A new method for evaluation of fracture healing by echo tracking

Assessment of bone healing on radiographs depends on the volume and radio-opacity of callus at the healing site, but is not necessarily objective, and there are differences of judgment among observers. To overcome this disadvantage, a clinical system was developed to quantify the stiffness of healing fractures of the tibia in patients by the echo tracking (ET) method in a manner similar to a three-point bending test. The purpose of this study was to ensure that the ET system could clinically assess the progress, delay or arrest of healing. The fibular head and the lateral malleolus were supported. A 7.5-MHz ultrasound probe was placed on the proximal and distal fragments and a load of 25 N was applied. Five tracking points were set along the long axis of the ultrasound probe at intervals of 10 mm. With a multiple ET system, two probes measured the displacement of five tracking points on each of the proximal and distal fragments of the tibia, thereby detecting the bending of the two fragments generated by the load. ET angle was defined as the sum of the inclinations of the proximal and distal fragments. Eight tibial fractures in seven patients treated by a cast or internal fixation were measured over time. In patients with radiographically normal healing, the bending angle decreased exponentially over time. However, in patients with nonunion, the angle remained the same over time. It was demonstrated that the ET method could be clinically applicable to evaluate fracture healing as a versatile, quantitative and noninvasive technique. (E-mail: ohnishii-dis@h.u-tokyo.ac.jp)     

Configurational factors in the perception of faces and non-facial objects: an ERP study

During the viewing of human faces, it is easier to recognize detailed features if the face is presented in an unusual configuration; for example, a split face. The present study used electroencephalography to investigate the brain activity elicited in response to a neutral, inverted, and split face and compared this to the activity produced in response to a non-facial stimulus (a clock). Results showed that the N170 response amplitude was larger and its latency longer during recognition of split and inverted faces as compared to a normal face, whereas no amplitude change was seen for the different clock configurations. However, for the P300 component, larger amplitudes were observed in both the face and the object condition. Taken together, the results suggest that unusual human face presentations are detected at earlier stages than unusual object presentations.     

A case of craniotomy with intermittent tracheal extubation for speech mapping during surgery

We gave anesthesia for craniotomy in a 54-year-old man with intracranial tumor near the Broca speech centers causing facial nerve palsy and slight allophasis. Nasotracheal intubation was performed after intravenous administration of droperidol 15 mg and fentanyl 0.2 mg. The head was fix with 3 pins with the patient in the right lateral position, and endotracheal tube was withdrawn to the pharynx confirming the speech of the patient. The patient was intubated again using fiberscope after intravenous midazolam 3 mg with inhalation of nitrous oxide. Nitrous oxide was discontinued for 2 hours after the start of surgery for the speech mapping, and the patient emerged from anesthesia in 5 minutes. He pronounced the letters on cards during the speech mapping. After the successful mapping, the patient was intubated again using fiberscope after administration of fentanyl 0.1 mg. Anesthesia was maintained again with nitrous oxide. The patient recovered from anesthesia quickly after surgery without any events. On the post-operative round, the patient could not remember well the anesthetic induction and the awakening during the brain mapping. Three episodes of intubation caused no complications, and the neurological symptoms disappeared in several days.     

Phosphoprotein analysis for investigation of in vivo relationship between protein phosphatase inhibitory activities and acute hepatotoxicity of microcystin-LR

Microcystin-LR (MCLR) produced by freshwater cyanobacteria is a potent hepatotoxin and inhibits protein serine/threonine phosphatases 1 and 2A (PP1 and PP2A). Okadaic acid (OA) is a similar phosphatase inhibitor, which has less affinity to PP1 than PP2A. MCLR and OA behave similarly with primary culture hepatocytes with the induction of phosphorylation of the cytokeratins, morphological changes, and apoptosis. The purpose of this study was to investigate the in vivo relationship between the protein phosphatase inhibitory activities and the acute hepatotoxicity of MCLR compared to OA. MCLR and OA were intraperitoneally administrated to mice at approximately 220 microg/kg. After 30 min, the liver of only the MCLR-treated mouse was dark-colored and heavier than that of the control mouse. Subsequently, the phosphoproteins of the mouse liver were chemically modified with reversible biotinylation reagent and selectively analyzed by LC/MS/MS. Consequently, the phosphorylated Ser 354 of formyltetrahydrofolate dehydrogenase, which is an abundant enzyme in the liver cytoplasm, was observed in the MCLR- and the OA-treated mice 9.5 and 5.3 times more intensely than in the control mouse respectively, suggesting that MCLR and OA inhibited PP2A and induced the resulting phosphorylation. These results supported the hypothesis that the acute hepatotoxicity is possibly caused by the PP1 inhibition, and not by the PP2A inhibition.     

Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation

The Bcl-2 antagonist ABT-737 targets Bcl-2/Bcl-xL but not Mcl-1, which may confer resistance to this novel agent. Here, we show that Mcl-1 down-regulation by the cyclin-dependent kinase (CDK) inhibitor roscovitine or Mcl-1-shRNA dramatically increases ABT-737 lethality in human leukemia cells. ABT-737 induces Bax conformational change but fails to activate Bak or trigger Bax translocation. Coadministration of roscovitine and ABT-737 untethers Bak from Mcl-1 and Bcl-xL, respectively, triggering Bak activation and Bax translocation. Studies employing Bax and/or Bak knockout mouse embryonic fibroblasts (MEFs) confirm that Bax is required for ABT-737+/-roscovitine lethality, whereas Bak is primarily involved in potentiation of ABT-737-induced apoptosis by Mcl-1 down-regulation. Ectopic Mcl-1 expression attenuates Bak activation and apoptosis by ABT-737+roscovitine, whereas cells overexpressing Bcl-2 or Bcl-xL remain fully sensitive. Finally, Mcl-1 knockout MEFs are extremely sensitive to Bak conformational change and apoptosis induced by ABT-737, effects that are not potentiated by roscovitine. Collectively, these findings suggest down-regulation of Mcl-1 by either CDK inhibitors or genetic approaches dramatically potentiate ABT-737 lethality through cooperative interactions at two distinct levels: unleashing of Bak from both Bcl-xL and Mcl-1 and simultaneous induction of Bak activation and Bax translocation. These findings provide a mechanistic basis for simultaneously targeting Mcl-1 and Bcl-2/Bcl-xL in leukemia.     

Parameter Predicting the Recurrence of Adhesive Small Bowel Obstruction in Patients Managed with a Long Tube

Introduction Some of our patients showed a recurrence of adhesive small bowel obstruction (ASBO) with nonoperative management. The aim of this study was to evaluate the parameters predicting the recurrence of ASBO in patients managed with a long tube. Methods Of 234 patients with ASBO admitted from April 1998 to September 2002, a total of 91 who recovered with nonoperative management after long tube placement were enrolled in this retrospective clinical study. We divided them into two groups for follow-up: the recurrence group and the no-recurrence group. We compared baseline characteristics, the number of previous ASBO admissions, the number of abdominal operations, the interval from the onset of symptoms to long-tube insertion, the duration of long-tube placement, the type of the contrasted intestine through the long tube, the location of the long-tube tip, and the drainage volume through the long tube between the two groups. We then examined the cumulative recurrence rate. Results A significant difference was found in the number of previous ASBO admissions, the duration of long-tube placement (77 hours vs. 43 hours), the contrasted intestine through the long tube, and the location of the long-tube tip. By multivariate analysis, the duration of long-tube placement was an independent parameter predicting the recurrence of ASBO. Conclusions These results suggest that the duration of long-tube placement might serve as a parameter for predicting recurrence of ASBO in patients managed with a long tube.     

Connection between a dural artery and a dural vein in a dural arteriovenous fistula of the cranial vault

A 41-year-old man presented with consciousness disturbance and right hemiparesis. Computed tomography showed a hematoma in the frontal lobe. Left carotid angiography showed a dural arteriovenous fistula (AVF) located in the cranial vault, supplied by the left middle meningeal artery, and drained directly into the cortical vein adjacent to the superior sagittal sinus. Emergency decompressive craniectomy and evacuation of the intracerebral hematoma were performed. A red vein was found on the cortex but the location of the arteriovenous shunt was not clear due to severe brain swelling. Two months later, cranioplasty was performed and a part of the dura mater, expected to have been affected by the dural AVF, was resected. Histological examination disclosed thickening of the intima of the middle meningeal artery and a few small veins around this artery. The fistula was clearly demonstrated between the dural artery and the dural vein. The non-sinal type of dural AVF may originate in similar arteriovenous connections to the sinal type.     

Role of Tyr306 in the C-terminal fragment of Clostridium perfringens enterotoxin for modulation of tight junction

We previously reported that the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) is a novel type of absorption enhancer that interacts with claudin-4 and that Tyr306 of C-CPE plays a role in ability of C-CPE to modulate barrier of tight junctions. In the current study, to investigate effects of Tyr306 on the C-CPE activity, we prepared some C-CPE mutants substituted Tyr306 with Trp (Y306W), Phe (Y306F) and Lys (Y306K). We found that Y306W and Y306F mutants of C-CPE had claudin-4 binding affinities and effects on the barrier function of tight junctions, whereas both of these properties were greatly reduced with the Y306K mutant. Finally, the Y306K but not the Y306F and Y306W mutants had reduced abilities to enhance absorption in rat jejunum. These results indicate that aromatic and hydrophobic properties, not hydrogen bonding potential, of Tyr306 are involved in the interaction of C-CPE with claudin-4 and in the modulation of the tight junction barrier function by C-CPE.     

Involvement of the sigma1 receptor in inhibiting activity of fluvoxamine on marble-burying behavior: comparison with paroxetine

In the present study, we examined the involvement of the sigma1 receptor in the inhibitory effect of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine, compared with that of paroxetine, on marble-burying behavior, which is an animal model of obsessive-compulsive disorder. Sigma1 receptor agonists (+)-SKF 10047 and PRE-084 significantly inhibited marble-burying behavior. Sigma receptor antagonist BD 1047 and selective sigma1 receptor antagonist BD 1063 significantly attenuated the inhibition of marble-burying behavior by fluvoxamine. In contrast, selective sigma2 receptor antagonist SM-21 failed to affect the inhibition of marble-burying behavior by fluvoxamine. On the other hand, BD 1047 and BD 1063 had no effect on the inhibition of marble-burying behavior by paroxetine. These observations show that activation of the sigma1 receptor is a necessary component in the inhibitory effect of fluvoxamine on marble-burying behavior, and that the mechanism of its action is clearly different from that of paroxetine.     

Nodular glomerulosclerosis in patients without any manifestation of diabetes mellitus

AIM/METHODS: Diabetic nodular glomerulosclerosis is considered to be the specific renal lesion of diabetes mellitus (DM). However, some cases, in which nodular glomerulosclerosis was found without any manifestation of DM, have also occasionally been reported. We clinicopathologically examined seven cases without a prior history of DM. They consisted of six men and one woman with a mean age of 57 years, and included three cases with family history of DM and six cases with hypertension. RESULTS: Mean body mass index was 26.2 +/- 5.9 (means +/- SD) kg/m(2) and haemoglobin A1c 5.3 +/- 1.1% or haemoglobin A1 7.0 +/- 0.6%. Mean plasma glucose levels were 5.3 +/- 0.7 mmol/L at fasting and 10.1 +/- 1.9 mmol/L at 2 h of 75 g OGTT (normal: 1 patient; impaired glucose tolerance: 4 patients; DM: 2 patients). None of them showed diabetic retinopathy in fundoscopic ophthalmoscopy. Mean serum creatinine was 268 +/- 215 micromol/L, urinary protein 5.2 +/- 4.0 g/day, and three patients had mild haematuria. Renal biopsy revealed typical nodular glomerulosclerosis, a negative deposition based on an immunofluorescence study, and neither any significant electron dense deposits nor fibrils on electron microscopy. CONCLUSION: These patients at presentation had no overt clinical manifestations of glucose intolerance. Diabetic nodular glomerulosclerosis can occur in patients without overt DM, suggesting the role of factors additional to prolonged hyperglycaemia in the pathogenesis of this disorder.