Periodic knee injections of BMP‐7 delay cartilage degeneration induced by excessive running in rats

Strenuous running of rats enhances mechanical stress on the knee, thereby inducing degeneration of articular cartilage. Bone morphogenetic protein‐7 (BMP‐7) has an inhibitory effect on cartilage degeneration, suggesting its usefulness for human osteoarthritis patients. However, its mode of administration should be investigated. We examined whether weekly knee injections of BMP‐7 delayed the progression of cartilage degeneration. Wistar rats were forced to run 30 km in 6 weeks on a rodent treadmill, and BMP‐7 was injected weekly into the knee. Macroscopically and histologically, this strenuous running regimen induced cartilage degeneration. Weekly injections of 250 ng BMP‐7 delayed the progression of cartilage degeneration. Immunohistochemically, in the control knee, type II collagen expression decreased, while BMP‐7 expression in chondrocytes slightly increased. Interestingly, weekly injection of BMP‐7 increased BMP‐7 expression even 9 days after the final injection. Disulfate disaccharide keratan sulfate in serum transiently increased in the control group, while it remained at a low level in the BMP‐7 group. Weekly BMP‐7 injection increased BMP‐7 expression in chondrocytes and its effect seemed to last more than 7 days. The effect of BMP‐7 could be monitored by serum keratan sulfate concentration. Periodical injections of BMP‐7 delayed progression of cartilage degeneration induced by excessive running in rats. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1088–1092, 2009     

Visual hallucinations on eye closure after orthopedic surgery under general anesthesia

A 61-year-old woman suffering from rheumatoid arthritis without a contributory neurological, mental, or psychological history experienced visual hallucinations solely on eye closure after total hip arthroplasty under general anesthesia combined with epidural anesthesia. The visual hallucinations first appeared when she arose from sleep early on postoperative day 1, approximately 12 h after the end of surgery. Only on closing her eyes, she had a clear view of colored clothes, lace curtains, handbags, hats, and sofas, all of which were vivid, realistic, complex, of natural size, and in normal perspective without distortion and appeared independently and randomly in succession. The hallucinations disappeared when she opened her eyes even in the dark. The visual hallucinations gradually decreased as the days elapsed and they had entirely subsided on postoperative day 4. The level and content of her consciousness seemed entirely normal throughout her hospital course. Although postoperative visual hallucinations are not uncommon, they do not always show the closed-eye variation. The causes and underlying mechanisms of this type of visual hallucination remain to be elucidated.     

6‐Formylpterin protects retinal neurons from transient ischemia–reperfusion injury in rats: A morphological and immunohistochemical study

Neuroprotective effects of 6‐formylpterin (6FP) on transient retinal ischemia–reperfusion injury were evaluated in rats by means of counting the number of retinal ganglion cells, measuring the thicknesses of the inner plexiform and inner nuclear layers, and by immunohistochemical detection of apoptotic cells in the retina. Sixty‐one Sprague–Dawley rats (12 weeks, male, 295–330 g) were subjected to transient retinal ischemia–reperfusion by elevated intra‐ocular pressure (80 mmHg for 60 min). Intraperitoneal injection of 6FP (3.8 mg/kg) was performed before or after ischemia. The retina was histologically better preserved in rats with 6FP treatment than without 6FP treatment. 6FP showed more strong neuroprotective effects when it was administered before ischemia. The number of single‐stranded DNA‐positive cells in the retina also decreased remarkably in rats with 6FP treatment, especially when administered before ischemia. These results suggest that 6FP protects retinal neurons from transient ischemia–reperfusion injury, at least in part by inhibiting apoptotic cell death.     

Enhancing effect of thoracotomy and/or laparotomy on the growth of ascitic tumor in rats

To evaluate the effect of operative stress on a tumor growth, thoracotomy and/or laparotomy were performed 48 hours after the intraperitoneal inoculation of Sato lung cancer cells in Donryu rats. The survival time and the spread of the tumor were examined. Thoracotomy and laparothoracotomy reduced significantly the survival time of the inoculated rats as compared with the control but no significant difference was observed between the two test groups subjected to operative stress. No difference was observed in the spread of the tumor between the test groups and the control. These results indicated that the operative stress increased only the number of metastatic foci and did not change the characteristics of the tumor cells. Supported in part by Grants-in-Aid from the Ministry of Education, Science and Culture and the Ministry of Health and Welfare.     

Articular cartilage depicted at optimized angular position of Laue angular analyzer by X-ray dark-field imaging.

Using 36.0 keV X-ray from synchrotron radiation, we examined the optimized angular position of Laue analyzer for depicting articular cartilage of an intact human finger by X-ray dark-field imaging. The surface of articular cartilage was depicted clearly by adopting the offset angle of 0.04 arcsec to lower angular side to the analyzer whilst the contour of articular cartilage was delineated clearly at the other angular positions of the analyzer within the width of the rocking curve.     

A case of cystadenocarcinoma developing from an ovary autografted to the abdominal wall

A 73-year-old woman developed an abdominal tumor. We performed tumor resection. The tumor, located between the fascia and peritoneum, was removed completely. The histological finding was cystadenocarcinoma. Thirty-eight years earlier she had undergone total hysterectomy and bilateral oophorectomy because of abnormal genital bleeding. At that time, her own ovary had been transplanted to the abdominal wall. We diagnosed this tumor as having developed from the autografted ovary. The complication of ovarian autografting is cystic degeneration. This complication is rare in Japan. Moreover, malignant change is extremely unusual in ovarian autografting.     

Selective Suppression of the Generation of Anti-tumor L3T4+ but Not of Lyt-2+ T Cell-mediated Immunity in the Tumor-hearing State

C3H/He mice hyperimmune against syngeneic MH134 hepatoma were prepared by intradermal (id) inoculation of viable tumor cells followed by surgical resection of the tumor and by repeated id challenges with viable tumor cells. Winn assays performed utilizing spleen cells from these mice have revealed that both Lyt-2⁺ and L3T4⁺ T cell subsets from MH134-hyperimmune mice produced complete tumor protection. The in vivo tumor-neutralizing activity was also found in spleen cells from tumor-bearing mice at various times after id implantation of MH134 tumor cells. However, in contrast to comparable tumor-neutralization by Lyt-2⁺ and L3T4⁺ T subsets from hyperimmune mice, only the Lyt-2⁺ T cell subset from tumor-bearing mice was capable of mediating the in vivo protective immunity. L3T4⁺ T cell-mediated immunity was not detectable in the tumor-bearing state irrespective of the length of the sensitization period with a primary growing tumor, but emerged in the mice which resisted the first tumor challenge after the resection of the primary tumor. These results indicate that the emergence of L3T4⁺ T cell-mediated anti-tumor immunity is stage-dependent and the Lyt-2⁺ T cells represent the main functional subset in the tumor-bearing state, although both subsets of T cells are potentially capable of effecting anti-tumor in vivo immunity. The results are discussed in relation to the selective suppression of the L3T4⁺ but not of Lyt-2⁺ T cell function in the tumor-hearing state.     

Oligoclonal Immunoglobulin Gene Rearrangements in Philadelphia Chromosome-positive Common Acute Lymphoblastic Leukemia

The occurrence of more than two rearranged bands of immunoglobulin heavy chain (IgH) genes in B precursor acute lymphoblastic leukemia (ALL) has recently been documented. To elucidate the nature of such leukemias, we studied 30 patients with common ALL, including 6 patients with Philadelphia chromosome (Ph¹)-positive ALL, by immunophenotyping and genotyping. In 10 of the 30, Southern blotting showed oligoclonal patterns of IgH gene arrangements, which were frequently detected in Ph¹-positive ALL. In one patient of the 10, three rearranged bands of Ig k chain genes were detected. Ph¹ abnormality and co-expression of myeloid associated antigens were found in 5 and 5 of the 10, respectively. Detection of multiple fragments of IgH genes would be suggestive of multipotent progenitor origin of these ALL.