Objectives: Severe intervertebral disc herniation causes complete paraplegia and loss of pain sensation in canines. The prognosis is poor, even when decompression surgery is performed immediately after onset. Studies suggest that bone marrow-derived mononuclear cells will regenerate the injured spinal cord and restore neurologic function. This study was conducted to assess the clinical efficacy of bone marrow-derived mononuclear cell autotransplanting in severe cases of canine intervertebral disc herniation. Materials and Methods: Eighty-two dogs (miniature dachshunds) with severe thoracolumbar intervertebral disc herniation were used. All had intervertebral disc herniation accompanied by paraplegia and loss of pain perception. In 36 dogs, bone marrow-derived mononuclear cells were autotransplanted to the lesioned spinal cord immediately after decompression surgery. Bone marrow was collected from the proximal humerus and subjected to density gradient centrifugation to isolate the bone marrow-derived mononuclear cells. The remaining 46 dogs (receiving surgical treatment only) were assigned as controls.Therapeutic efficacy was compared based on the rate of ambulatory recovery. Results: Ambulatory recovery was observed in 88.9% and 56.5% of animals in the bone marrowderived mononuclear cells and control groups, and a significant difference was found. No complications were found in bone marrow-derived mononuclear cells group. Conclusions: Bone marrow-derived mononuclear cell transplanting revealed a significant increase in the recovery rate and, as has been reported in rats and humans, bone marrow-derived mononuclear cell autotransplanting shows efficacy in canines as well.

Feline leukemia virus (FeLV) clone33 was obtained from a domestic cat with acute myeloid leukemia (AML). The long terminal repeat (LTR) of this virus, like the LTRs present in FeLV from other cats with AML, differs from the LTRs of other known FeLV in that it has 3 tandem direct 47-bp repeats in the upstream region of the enhancer (URE). Here, we injected cats with FeLV clone33 and found 41% developed myelodysplastic syndromes (MDS) characterized by peripheral blood cytopenias and dysplastic changes in the bone marrow. Some of the cats with MDS eventually developed AML. The bone marrow of the majority of cats with FeLV clone33 induced MDS produced fewer erythroid and myeloid colonies upon being cultured with erythropoietin or granulocyte-macrophage colony-stimulating factor (GM-SCF) than bone marrow from normal control cats. Furthermore, the bone marrow of some of the cats expressed high-levels of the apoptosisrelated genes TNF-a and survivin. Analysis of the proviral sequences obtained from 13 cats with naturally occurring MDS reveal they also bear the characteristic URE repeats seen in the LTR of FeLV clone33 and other proviruses from cats with AML. Deletions and mutations within the enhancer elements are frequently observed in naturally occurring MDS as well as AML. These results suggest that FeLV variants that bear URE repeats in their LTR strongly associate with the induction of both MDS and AML in cats.

In this report we describe changes in the intracellular redistribution of raf serine/threonine protein kinase (product of the raf proto-oncogene family) in hippocampal neurons following cerebral ischemia in Mongolian gerbils. For immunohistochemical localization studies polyclonal antisera specific for each of the A, B, and Raf-1 isotypes of raf, as well as a pan-raf antisera, were employed. Of these, only sera recognizing B-raf, as well as the general v-raf (raised against the conserved C-terminal region) were positive, indicating that B-raf is the major isotype in this neuronal region. Three different ischemic models were used (repeated 3 times for two min and single 5 or 15 min occlusions, of the common carotid arteries) to demonstrate that ischemic insult causes redistribution of raf protein kinase into the cell nucleus of hippocampal neurons. Increased amounts of raf protein in the nuclei of pyramidal cells following ischemia was confirmed by Western blot analysis of isolated nuclear fractionations. Moreover, an elevation in the level of nuclear raf protein also was detected in the contralateral (i.e. non-occluded hemisphere) neurons of CA1 and CA3 subfields 4 days after the ischemic insult indicating a possible transsynaptic increase in the amount of raf protein along with redistribution. The intranuclear translocation of the immunoreactive material started from the perinucleolar rim and with time extended throughout the nucleus. Enhanced levels and altered redistribution of the raf polypeptide in the nuclei of pyramidal cells of the CA3 subfield appears to be reversible and returns to the normal level 12 days following the ischemic insult.(ABSTRACT TRUNCATED AT 250 WORDS)

ABSTRACT. An eleven-year-old female pug was referred to Yamaguchi University Animal Hospital for evaluation of anemia and thrombocytopenia. The cytological examination of the peripheral blood showed some giant monocytic lineage blast cells. A few granulocytes and platelets had dysplastic features. On day 7, in addition to increasing the monocytic lineage cells, the dysplastic features of the blood had also increased compared to the initial examination. We performed bone marrow aspiration upon her death. The bone marrow revealed dysplastic features in all three hematopoietic cell lines, and an increase in the monocytic cell line. Based on the features of the bone marrow and the peripheral blood, this case was confirmed to be myelodysplastic syndrome-Chronic myelomonocytic leukaemia (MDS-CMML).

Cysteinyldopas and Dopa in the urine and tissues of Japanese melanoma patients were investigated quantitatively by means of high-performance liquid chromatography. Cysteinyldopa isomers were detected in the urine of eumelanic Japanese patients. The amount (X +/- SD%) of each isomer of cysteinyldopa in the urine was 80.26 +/- 4.66% in 5-S-cysteinyldopa, 9.39 +/- 1.64% in 2-S-cysteinyldopa, 7.07 +/- 3.33% in 2, 5-S, S-dicysteinyldopa, and 3.28 +/- 1.43% in 6-S-cysteinyldopa. The amount of cysteinyldopa in melanoma tissues was 26-314 times more than that of Dopa. The amount (X +/- SD%) of cysteinyldopa in the tissues was 80.34 +/- 1.75% in 5-S-cysteinyldopa, 11.06 +/- 1.91% in 2-S-cysteinyldopa, 6.27 +/- 1.43% in 2, 5-S, S-dicysteinyldopa, and 2.34 +/- 0.61% in 6-S-cysteinyldopa. The fact that the percentages of each isomer of cysteinyldopa in the urine and in the tissues were approximately constant suggests that the cysteinyldopas secreted from melanoma cells were excreted into the urine without being metabolized.

Feline myelodysplastic syndromes (MDS) has been diagnosed in many cats infected with feline leukemia virus, although the pathogenesis of this hematopoietic deficiency has been unclear. In this study, we assayed the bone marrow erythroid colony-forming units (CFU-E) and granulocyte-machrophage CFUs (CFU-GM) to investigate the pathogenesis of feline MDS. The number of CFU-E colonies was decreased in 4 of 7 cats with MDS, and the number of CFU-GM colonies was also decreased in 4 cats. Furthermore, small colonies of CFU-GM were found in all 7 cases. These findings indicated that refractory cytopenia of feline MDS could be caused by abnormal maturation and differentiation of hematopoietic stem cells in bone marrow, as it is in human MDS. The pathogenesis of feline MDS might be similar to that of human MDS.

ABSTRACT. A three-year-old dog with marked leukocytosis, lymphadenopathy, and diarrhea showed an increase in unidentified blasts in the peripheral blood, and they were proliferated in the bone marrow. The dog was diagnosed with myelomonocytic leukemia (M4) because the blast cells were demonstrated by cytochemical staining to be both myeloid and monocytic cells. Although the dog was treated with a multi-combination chemotherapy and induction therapy using vitamin K 2 , it died on day 47 after the first admission. This case is the first report of M4 in Japan.

A three-year-old cat with lymphadenopathy, non-regenerative anaemia and marked leucocytosis (171.3 x 10(9) white blood cells/l) was diagnosed with monocytic leukaemia and treated with a combination of anticancer drugs. A number of mature and immature monocyte-like cells were detected in the peripheral blood and bone marrow; they proved to be monocytic cells by cytochemical examination and an analysis of their cell surface phenotype, indicating that the cat suffered from acute myeloid leukaemia, subclassified as monocytic leukaemia (M5). Treatment with cytarabine, doxorubicin, vincristine and prednisolone greatly reduced the number of blast cells in the cat's peripheral blood and bone marrow. The cat was in partial remission for 67 days and survived for 95 days after it was first examined.