Role of aggrecanase and MMP in cartilage degradation

Aritcular cartilage damage results in degradation of macromolecular in cartilage tissue such as aggrecan and type II collagen that are mediated with aggrecanases and matrix metalloproteinases. As the activity of MMP-13 against Type II collagen is very strong, so it plays significant role in cartilage collagen degradation. However, it is noteworthy that the inhibition of both aggrecanse-1. 2 can prevent cartilage degradation. Aggrecan hydrates the collagen network and provides the cartilage tissue with its characteristic pressibility and elasticity. It become now clear that aggrecan plays protective role in preventing degradation of collagen fibrils. Aggrecan and type II collagen molecules cooperatively maintain the cartilage integrity and function.     

Serum cortisol as a predictive marker of the outcome in patients resuscitated after cardiopulmonary arrest

OBJECTS: To analyze the relationship between stress hormones (arginine vasopressin (ADH), adrenocorticotropic hormone (ACTH) and cortisol and the outcome of patients resuscitated after cardiopulmonary arrest (CPA). METHODS: Thirty-six patients were enrolled in this study. In 36 of the resuscitated cases, 27 were non-survivors and 9 survived. The survival group was defined as cases either in a persistent vegetative state, with some disability or good recovery 1 month after return of spontaneous circulation (ROSC). The non-survival group was defined as cases who died within 1 month. RESULTS: The plasma ADH and ACTH levels and the serum cortisol levels in both the surviving and the non-surviving patients were 82.3+/-74.5 and 149.6+/-135.4 (pg/ml), 239.7+/-327.4 and 282.4+/-553.0 (pg/ml), 34.1+/-11.2 and 19.0+/-12.8 (g/ml) (mean+/-S.D., respectively). The plasma ADH and ACTH levels showed no significant difference between the two groups. The serum cortisol levels were significantly higher in survivors than in the non-survivors (P=0.029). We also used the receiving-operating characteristics (ROC) curves to evaluate the optimal cutoff value of the concentration of serum cortisol as a predictive maker of non-surviving patients. The cutoff value of 16.7 g/ml for the concentrations of serum cortisol was a 1.00 positive predictive value and a 1.00 specificity at a 0.519 negative predictive and a 0.409 sensitivity for predicting non-surviving patients. The area under the ROC curve was calculated to be 0.858 at a prevalence of 0.58. The plasma ADH levels correlated significantly and positively with the plasma ACTH levels (r=0.516, P<0.0010). CONCLUSIONS: We concluded that the serum cortisol levels were significantly higher in survivors than in non-survivors resuscitated after CPA.     

Association between serum C-reactive protein elevation and left ventricular thrombus formation after first anterior myocardial infarction

STUDY OBJECTIVES: Most left ventricular (LV) thrombi that occur after acute myocardial infarction (AMI) are formed within 2 weeks, when inflammatory cells have infiltrated into the necrotic myocardium. Inflammatory changes on the endocardial surface may induce platelet deposition and fibrin net formation through interaction with proinflammatory cytokines. We sought to determine the significance of the inflammatory response reflected by serum C-reactive protein (CRP) elevation in LV thrombus formation after AMI. DESIGN: We examined 160 patients with first anterior AMI. Peak serum creatine kinase (CK) and CRP levels were determined by serial measurements. Echocardiography was performed 10 to 14 days after the onset. We assessed the association between the elevation of serum CRP levels and LV thrombus formation after AMI. RESULTS: LV thrombus was observed in 13 patients (8%). There was no difference in age, sex, coronary risk factors, preinfarction angina, use of revascularization therapy and anticoagulant therapy, platelet count, and fibrinogen level on hospital admission between the two groups. The mean (+/- SD) peak serum CRP level was markedly increased in patients with LV thrombus compared to those without (18.0 +/- 12.6 vs 9.4 +/- 8.1 mg/dL; p = 0.001), despite their having similar peak CK levels. Multivariate analysis showed that a peak CRP level of > or =20 mg/dL was an independent predictor of thrombus formation (relative risk, 4.82; p = 0.037) among variables including older age (> or =60 years old), peak CK level (> or =3,000 IU/L), and peak WBC count (> or =12,000 cells/ microL). CONCLUSION: A greater elevation of serum CRP level was associated with a higher incidence of LV thrombus after AMI, suggesting an important role of the inflammatory response in mural thrombus formation.     

Five cases of locally advanced rectal cancer or local recurrence performed intra-arterial infusion chemotherapy via the internal iliac artery

Intra-arterial infusion chemotherapy via the internal iliac artery was performed in 5 patients with locally advanced rectal cancer or recurrent rectal cancer. Arterial infusion chemotherapy was conducted into the internal iliac artery via bilateral femoral artery following a blood flow change with a coil. 5 FU 500 mg and l-leucovorin 125 mg/m2 were injected weekly. An average time of injections or its duration was 40 (17-74) times or 12.8 (5-23) months, respectively. Disappearance or improvement of symptoms was observed in 4 cases. A decrease of tumor size observed by CT was in 2 cases and a decrease of blood CEA level was in 3 cases. As for the complication of arterial infusion chemotherapy, dermatopathy was found in all of the cases, and sensory disturbance of lower extremities was in 3 cases, infection was in 2 cases and catheter obstruction was in 2 cases. A decrease of dosage or abundance of continuation was done during the course due to complications. Two patients with primary cancer died 1-3 years after the treatment, and 2 patients with recurrence died 7 months to 1 year after the treatment. One patient with primary cancer is continuing the treatment for the last 2 years though multiple metastatic diseases have been confirmed.     

Mucosa-associated lymphoid tissue lymphoma presented as diffuse swelling of the parotid gland

Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct subtype of lymphoma. Parotid MALT lymphoma is a rare tumor that is hard to diagnose by fine-needle aspiration cytology. Therefore, partial parotidectomy is often required for a pathological diagnosis. We report a case of MALT lymphoma presented as unilateral diffuse swelling of the parotid gland, who was diagnosed by partial parotidectomy and underwent radiotherapy.     

Forty-three cases of obturator hernia

BACKGROUND: Obturator hernia is a relatively rare pelvic hernia and usually occurs in elderly, thin, multiparous women. Because symptoms are nonspecific, the diagnosis is often delayed until laparotomy is performed form to treat bowel obstruction. METHODS: Forty-three patients with obturator hernia undergoing surgery at Tokyo Metropolitan Geriatric Hospital were divided retrospectively into two groups (group A = 23 patients from 1968 to 1986 before computed axial tomography [CAT] was developed; group B = 20 patients from 1987 to 1999 after CAT). Preoperative diagnosis, operative procedures, and postoperative course were reviewed and compared between the 2 groups. RESULTS: Preoperative diagnostic accuracy was significantly higher in group B at 80.0% (16 of 20 patients) than in group A at 43.5% (10 of 23 patients) (P = 0.0146). Rate of gut resection and mortality were significantly lower in group B at 25.0% (4 of 20) and 5.0% (1 of 20) than in group A at 52.2% (12 and 23) and 30.4% (7 of 23) (P = 0.0295 and P = 0.0385, respectively). CONCLUSIONS: The use of pelvic CAT in cases of suspected obturator hernia significantly enhances preoperative diagnostic accuracy and helps to decrease both intestinal resection rate and surgical mortality.     

Altered adhesion efficiency and fibronectin content in fibroblasts from schizophrenic patients

Cultured fibroblasts from the cutaneous tissue of 16 schizophrenic patients were compared with 16 control cultured fibroblasts from the healthy subjects. The fibroblasts from the schizophrenic patients showed a decreased adhesion efficiency within 30 min after plating compared to that of the control subjects. However, after 90 min, there was no significant difference between the groups, where more than 90% of the cells from both groups had adhesed to the plate. By immunohistochemistry and western blotting using the antibodies against integrin (VLA5), talin, vinculin, fodrin, vimentin, ankyrin, plectin, fibronectin, and focal adhesion kinase (FAK), there was no significant difference in localization and amount between the groups. The amount of fibronectin released into the medium in which the fibroblast had already kept confluency showed no significant difference between the groups. However, the fibronectin content in cell lysate within 48 h after plating was significantly lower in the schizophrenic group.     

Effects of intracerebroventricular administration of ethylcholine aziridinium ion on hippocampal cholinergic system,assayed in vivo by a brain dialysis technique,and on spatial memory of rats

We attempted to clarify the effect of hippocampal function on the spatial memory of rats by creating a lesion in the hippocampus with ethylcholine aziridinium ion (AF64A). The hippocampus was damaged by injecting AF64A into the lateral ventricles, 3 nmol/3 μl per side. At 1 or 4 weeks after the injection, acetylcholine (ACh) was measured in perfusion samples collected via brain dialysis of the hippocampus of freely moving rats. The release of ACh stimulated by scopolamine was reduced at 1 week but not at 4 weeks post-injection. A behavioral change on the eight-arm radial maze test was also observed in the acquisition or retention trials to determine the deficit in spatial memory, whether acquisition or retention. In the acquisition trial, the initial correct response was decreased and the total error count was increased at 1.5 to 2.5 weeks, but not at 3 weeks, after the AF64A injection. However, those indices remained unchanged in the retention trial. These observations suggest that the hippocampus may be required for the acquisition of spatial memory, but that the stored memory, but the stored memory is located outside the hippocampus, the hippocampus is not concerned with the retrieval process, or the retrieval process may be hippocampal but not cholinergic. The hippocampal cholinergic system would be concerned with the acquisition of spatial memory. Thus, AF64A-treated rats may serve a model for hippocampal cholinergic dysfunction and the recovery from hippocampal cholinergic damage. © 1993 Wiley-Liss, Inc.     

Effect of induced-hypothermia on short-term survival after volume-controlled hemorrhage in pigs

OBJECTIVE: To examine whether induced hypothermia could prolong short-term survival after volume-controlled hemorrhagic shock (HS). MATERIALS AND METHODS: Fifteen pigs with systemic heparin underwent blood withdrawal of 30 ml/kg over 15 min under spontaneous breathing with halothane anesthesia. The pigs were divided into three groups of five pigs each: Group 1, hemorrhage plus hypothermia with extracorporeal shunt circulation (ECSC); Group 2, hemorrhage plus normothermia with ECSC; and Group 3, hemorrhage alone. For Groups 1 and 2, arteriovenous ECSC was performed for 20 min during HS. The re-infused shunt blood was cooled down to approximately 15 degrees C in Group 1, whereas it was returned at 37.5 degrees C in Group 2. The pigs in Group 3 had no ECSC and were left at room temperature. All pigs were observed until their death or for a maximum of 240 min. RESULTS: The mean pulmonary artery temperature (T(pa)) of Group 1 animals decreased to 34.5 degrees C at 15 min after the initiation of ECSC, and thereafter remained at 35.5 degrees C after undergoing ECSC. The T(pa) values for Groups 2 and 3 animals remained at 37.5 degrees C throughout the experiment. All five pigs in Group 1 survived until 240 min, whereas all pigs in Group 2 and 3 of five pigs in Group 3 died before 215 min after blood withdrawal. A life table analysis revealed significantly increased survival in Group 1 compared with Group 2 (P<0.01) and Group 3 (P<0.05). CONCLUSIONS: In lightly anesthetized pigs during volume-controlled HS, induced hypothermia may prolong their short-term survival for reasons that remain to be clarified.     

Revascularization and function of pancreatic islet isografts in diabetic rats following transplantation

In pancreatic islet transplantation, revascularization is crucial for the graft's survival and function. In this study, the endothelium of isolated islets and revascularization and function of islet isografts in diabetic rat were investigated. Islets were isolated from Lewis rats by collagenase digestion method and were examined using immunohistochemistry (CD31 stain) on days 0, 1, 3, and 7 after isolation. The number of CD31-positive cells in these isolated islets was counted (mean +/- SD %). Isografts (freshly isolated islets: group A, and islets cultured for 7 days: group B) transplanted in the renal subcapsule of streptozotocin-induced diabetic Lewis rats were examined using immunohistochemistry (CD31 stain) on days 3, 5, and 7 after transplantation. Intravenous glucose tolerance tests (IVGTT) were performed on days 3 and 7 after transplantation. The number of CD31-positive cells in the isolated islets on days 0, 1, 3, and 7 after isolation were: 17.3 +/- 4.1%, 8.2 +/- 0.7%, 2.1 +/- 0.8%, and 0.8 +/- 0.5%, respectively (p < 0.05). On day 5 after transplantation, CD31-positive cells were not detected in group A and B grafts, but were detected in both groups in periphery of the islets. On day 7, CD31-positive microvessels were present throughout the entire graft. IVGTT values in groups A and B on days 3 and 7 after transplantation did not show significant differences. In renal subcapsular isografts in diabetic rats, revascularization into islet grafts occurs from the surrounding host tissue 5 days after transplantation, but has no influence on the response to glucose during this period.