a TATA box and a CCAAT box, structures characteristic of eukaryotic promoters. Instead, six copies of potential Sp1-binding sites (GGGCGG or CCGCCC) were clustered just upstream of the transcription start sites. Southern blot analysis using genomic DNAs from several vertebrates suggested that the gene for PD-ECGF is conserved phylogenetically among vertebrates. The gene for hPD-ECGF was localized to chromosome 22 by analysis of a panel of human-rodent somatic cell hybrid lines.

Pancreatic Colloid Carcinoma in an Elderly Cat.

A 21-year-old neutered female domestic shorthaired cat was presented with a history of inappetence, vomiting and haematuria. The cat was humanely destroyed at the owner's request and a necropsy examination was performed. A 0.8 × 0.5 × 0.5 cm mass was located in the left lobe of the pancreas. The mass was gelatinous in nature and the external and cut surfaces were pale yellow in colour. Microscopically, the mass was non-capsulated and comprised an accumulation of extracellular stromal mucin containing suspended neoplastic columnar epithelial cells forming tubular structures. Immunohistochemically, these cells diffusely expressed cytokeratin (CK) AE1/AE3, CK7 and carcinoembryonic antigen and were partially positive for CK19 and trypsin, but negative for vimentin. The tumour was diagnosed as a colloid carcinoma. The clinical presentation in this case was caused by chronic renal failure complicated by secondary renal hyperparathyroidism and associated metastatic calcinosis. To the best of our knowledge, this is the first report of colloid carcinoma arising from the pancreas in a cat.