Ki Chang Lee

N-hexanoyl chitosan-stabilized magnetic nanoparticles: enhancement of adenoviral-mediated gene expression both in vitro and in vivo

We developed hexanoyl chloride-modified chitosan (Nac-6) stabilized iron oxide nanoparticles (Nac-6-IOPs) as magnetic nanoparticles for viral gene (Ad/LacZ) delivery via magnetofection. This vector, Nac-6-IOPs/Ad/LacZ, binds to K562 cells in the presence of external magnetic fields and results in enhanced expression of the transgene in those cells that do not exhibit the coxsackie-adenovirus receptor (CAR). Our results demonstrate that Nac-6-IOPs/Ad/LacZ is able to transduce K562 cells specifically with reduced infection of CAR- cells. The dramatic enhancement in intracellular trafficking of the adenovirus without genetically modified vesicles can lead to enhanced nuclear transfer, especially in CAR- cells. In vivo magnetofection results also clearly demonstrated that the present Nac-6-IOPs could be applied in other cell lines. Whether cells or organs, in the presence of magnetic fields Nac-6-IOPs/Ad/LacZ has high transduction efficiency. The newly formulated Nac-6-IOPs, introduced by magnetofection, provide a high-throughput gene screening both in vitro and in vivo.

The antitumor effect and hepatotoxicity of a hexokinase II inhibitor 3-bromopyruvate: in vivo investigation of intraarterial administration in a rabbit VX2 hepatoma model.

Objective The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. Materials and Methods This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. Results The tumor necrosis rate was significantly higher in the high dose group (93% ± 7.6 [mean ± SD]) than that in the control group (48% ± 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% ± 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% ± 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Conclusion Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.

Cytologic and immunohistochemical characterization of a primitive neuroectodermal tumor in the brain of a dog

A 6-year-old intact female Pointer dog was presented for evaluation of acute onset of ataxia, circling, and head tilt. Neurologic assessment revealed overall decreased postural reaction, left-sided hemiparesis with incoordination, rigidity of fore- and hindlimbs, strabismus of the right eye, and bilateral horizontal nystagmus. Using magnetic resonance imaging, a mass lesion was identified in the cerebrum adjacent to the left side of the cerebellum compressing the brain stem ventrally. The mass was incompletely resected, and during surgery fine-needle aspiration and biopsy of the mass were performed. Cytologically, smears were highly cellular and contained predominantly small to medium-sized discrete round cells with high nuclear to cytoplasmic ratios and round nuclei with rare deep clefts or indentation, smooth chromatin, and indistinct nucleoli. Numerous cytoplasmic fragments were noted in the background. The primary diagnosis was lymphoma; other differential diagnoses included neuroendocrine tumor and poorly differentiated tumor of neural origin. The histologic diagnosis was lymphoma, and the lesion was presumed to be metastatic. On immunohistochemical analysis, the cells expressed neither CD3 nor CD79a. Re-examination of the histologic section revealed disorganized sheets of cells with multifocal palisading and perivascular arrangements of rosette-like structures. An expanded panel of antibodies to vimentin, cytokeratin, glial fibrillary acid protein (GFAP), neuron-specific enolase (NSE), synaptophysin (SYN), S-100, and CD45 was applied to histologic sections. Neoplastic cells were immunoreactive for vimentin, NSE, and S-100. Based on the histologic appearance and immunophenotype of the tumor, a diagnosis of primitive neuroectodermal tumor (PNET) was made. PNET, although rare in dogs, should be considered as a differential diagnosis for round cell tumors in the brain.

Assessment of Lymph Node Metastases by Contrast-Enhanced MR Imaging in a Head and Neck Cancer Model

Objective We wanted to investigate the accuracy of contrast-enhanced MR imaging for the detection of lymph node metastases in a head and neck cancer rabbit model. Materials and Methods The metastatic lymph node model we used was created by inoculating VX2 tumors into the auricles of six New Zealand White rabbits. T1-weighted MR images were obtained before and after injecting gadopentetate dimeglumine at three weeks after tumor cell inoculation. The sizes, signal intensity ratios (i.e., the postcontrast signal intensities of the affected nodes relative to the adjacent muscle) and the enhancement patterns of 36 regional lymph nodes (parotid and caudal mandibular nodes) were evaluated on MR images and then compared with the histopathologic findings. Results No statistical difference was found between the sizes of 12 metastatic (10.5±3.2 mm) and 24 hyperplastic (8.0±3.6 mm) lymph nodes (p > 0.05). On the contrast-enhanced T1-weighted MR images, nine metastatic and four hyperplastic lymph nodes had peripheral high and central low signal intensity, whereas three metastatic and 20 hyperplastic lymph nodes had homogeneous high signal intensity. Using a signal intensity ratio less than one as a diagnostic criterion for a metastatic lymph node, the sensitivity, specificity and positive and negative predictive values of the enhanced MR images were 75% (9/12), 83% (20/24), 69% (9/13) and 87% (20/23), respectively, with areas under receiver-operating-characteristic curve values of 0.81. Conclusion This experimental study confirms that metastatic and hyperplastic lymph nodes can be differentiated using MR images on the basis of the contrast uptake patterns, but that they cannot be differentiated using any particular size criteria.

Successful treatment of an unusually large corneal epithelial inclusion cyst using equine amniotic membrane in a dog.

A 10-year-old intact male Yorkshire Terrier was referred for investigation of a large raised and nonpainful corneal lesion oculus dexter. Clinical examination revealed a pale, translucent corneal mass, which occupied half of the corneal surface and measured 11 mm x 11 mm x 13 mm. The mass was removed by superficial keratectomy and equine amniotic membrane (AM) was transplanted into the large corneal defect to cover the wound and provide tectonic support for the remaining cornea. The mass was histologically confirmed as a corneal epithelial inclusion cyst. There was no evidence of recurrence or complication at the surgical site 100 days postoperatively. Corneal epithelial inclusion cysts are uncommon in dogs. Although superficial keratectomy is the recommended treatment for corneal inclusion cyst, the combination of superficial keratectomy and AM transplantation had to be considered as an alternative for repair of large corneal defects. This is the first case report of the combined application of AM and superficial keratectomy to successfully treat a corneal inclusion cyst in a dog.

Diagnostic imaging characteristics of ureteral pseudodiverticulosis in three dogs

Ureteral pseudodiverticulosis is rarely reported in veterinary medicine. This case study aimed to describe the radiographic, ultrasonographic and computed tomographic findings for dogs with radiologically confirmed ureteral pseudodiverticulosis. Three dogs met the inclusion criteria. Radiographic findings included multiple small, round-shaped mineral opacities located around the periphery of the ureters (3/3), and multiple contrast medium-filled outpouchings that appeared and disappeared when the contrast medium washed in and out on intravenous excretory urography (2/3). The outpouchings were approximately 1 mm in diameter. In the ultrasonographic images, the mineral foci were located adjacent to the ureter, but not within the ureteral lumen (1/3). Contrast-enhanced CT findings were similar to those of excretory urography (2/3). Ureteral pseudodiverticulosis should be considered in the differential diagnosis for old-aged and small-breed dogs with radiopaque materials along the ureteral pathways; excretory urography or contrast-enhanced CT are recommended for a more definitive imaging diagnosis.

Restrainer exposure to scatter radiation in practical small animal radiography measured using thermoluminescent dosimeters

This study was aimed at estimating restrainer exposure to scatter radiation in veterinary radiography using thermoluminescent dosimeters (TLDs) in different positions, and at different anatomic regions. A prospective study was conducted to measure exposure dose of two restrainers: A (cathode side) and B (anode side), and an observer C (at a 1-meter distance from the X-ray table) over two months. Protective devices included panorama mask, thyroid shield and arm shield. TLDs were placed on the inside and outside of the protective gear at five different anatomic sites (eye, thyroid, breast, gonad and arm). The study data consisted of 778 exposures, 82 patients (78 dogs, four cats), a mean kVp of 58.7 and a mean mAs of 11.4. The doses (outside the shield/inside the shield, in mSv) measured by restrainers A, B and C were eye (3.04/0.42), (2.29/0.17), (0.55/0.01), thyroid (2.93/0.01), (1.97/0.01), (0.19/0.01), breast (1.01/0.04), (0.73/0.01), (0.32/0.01), gonad (0.07/0.01), (0.01/0.01), (0.16/0.01) and arm (2.81/1.43), (1.17/0.01), (0.08/0.01), respectively. This study describes the extent of occupational radiation exposure in small animal radiography. The exposure dose for eyes outside lead protection showed the highest value in all participants. With lead protection, the reduction in the exposure dose of eyes was significant (A: 86%, B: 93%, C: 98%), and the highest reduction was 99% in the thyroid region. These results suggest the necessity of radiation shields in manual restraint, particularly for eye protection.

Feasibility of dental panoramic radiography for dental arch evaluation in small animals

The purpose of this study was to evaluate the feasibility of dental panoramic radiography for dental arch evaluation in small animals. The dental arches of four Beagles, one Shih Tzu dog, and three Korean shorthaired cats were radiographed using human panoramic X-rays. All animals were under general anaesthesia during the examination. The animals’ heads were placed horizontal to the panoramic device, just as a human’s head is placed in panoramic dental assessments. All animals were evaluated with an open and closed mouth view (human view). In the closed mouth view, the animal was provided a bite blocker for proper placement of the oral cavity. The open mouth view angle was approximately 30–45°. The maxilla and mandible were held in position with radiolucent 3M tape. The standard scoring measurement was performed based on visibility of the tooth root and the sharpness of the dento-alveolar margin. No significant differences in scoring were noticed between the two positions. The visibility of teeth roots in Beagles was far better than that in the Shih Tzu dogs and two Korean short-haired cats. In addition, the Beagle series showed sharp dento-alveolar margin scores. These results suggest that human panoramic dental X-rays represent a possible dental evaluation tool for animals with large skulls.

Atypical radiographic features of multiple myeloma in a dog: a case report

A 12-year-old castrated male miniature pinscher dog presented with right forelimb lameness. An expansile osteolytic lesion of the right humerus was conspicuous on right forelimb radiographs. Thoracic and abdominal radiographs showed multiple lytic bone lesions on the right scapula, ribs, vertebrae, femurs and pelvis. Additionally, an expansile osteolytic lesion was observed in two thoracic vertebrae and two ribs. Many plasma cells were identified on fine-needle aspiration of the right humerus expansile osteolytic lesion, and monoclonal gammopathy consistent with multiple myeloma was confirmed on serum protein electrophoresis. The expansile osteolytic lesion, an extraordinary radiographic feature of multiple myeloma in dogs, should be considered as a possible radiographic finding of multiple myeloma.

A challenging radiographic diagnosis – extraluminal leiomyoma of the oesophagus in a small-sized dog: a case report

An 11-year-old, intact male Maltese dog presented with a history of vomiting and regurgitation. On plain radiographs, a caudodorsal thoracic mass was identified, and there were no radiographic signs frequently associated with an oesophageal mass. An oesophagram with fluoroscopy showed no classical signs of an oesophageal mass such as an irregular mucosal surface, a filling defect, or decreased ability of the lumen to pass contrast medium through the oesophageal lumen. A mass of pulmonary or mediastinal origin rather than of oesophageal origin was suggested. During the operation for mass removal, a gross connection between the suspected mass and the adventitia of the distal oesophagus was identified; thus, excision of the extraluminal mass was performed from the outer oesophageal wall. Histopathology confirmed the mass to be an oesophageal leiomyoma. This case highlights that the differentiation of an extraluminal oesophageal mass from other masses of mediastinal or lung origin can be challenging with radiographs and oesophagram alone. Even when the radiographic signs are not suggestive of an oesophageal mass, an extraluminal oesophageal mass should be considered.