Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor).

CTGF/CCN2, a hypertrophic chondrocyte-specific gene product, possessed the ability to repair damaged articular cartilage in two animal models, which were experimental osteoarthritis and full-thickness defects of articular cartilage. These findings suggest that CTGF/CCN2 may be useful in regeneration of articular cartilage. INTRODUCTION: Connective tissue growth factor (CTGF)/CCN2 is a unique growth factor that stimulates the proliferation and differentiation, but not hypertrophy, of articular chondrocytes in vitro. The objective of this study was to investigate the therapeutic use of CTGF/CCN2. MATERIALS AND METHODS: The effects of recombinant CTGF/CCN2 (rCTGF/CCN2) on repair of damaged cartilage were evaluated by using both the monoiodoacetic acid (MIA)-induced experimental rat osteoarthritis (OA) model and full-thickness defects of rat articular cartilage in vivo. RESULTS: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2. Therefore, CTGF/CCN2 was suspected to play critical roles in cartilage repair. In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage. Next, to examine the effect of rCTGF/CCN2 on the repair of articular cartilage, we created defects (2 mm in diameter) on the surface of articular cartilage in situ and implanted rCTGF/CCN2-hydrogel or PBS-hydrogel therein with collagen sponge. In the group implanted with rCTGF/CCN2-hydrogel collagen, new cartilage filled the defect 4 weeks postoperatively. In contrast, only soft tissue repair occurred when the PBS-hydrogel collagen was implanted. Consistent with these in vivo effects, rCTGF/CCN2 enhanced type II collagen and aggrecan mRNA expression in mouse bone marrow-derived stromal cells and induced chondrogenesis in vitro. CONCLUSION: These findings suggest the utility of CTGF/CCN2 in the regeneration of articular cartilage.     

NEW METHOD OF STENTING TREATMENT FOR MALIGNANT DUODENAL STENOSIS: USING DOUBLE‐BALLOON ENTEROSCOPY

Recently, a self‐expandable metallic stent has been recognized for treatment of malignant duodenal stenosis. But the complications by stenting are important problems even now. In the present study, we report our new method of duodenal stenting by using of double‐balloon enteroscopy considered safe and effective.     

Small extra-adrenal pheochromocytoma causing severe hypertension in an elderly patient.

We report the case of a 67-year-old woman with severe hypertension caused by an extra-adrenal pheochromocytoma. The tumor was detected by 131I metaiodobenzylguanidine scintigraphy and it was found to be small (2 cm ?) by enhanced CT. After the extirpation of the tumor, the blood pressure of the patient immediately normalized. It should be taken into account that a small extra-adrenal pheochromocytoma can be one of the causes of secondary hypertension in elderly patients. Since small extra-adrenal pheochromocytomas are difficult to detect, it is also important to perform suitable examinations to establish the diagnosis. Furthermore, we emphasize the importance of an accurate diagnosis in elderly patients with pheochromocytoma, for they often have less symptomatology and more severe cardiovascular complications due to refractory hypertension than younger patients.     

Topographical Displays of Somatosensory Evoked Potentials

Abstract: The distribution of somatosensory evoked potentials (SEPs) after stimulation of the median nerve at the wrist was examined in 10 normal subjects using isopotential maps. The latencies of continuous negative and positive peaks were measured in each lead. The differences of the potentials at these latencies were measured in all the leads and the isopotential maps were constructed. The distribution of P0–NI was all similar. The latencies of P0 were almost the same in all the leads at about 13 msec. The distribution of NI-PI-NII was divided into three types—N16–P20–N28 localized in the frontal region, N17–P22–N30 localized in the central region and N19–P25–N33 distributed in the parieto-occipito-temporal regions. The distributions of NII-PII and PII-NIII were all similar, with high amplitudes in the central region. The latencies of PII and NIII were almost the same in all the leads at about 45 msec and 68 msec.     

Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.     

Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts.

OBJECTIVE: NKH477 was recently identified as a water-soluble forskolin derivative and was reported to prolong survival of murine cardiac allografts. However, the mechanism of the efficacy is not clear in vivo. The aim of this study was to investigate the immunosuppressive effects of NKH477 on acute lung allograft rejection in the rat model and its mechanism of action in vivo. METHODS: Left lungs were transplanted orthotopically from Brown-Norway donors to Lewis recipients. Recipient rats were untreated or treated daily with different doses of NKH477. Grafts were excised on Day 3 or Day 5 to determine histopathological rejection and expressions of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma by enzyme-linked immunosorbent assay. The cytokine expression at Day 3 or Day 5 was also evaluated in recipient spleens by immunohistochemistry. Furthermore, mesenteric lymph node cells from recipients at Day 5 were cultured alone or stimulated with donor antigens for 72 hours to determine cell proliferation by means of thymidine incorporation. RESULTS: NKH477 significantly extended allograft survival time in a dose-dependent manner and reduced histopathological rejection. Treatment with NKH477 inhibited IFN-gamma and IL-10 expression, whereas expression of these cytokines were markedly upregulated in the untreated allografts. Expression of IL-2 and IL-10 also increased in the spleen of untreated allorecipients. NKH477 suppressed expression of both cytokines in the spleen. In addition, lymphocyte proliferation was inhibited in NKH477-treated recipients as compared with untreated recipients. CONCLUSION: These results suggest that NKH477 exerts an antiproliferative effect on lymphocytes in vivo with an altered cytokine profile in rat recipients of lung allografts.     

Surgical treatment of pseudoaneurysm of the sinus of valsalva after aortic valve replacement for active infective endocarditis.

Pseudoaneurysm is an uncommon and serious complication of infective endocarditis (IE). It is often fatal because of its rapid progress, high rates of rupture and recurrence, and worsening effects on the systemic condition. We report the rare case of a patient who developed a pseudoaneurysm of the sinus of Valsalva two months after emergency aortic valve replacement for active IE. At the previous operation, we had directly closed a small fistulous hole in the non-coronary sinus of Valsalva using two mattress sutures with autologous pericardial pledgets, because the tissue surrounding the hole did not appear to be infected on visual inspection. A pseudoaneurysm developed from this portion due to detachment of sutures. If the fistula had been completely resected during the first surgery instead of performing a simple closure, the pseudoaneurysm of the sinus of Valsalva would not have formed. However, the primary aim of the first emergency surgery was to spare the life of a critically ill patient. In the second surgery, the pseudoaneurysm was completely resected with the aortic wall--including the non-coronary sinus of Valsalva and the communicating hole. Then, patch plasty of the non-Valsalva sinus was successfully performed.     

A case of malignant fibrous histiocytoma with metastatic brain tumors after tumorgenic embolism]

A 61-year-old man had been treated for malignant fibrous histiocytoma with the pulmonary and the lymph node metastasis in the department of orthopedics in our hospital. He was admitted to our department because of an acute onset of conscious disturbance and non-fluent aphasia. Diffusion-weighted imaging (DWI) showed high signal intensity areas in the bilateral cerebella, thalami and posterior lobes. T2WI did not show any mass effects. Enhanced CT did not reveal any enhanced lesion. He was diagnosed as having cerebral embolism, and his conscious disturbance was improved after medication. Eight weeks later, he presented dysphagia, dysarthria, and ataxia in his extremities. DWI showed multiple lesions of low signal intensity located at the identical place where had showed high signal intensity in the initial DWI. T2WI showed high signal intensity area with mass effect. It was indicated that cerebral metastasis might grow after tumorgenic embolism. This is a rare case that tumor emboluses were developed to the metastatic brain tumors.     

A case of acute disseminated encephalomyelitis (ADEM) associated with peripheral neuropathy]

A 17-year-old boy with high fever, headache, and neck stiffness was admitted to our hospital. Spinal fluid showed a protein level of 215 mg/dL with myelin basic protein (579 pg/mL), 347/ microl cells (330 mononuclear cells), and a glucose level of 53 mg/dL. One week later, urinary retention, flaccid paraplegia, and sensory disturbance below the 10th thoracic level developed. MRI of the spinal cord revealed swelling and T2-high intensity area in the cord at the 11th and 12th thoracic level. Although high-dose of methylprednisolone was administered, consciousness disturbance and respiratory failure that required mechanical ventilation occurred. Bilateral abducens nerve palsy, nystagmus, and flaccid tetraparesis also occurred. Brain MRI revealed T2-high intensity area in the midbrain and pons. Nerve conduction study showed diminished amplitudes and prolonged latencies or absence of F waves. The patient was administered a combination of intravenous immunoglobulin and a high-dose of methylprednisolone. He showed improvement within one week after the treatment. Two weeks later, he recovered from respiratory failure and weakness of the upper limbs. He remained paraplegic, but gradually improved and was able to walk with support one and a half years later. We suggest the combination therapy of intravenous immunoglobulin and a high-dose of methylprednisolone is effective for patients with combined ADEM and peripheral neuropathy.