Autoantibody against N(epsilon)-(carboxymethyl)lysine: an advanced glycation end product of the Maillard reaction.

Prolonged incubation of proteins with reducing sugar produces advanced glycation end products (AGEs), which are implicated as factors for aging and diabetic complications. We previously demonstrated the presence of N(epsilon)-(carboxymethyl)lysine (CML), one of the main AGE structures, in human and animal tissues using a monoclonal anti-CML antibody (6D12). These findings suggest that CML structures present in vivo could serve as immunogens to generate autoantibodies. This suggestion was tested in the present study. First, plasma samples from diabetic rats reacted positively with AGE bovine serum albumin (BSA). These reactivities increased with the duration of diabetic states and were inhibited specifically by CML-BSA. Second, a fraction purified from plasma of diabetic patients, which bound to AGE-BSA, showed a positive reaction to CML-BSA and furthermore also to human lens proteins, which are known to undergo CML modification in vivo. Finally, patients with renal failure caused by diabetes or nondiabetic pathologies had a higher autoantibody activity against CML structure than that in normal subjects or diabetic patients without renal failure. These results indicate that CML accumulated in vivo serves as an immunological epitope to generate an autoantibody specific for CML that might be used as a potential marker for diabetic nephropathy or chronic renal failure.     

Surgical treatment of thoracic aortic aneurysm in patients with concomitant coronary artery disease

Objective: Surgical treatment of thoracic aortic surgery in patients with coronary artery disease was investigated. Methods: Between 1990 and April 2003, 330 patients underwent elective thoracic aortic surgery. Fifty-six patients who underwent aortic root reconstruction were excluded and 274 patients were examined. Fifty-four (20%) patients showed concomitant coronary artery disease. Ten had undergone coronary revascularization previously; and 3 underwent coronary revascularization [2 coronary artery bypass grafting (CABG), 1 percutaneous transluminal coronary angioplasty (PTCA)] before aortic surgery. Twenty-three patients underwent elective CABG simultaneously and 2 patients had additional coronary artery bypass because of cardiac ischemia during operation. The number of patients who underwent thoracic aortic surgery including Asc Ao+AVR was 2, hemi arch 1, total arch 15, distal arch 5, distal arch+LV aneurysmectomy 1, and thoracoabdominal Ao 1. Two patients underwent coronary revascularization with arterial grafts and the others with SVG grafts. Results: There was one hospital death (4%). In patients without coronary bypass, 2 patients suffered cardiac ischemic events. Conclusion: Our thoracic aortic operations with concomitant CABG using SVG were overall successful. Our current strategies for thoracic aortic surgery in patients with concomitant coronary artery disease include conducting a dipyridamole myocardial perfusion-imaging test first in patients not at risk of coronary artery disease, and if the test is positive, coronary angiography is performed and aggressive coronary revascularization is conducted where possible.     

Irreducible chronic palmar dislocation of the distal radioulnar joint--a case report.

We report a rare case of irreducible chronic palmar dislocation of the distal radioulnar joint (DRUJ). This case showed that the dislocated ulnar head was impacted to the palmar cortex of the radius probably due to the dynamic force of the pronator quadratus muscle. Re-attachment of the ulnar styloid and partial resection of the ulnar head were necessary to make the reduction of the DRUJ possible. The continuity of the radioulnar ligament to the ulnar head was restored and the stability of DRUJ was maintained after reduction.     

Horizontal contralateral approach for the distal anterior cerebral artery aneurysm: technical note

Background

The authors present a modified interhemispheric approach for the distal ACA aneurysm to resolve several problems including the narrow surgical corridor, the difficulty of proximal control, and the aneurysmal projection toward the surgeon.

Methods

We refined the positions of the patient's head and the surgeon. The patient's head is fixed with flexion and tilted to the contralateral side. The surgeon sits on the contralateral side of the patient and not on the cranial side.

Results

The present approach allows the surgeon to comfortably use both hands in the horizontal operative filed, to obtain a minimum retraction of the brain, and to easily secure the proximal artery.

Conclusions

This modified interhemispheric approach is useful for a patient with the distal ACA aneurysm.     

Glucose tolerance and myocardial F-18 fluorodeoxyglucose uptake in normal regions in coronary heart disease patients

To elucidate the relation between glucose tolerance and myocardial uptake of F-18 fluorodeoxyglucose (FDG), FDG-PET with 75 g oral glucose loading was performed on 43 coronary artery disease patients (twice in 2 patients). The patients were divided into 4 groups based on the blood glucose level (BS) and the insulinogenic index (II): group 1, normal (n = 9); group 2, impaired glucose tolerance (IGT, n = 12); group 3, mild diabetes mellitus (DM) (II > 0.4, n = 12); and group 4, severe DM (II < 0.4, n = 12). Percent (%) dose uptake of FDG in the normal regions of the myocardium was not significantly different in groups 1,2, and 3, but it was much lower in group 4 than in groups 1 and 2. In groups 2,3, and 4, % dose uptake showed a definite negative correlation with BS 60 min after glucose loading (r = -0.450, p < 0.05), and a close positive correlation with II (r = 0.363, p < 0.05). These findings indicate that myocardial FDG uptake in normal regions is not greatly impaired in patients with IGT or mild DM. Myocardial viability can be assessed by oral glucose loading in patients with IGT and mild DM as well as in patients with normal glucose tolerance.     

Long-term assessment of hind limb motor function and neuronal injury following spinal cord ischemia in rats

Recent evidence suggests that brain injury caused by ischemia is a dynamic process characterized by ongoing neuronal loss for at least 14 days after ischemia. However, long-term outcome following spinal cord ischemia has not been extensively examined. Therefore, we investigated the changes of hind limb motor function and neuronal injury during a 14-day recovery period after spinal cord ischemia. Male Sprague-Dawley rats received spinal cord ischemia (n = 64) or sham operation (n = 21). Spinal cord ischemia was induced by inflation of a 2F Fogarty catheter placed into the thoracic aorta for 6, 8, or 10 minutes. The rats were killed 2, 7, or 14 days after reperfusion. Hind limb motor function was assessed with the 21-point Basso, Beattie, and Bresnahan (BBB) scale during the recovery period. The number of normal and necrotic neurons was counted in spinal cord sections stained with hematoxylin/eosin. Longer duration of spinal cord ischemia produced severer hind limb motor dysfunction at each time point. However, BBB scores gradually improved during the 14-day recovery period. Neurologic deterioration was not observed between 7 and 14 days after reperfusion. The number of necrotic neurons peaked 2 days after reperfusion and then decreased. A small number of necrotic neurons were still observed 7 and 14 days after reperfusion in some of the animals. These results indicate that, although hind limb motor function may gradually recover, neuronal loss can be ongoing for 14 days after spinal cord ischemia.     

Delayed laparoscopic subtotal cholecystectomy in acute cholecystitis with severe fibrotic adhesions

Background  Conversion rate to open surgery is higher for patients with acute cholecystitis than in those without acute cholecystitis. We attempted to develop a laparoscopic subtotal cholecystectomy to decrease this conversion rate. Methods  From 2000 to 2005, laparoscopic cholecystectomy for acute cholecystitis was performed in 60 patients (22 women, 38 men). Patients were divided into two groups: group A (2000 to 2002, n = 22) and group B (2003 to 2005, n = 38). When significant difficulty was encountered dissecting the gallbladder from its bed, we incised the gallbladder wall leaving the posterior wall and cauterizing the remnant mucosa (subtotal cholecystectomy, SC-1). When dissection of the gall bladder neck and triangle of Calot was difficult, the neck of the gallbladder was sutured despite clipping (SC-2). Results  Mean duration from onset of symptoms to operation was 55.3 ± 52.0 days. SC-1 was performed in 8 patients in group A and 18 patients in group B. SC-2 was performed in three patients in Group B. Conversion rate was 18.1% (4/22) in group A and 0% (0/38) in group B, compared to 0.4% (1/221) for patients without acute cholecystitis. No complications were associated with ablated gallbladder mucosa. Conclusion  Laparoscopic subtotal cholecystectomy offers safe and effective treatment for acute cholecystitis. The conversion rate in group B is decreased by avoiding hazardous dissection of the cystic duct.     

Gene expression profile of renal proximal tubules regulated by proteinuria

BACKGROUND: Proximal tubules activated by reabsorption of protein are thought to play significant roles in the progression of kidney diseases. Thus, identification of genes related to proteinuria should provide insights into the pathological process of tubulointerstitial fibrosis. METHOD: Gene expression profiles were constructed by means of direct sequencing procedures to identify genes induced in the mouse kidney proximal tubules (PT) exposed to proteinuria. RESULTS: By comparing the gene expression of control PT to that of disease model PT, the abundantly expressed genes in control PT were down-regulated presumably because of potentially toxic effects of proteinuria. From the more than 1000 up-regulated genes, an immunity related gene, thymic shared antigen-1 (TSA-1), and a novel gene, GS188, were selected for further characterization. The increased expression of TSA-1, a member of the Ly-6 family, and of GS188 in response to proteinuria was confirmed by Northern analysis, immunohistochemistry, in situ hybridization and laser microdissection along with real-time PCR analysis. Full length cloning of GS188 identified it as a family member of LR8 that was reported to express predominantly in fibroblasts. CONCLUSIONS: The gene expression profiles showed that the expression patterns in PT were changed dramatically by proteinuria. The profiles include novel genes that should be further characterized to aid the understanding of the pathophysiology of progressive kidney diseases.     

A phosphodiesterase inhibitor,pentoxifylline, enhances the bone morphogenetic protein-4 (BMP-4)-dependent differentiation of osteoprogenitor cells

Bone morphogenetic protein-4 (BMP-4), a member of the transforming growth factor-beta superfamily, is capable of initiating differentiation of uncommitted mesenchymal cells into a chondro/osteogenic pathway. This study reports the effects of pentoxifylline (PTX), a nonspecific inhibitor of phosphodiesterases (PDEs), that causes elevation of the intracellular cyclic adenosine monophosphate (cAMP) level on the BMP-4-induced chondro/osteogenic differentiation of a mesenchymal cell line, C3H10T1/2; a bone marrow stromal cell line, ST2; and an osteoblastic cell line, MC3T3-E1. It was found that PTX enhanced BMP-4-induced chondro/osteogenic differentiation in C3H10T1/2 and ST2 cells. Similar effects were observed when adding dibutyryl-cAMP and forskolin. These results indicate that cAMP may potentiate the action of BMP-4 on osteoprogenitor cells, highlighting the possibility that PDE inhibitors could be used as therapeutic agents to enhance bone formation through this effect.     

Neutrophil elastase inhibitor reduces hepatic metastases induced by ischaemia-reperfusion in rats.

OBJECTIVE: To investigate the possibility in rats that ONO-5046 Na, a new recombinant inhibitor of neutrophil elastase, can reduce hepatic metastases induced by ischaemia-reperfusion. DESIGN: Laboratory experimental study. SETTING: Research laboratory, Japan. SUBJECTS: Male Fischer rats. INTERVENTIONS: Rats underwent 60 min of 70% partial hepatic ischaemia, after which rat colon adenocarcinoma cells (RCN-H4) were injected into the spleen. The animals were divided into two test groups and a control group. One group was given ONO-5046 Na intravenously at 10 mg/kg/hour. A second group was given a saline solution for the same period, while the controls were not made ischaemic. MAIN OUTCOME MEASURES: Three weeks after inoculation, the number of tumour nodules on the liver surface was counted. The anti-cancer effect of ONO-5046 Na was measured by monotetrazolium assay. RESULTS: Hepatic ischaemia-reperfusion increased the number of liver metastases of RCN-H4 in both clamped and unclamped hepatic lobes. ONO-5046 Na significantly inhibited this in unclamped lobes, but had no anti-cancer effect. CONCLUSION: Neutrophil elastase may have an important role in increasing haematogenous liver metastases by ischaemia-reperfusion, particularly in unclamped lobes.