Kiichi Kanayama

Suppressive role of leukocyte cell–derived chemotaxin 2 in mouse anti–type II collagen antibody–induced arthritis

OBJECTIVE We previously reported that the Val58Ile polymorphism of the leukocyte cell-derived chemotaxin 2 gene (LECT2) is associated with the severity of rheumatoid arthritis (RA). To define the role of LECT2 in inflammatory arthritides, we investigated the development of collagen antibody-induced arthritis (CAIA) in LECT2-deficient (LECT2(-/-)) mice. METHODS CAIA was induced in mice by administering anti-type II collagen antibodies followed by lipopolysaccharide. Daily assessment of hind paw swelling was used to monitor the development of arthritis. The histopathologic features and expression of inflammatory cytokines were also analyzed. We confirmed the role of LECT2 by introducing a LECT2 expression vector into LECT2(-/-) mice, using a hydrodynamic gene transfer method. RESULTS Arthritis in LECT2(-/-) mice was significantly exacerbated compared with that in wild-type (WT) controls. Histopathologic assessment of the tarsal joints showed that inflammation and erosion of cartilage and bone in LECT2(-/-) mice were more severe than that in controls. Interleukin-1beta (IL-1beta), IL-6, and certain chemokines were present at significantly higher levels in the arthritic hind paws of LECT2(-/-) mice. In contrast, the amount of LECT2 in the serum and locally in the hind paws was higher in arthritic WT mice. Finally, hydrodynamic gene transfer experiments revealed that the severity of arthritis was reduced by the systemic expression of exogenous mouse LECT2 protein in LECT2(-/-) mice. CONCLUSION These results strongly suggest that LECT2 directly suppresses the development of CAIA. Manipulation of LECT2 might provide a rationale for novel therapeutic approaches to the treatment of inflammatory arthritides such as RA.

Pregnancy by Means of Tubal Insemination and Subsequent Spontaneous Pregnancy in Rabbits

The purpose of the study was to determine whether or not physical stimulation by tubal insemination had any unfavourable influences upon the tubal fimbria. Tubal insemination was carried out on 14 rabbits and subsequent pregnancy results were monitored. After a period of 69 − 123 days following tubal insemination, 10 of the rabbits were mated spontaneously and these rabbits were then monitored for pregnancy. Newborn were obtained, with normal gestation periods in six out of the 14 rabbits, following tubal insemination and all 10 of the rabbits that were mated spontaneously with males following tubal insemination subsequently delivered. It is concluded that physical stimulation by tubal insemination does not produce adhesive changes on the tubal fimbria.

Magnetic resonance imaging features and clinical signs associated with presumptive and confirmed progressive myelomalacia in dogs: 12 cases (1997-2008).

OBJECTIVE To characterize clinical signs and findings from magnetic resonance imaging (MRI) and CSF analysis for dogs with progressive myelomalacia (PM) diagnosed on the basis of clinical and histologic features. DESIGN Retrospective case series. ANIMALS 5 dogs with confirmed PM and 7 with presumptive PM evaluated from 1997 through 2008. PROCEDURES Medical records of study dogs were reviewed, and clinical signs and MRI and CSF findings were evaluated. A clinical diagnosis of PM was made on the basis of detection of disk-associated spinal cord compression via MRI and progression of clinical signs from initial paraparesis or paraplegia to thoracic limb lower motor neuron paresis to tetraplegia associated with cranial migration of the extent of cutaneous trunci reflex extinction and analgesia, terminating in death due to respiratory paralysis. RESULTS All dogs were paraplegic and had signs of lower motor neuron lesions. As revealed by MRI of the vertebral column, the length of abnormal signal intensity was more than 6-fold, compared with the body length of L2. In some dogs, these abnormal MRI findings were observed before PM was clinically diagnosed. The CSF examination revealed hemorrhagic xanthochromia. CONCLUSIONS AND CLINICAL RELEVANCE A hyperintense region of the spinal cord > 6 times the length of L2 on T2-weighted imaging might be a characteristic MRI finding of PM. In some dogs, such MRI findings were observed before PM was clinically diagnosed. Progressive myelomalacia may thus be diagnosable at the early stage through MRI and CSF examination before signs of PM develop.

Clinical improvement in two dogs with hydrocephalus and syringohydromyelia after ventriculoperitoneal shunting

Two young Miniature Dachshunds were presented with abnormal gait. Magnetic resonance imaging showed, hydrocephalus with expanding fourth ventricle, and syringohydromyelia in the cervical spinal cord. These dogs underwent ventricle-peritoneal shunting, after which hydrocephalus, syringohydromyelia, and their clinical signs, improved.

Diagnosis of olfactory neuroblastoma in a dog by magnetic resonance imaging

FIG 1: Olfactory neuroblastoma in a dog, showing isointensity on (a) a T1-weighted (TR 350 TE 15 FA 90 NEX 2·5) dorsal image (arrow), and (b) a T2-weighted (TR 4000 TE 120 FA 90 NEX 2·5) dorsal image (arrow). (c) The tumour is enhanced by the contrast medium gadoteridol (arrow). (d) The cyst compressing the frontal lobe can be seen caudal to the tumour; on the contrast T1-weighted parasaggital image, the tumour can be seen extending into the intracranial cavity (a) (b)

Subdural accumulation of fluid in a dog after the insertion of a ventriculoperitoneal shunt

A dog with hydrocephalus as a result of aqueduct stenosis and cerebellar herniation underwent ventriculoperitoneal shunting. Magnetic resonance images and computed tomography scans taken after the surgery revealed subdural accumulations of haemorrhagic fluid and cereberocortical collapse caused by overshunting and leakage of cerebrospinal fluid from the site of insertion of the shunt. However, the degree of cerebellar herniation was reduced after the shunt was inserted, and the dog did not develop any neurological signs and made good progress.

Fimbrial Capture of the Ovum and Tubal Transport of the Ovum in the Rabbit, with Emphasis on the Effects of β2-Adrenoreceptor Stimulant and Prostaglandin F2α on the Intraluminal Pressures of the Tubal Ampullae

Purpose:Our purpose was to elucidate the roles of the ampullar and isthmic portions of the oviduct and the effects of drugs on oviductal contractility.Methods:Prostaglandin F2α (PGF2α; Ono Pharmaceuticals, Osaka) and oxytocin (Atonin-O; Teikoku Hormone Manufacturing Co. Ltd., Tokyo) were used to stimulate oviductal contractility, and ritodrine hydrochloride (Utemerin; Solvay-Duphar Corp., Denmark) to inhibit the contractility.Results:Both PGF2α and Atonin-O were involved in ovum capture by the ampullar oviduct by stimulating contractility, thus altering the intraductal pressures. Utemerin is effective in inhibiting the enhanced contractility induced by PGF2α and Atonin-O.Conclusions:Variations in pressure of the ampullar portion of the oviduct seem necessary for the capture of ova expelled from the ovary. Once in the isthmic portion of the oviduct, transport appears to be under the influence of ciliary activity rather than variations in contractility.

Regeneration of intervertebral disc by the intradiscal application of cross-linked hyaluronate hydrogel and cross-linked chondroitin sulfate hydrogel in a rabbit model of intervertebral disc injury

The degeneration of intervertebral disc (IVD) is a major cause of low back pain. However, there is no satisfactory preventive treatment for degenerative disc disease (DDD). In this study, we examined the effects of a novel cross-linked hyaluronate hydrogel and cross-linked chondroitin sulfate (CS) hydrogel on a rabbit model of IVD injury. We injected 300 microl of phosphate buffer saline, 1% sodium hyaluronate, cross-linked hyaluronate hydrogel, or cross-linked CS hydrogel into the injured IVDs. One, three or six months after treatment, the whole spinal columns were dissected and magnetic resonance (MR) images of the IVDs were examined. It was noted that the IVD, which was injected with cross-linked hyaluronate hydrogel or cross-linked CS hydrogel mostly retained the normal signal intensity of the MR images. These IVDs exhibited a higher degree of staining with safranin-O than the control discs or 1% sodium hyaluronate-injected discs, suggesting that the intradiscal application of cross-linked hyaluronate hydrogel or cross-linked CS hydrogel probably inhibits the degenerative cascade of the DDD. The intradiscal administration of these drugs is safe, easy and costs less. In the near future, these intradiscal injections may become the standard therapy for the treatment of DDD instead of the spine surgeries.

The Yield of Abnormal Unfertilized Eggs Observed after Repeated Gonadotrophin-Induced Ovulation

This study investigated whether or not the yield of abnormal eggs produced after repeatedly induced ovulation could be reduced by increasing the interval between gonadotrophin (GTH) administrations. Ovulation was induced, in a mouse model, by subcutaneous injection of pregnant mare serum GTH and human chorionic GTH given once (n = 10), twice (n = 10), three times (n = 10) or four times (n = 10) at intervals of 5 days. In 30 further mice, a fifth induction was performed either 5 (n = 10), 10 (n = 10) or 20 days (n = 10) following the fourth injection. Oviducts were examined microscopically, and the eggs were counted and examined for morphological abnormalities. In the mice who had received four GTH treatments, 33.3% (12 of 36) of the eggs were abnormal. After the fifth induced ovulation performed after an interval of 5, 10 or 20 days, the yield of abnormal eggs was 50.0% (five of 10), 23.1% (nine of 39) and 15.2% (seven of 46), respectively. These results indicate that prolongation of the interval between GTH administrations reduced the yield of abnormal eggs produced following repeatedly induced ovulation.

Investigation of Ovum Transport in the Oviduct: The Dynamics of Oviductal Fluids in Domestic Rabbits

Ova are captured by the oviductal fimbria and rapidly transported to the ampullary-isthmic junction of the fallopian tube. Fertilized ova and oviductal fluids are then carried medially in the fallopian tube, while undergoing maturation in preparation for entering the uterine cavity, where nidation and further development take place. This movement of oviductal fluids was visualized in a rabbit model with human chorionic gonadotropin-induced ovulation, by injection of a contrast medium into the ampulla region of the oviduct. In the ampulla, the opaque medium was observed to oscillate at 0 − 85.4 mm/s. This medial transport of the fluid towards the uterus decreased to 0 − 9.6 mm/s in the isthmic portion of the tube. This decrease substantiates previous findings that the transport of material in the isthmic portion of the oviduct is more strongly under the control of ciliary action than under peristaltic activity.