Asymmetrical interhemispheric fiber tracts in patients with hemimegalencephaly on diffusion tensor magnetic resonance imaging.

OBJECTIVE: The internal structures of cerebral white matter in patients with hemimegalencephaly have not yet been investigated except for one, which evaluated aberrant fibers. We examined interhemispheric fiber tracts (FT) passing through the corpus callosum using magnetic resonance (MR) diffusion tensor imaging (DTI). METHODS: MR studies, including DTI, were performed in nine consecutive patients with hemimegalencephaly and in 11 patients with West syndrome as disease controls. The interhemispheric FT passing through the corpus callosum were evaluated in six regional geometric subdivisions in every hemimegalencephaly and West syndrome patient (54 and 66 subregions, respectively), and the distribution and volume differences between affected and unaffected hemispheres were all compared. RESULTS: In patients with hemimegalencephaly, interhemispheric FT were symmetrically distributed in 27 (50%) of the 54 corpus callosum subregions. However, the FT were distributed to different areas in the same lobes in 22 (40%) subregions, and to different lobes in five (9%) subregions. FT volumes were symmetrical in 35 (65%) subregions, while FT volumes on the affected side were greater, but less than those on the unaffected side, in 14 (26%) and five (9%) subregions, respectively. In contrast, in the West syndrome patients, interhemispheric FT showed symmetrical distributions and volumes in all regions. CONCLUSION: Asymmetrical interhemispheric FT are often observed in patients with hemimegalencephaly, and DTI was a useful means of elucidating the internal structures of white matter.

Prevention of corticosteroid-induced osteonecrosis in rabbits by intra-bone marrow injection of autologous bone marrow cells.

OBJECTIVES: Femoral head osteonecrosis (ON) is a serious complication of steroid administration. We evaluated bone marrow transplantation (BMT) for preventing corticosteroid-induced ON. METHODS: Rabbits, injected with methylprednisolone (MPSL; 20 mg/kg), were divided into four groups: (i) MPSL alone; MPSL injection only, (ii) MPSL+needling; 2 days after MPSL injection, a hole (1.2 mm diameter) was drilled from the outer cortex 2.5 cm distal to the proximal end of the greater trochanter, (iii) MPSL+saline; 2 days after MPSL injection, 2 ml saline was injected directly into the bone marrow cavity, and (iv) MPSL+BMT; 2 days after MPSL injection, 1 x 10(7)/2 ml bone marrow cells (BMCs) were injected directly into the bone marrow cavity. Platelets, fibrinogen, prothrombin time and total cholesterol in peripheral blood were measured before and after treatment. Tissues were stained with haematoxylin and eosion and terminal deoxynucleotidyl-mediated deoxyuridine triphosphate nick-end labelling stain and immunostained for VEGF, while cell proliferation and viability of whole BMCs in the femur were analysed by cell cycle analysis and [(3)H]-thymidine uptake. RESULTS: The ON incidence in rabbits treated with MPSL alone, MPSL+needling and MPSL+saline was 72.7, 70.0 and 66.7%, respectively, while in the MPSL+BMT group, the incidence was 0%. Serological findings in the MPSL+BMT group were almost normalized. VEGF and TUNEL staining were reduced in the MPSL+BMT group compared with all other groups. There were significantly fewer BMCs in G1 phase from the MPSL+BMT group than the other groups, while uptake of [(3)H]-thymidine was significantly increased. CONCLUSION: Direct injection of autologous BMCs into femurs prevents corticosteroid-induced ON following treatment with high-dose, short-term steroids.

Possible association between nonsynonymous polymorphisms of the anaplastic lymphoma kinase (ALK) gene and schizophrenia in a Japanese population.

We examined, for the first time, the possible association between schizophrenia and the anaplastic lymphoma kinase (ALK) gene which plays an important role in neurodevelopment. When two nonsynonymous polymorphisms (Arg1491Lys and Glu1529Asp) were examined, there were significant differences in genotype and allele distributions between patients and controls. Individuals homozygous for the minor allele (1491Lys-1529Asp) were more common in patients than in controls (p = 0.0064, odds ratio 2.4, 95% CI 1.3-4.6). These results suggest that genetic variations of the ALK gene might confer susceptibility to schizophrenia.

Identification of a novel plant-specific kinesin-like protein that is highly expressed in interphase tobacco BY-2 cells.

Through reverse transcription-polymerase chain reaction and Northern blot analysis, we identified TBK5, a novel plant-specific kinesin-like protein (KLP) that is highly expressed in interphase tobacco BY-2 cells. TBK5 mRNA was present at a high level throughout the growth cycle, even in cells that had entered the stationary phase, where cell proliferation had ceased. However, transcripts for five other tobacco KLPs that we have identified were preferentially expressed in mitotic cells, and either not or only slightly accumulated in cells that had entered the stationary phase. Thus, TBK5 appears to be a KLP whose cellular function most closely relates to the cortical array of microtubules that plays a key role in plant cell morphogenesis. The predicted structure of TBK5 is characterized by a central motor domain that is phylogenetically distant from those of other reported KLPs, coiled-coil domains located on both sides of the motor domain, and a basic C-terminal domain. In addition, TBK5 has a putative neck domain which is closely related to the neck domain of KLPs with C-terminal motor domains, previously shown to control the direction of KLP movement towards the minus ends. Antibodies against truncated TBK5 recognized a polypeptide with a molecular mass of 74 kDa in cytoplasmic extracts of interphase cells, and this polypeptide cosedimented with microtubules assembled in the cytoplasmic extracts. The 74 kDa polypeptide corresponding to TBK5 dissociated from microtubules with high concentrations of NaCl but was not dissociated by MgATP. We hypothesize that TBK5 functions in the regulation of the arrangement of cortical microtubules.

Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease.

UNLABELLED: The aim of this SPECT study was to investigate the effects of donepezil on regional cerebral blood flow (rCBF) in patients with mild to moderate Alzheimer's disease (AD) using statistical parametric mapping. METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer in 35 AD patients with a Mini-Mental State Examination score > 16 on initial evaluation. Baseline and follow-up SPECT studies with a mean interval of 12 mo were performed on these patients. We used the adjusted rCBF images in the relative flow distribution (normalization of global cerebral blood flow for each patient to 50 mL/100 g/min with proportional scaling) to compare these groups through statistical parametric mapping. RESULTS: In the follow-up study, the adjusted rCBF was significantly preserved in the right and left anterior cingulate gyri, right middle temporal gyrus, right inferior parietal lobules, and prefrontal cortex of donepezil-treated AD patients, compared with placebo-treated AD patients. CONCLUSION: Treatment with donepezil for 1 y appears to reduce the decline in rCBF, suggesting preservation of functional brain activity.

Mitral valve replacement through right thoracotomy after coronary arterial bypass grafting with functioning conduits.

A 67-year-old man who had undergone coronary artery bypass grafting 3 years previously suffered from severe mitral regurgitation associated with Streptococcal infective endocarditis. He was placed in New York Heart Association functional class III. Preoperative angiography demonstrated good opacification of all 3 conduits implanted in the previous operation. We replaced the mitral valve through an anterolateral right thoracotomy, approaching the mitral valve as an alternative to redoing sternotomy to minimize potential injury to patent grafts. His postoperative course was uneventful. After a 1-month course of antibiotics, the patient was discharged as New York Heart Association class II and at present, 3 months after discharge, is doing well. This approach is an effective alternative to redoing sternotomy for mitral valve operation, especially in patients undergoing a previous coronary arterial bypass grafting via median sternotomy.

Development status of Terumo implantable left ventricular assist system.

We have been developing an implantable left ventricular assist system (T-ILVAS) featuring a magnetically suspended centrifugal pump (MSCP) since 1995. In vitro and in vivo studies using a prototype MSCP composed of a polycarbonate housing and impeller (196 ml) have demonstrated long-term durability and excellent blood compatibility for up to 864 days, and excellent stability of the magnetic bearing of the MSCP. These preliminary results strongly suggested that the magnetic bearing of the MSCP is reliable and is a most feasible mechanism for a long-term circulatory assist device. We have recently devised a clinical version pump made of titanium (180 ml) with a new position sensor mechanism and a wearable controller with batteries. Cadaver fit study confirmed that the Type IV pump could be implanted in a small patient with a body surface area as small as 1.3. The in vitro performance tests of the Type IV pump demonstrated excellent hydrodynamic performances with an acceptable hemolysis rate. New position sensors for the titanium housing showed more uniform sensor outputs of a magnetic bearing than in the prototype polycarbonate pump. The Type IV pump then was evaluated in vivo in 6 sheep at the Oxford Heart Centre. Four sheep were electively sacrificed at 3 months and were allowed to survive for more than 6 months for long-term evaluation. In this particular series of experiments, no anticoagulant/antiplatelet regimen was utilized except for a bolus dose of heparin during surgery. There was a left ventricular mural thrombi around the inflow cannula in 1 sheep. Otherwise, there was no mechanical failure nor sign of thromboembolism throughout the study.

The NPK1 mitogen-activated protein kinase kinase kinase is a regulator of cell-plate formation in plant cytokinesis.

Mitogen-activated protein kinase (MAPK) cascades play important roles not only in the transduction of extracellular signals but in the progression of the cell cycle. However, evidence for their role in cytokinesis is limited. Here, we show that a tobacco MAPK kinase kinase (MAPKKK), designated NPK1, is required for cytokinesis. The activity of NPK1 increases in the late M phase of the tobacco cell cycle. During expansion of a new cross-wall (cell plate) toward the cell cortex, NPK1 is consistently localized to the equatorial zone of the phragmoplast, the cytokinetic apparatus where the cell plate is formed. Expression of a kinase-negative mutant of NPK1 results in the generation of multinucleate cells with incomplete cell plates. Phragmoplasts can be formed, but its expansion toward the cell cortex is also blocked. Thus, our results indicate that the NPK1 MAPKKK is essential for the formation of the cell plate, especially for its lateral growth.

Skeletonization and harvest of the internal thoracic artery with an ultrasonic scalpel.

A new method to skeletonize and harvest the internal thoracic artery using an ultrasonic scalpel is presented. The technique is simple, safe, and minimally invasive. It is possible to obtain sufficient vessel length for anastomosis to most coronary arteries for bypass grafting.

[Management of coronary artery disease combined with aortic stenosis: how to do with mild aortic stenosis].

A total of fourteen patients with combined operation of coronary artery bypass grafting (CABG) and aortic valve replacement (AVR) for coronary artery disease (CAD) and aortic stenosis (AS) were reviewed to evaluate the indication of the combined operation. Preoperative pressure gradient across the valve and effective orifice area were 21-89 mmHg (mean 64 mmHg), 0.5-1.9 cm2 (mean 0.92 cm2), respectively. The extent of CAD was 1-3 (mean 2.0). Fractional shortening (%FS) ranged from 13% to 43% with mean value of 28%. All patients underwent CABG and AVR. The number of grafts was 1-4 (mean 2.3) with internal thoracic artery used in 7 cases. Mechanical valves were employed for all patients except 1 case with cerebral aneurysm. There was no operative death, although low output syndrome developed in 2 cases. One had poor left ventricular function preoperatively, and the other was emergency case. Fractional shortening improved postoperatively even in two cases with preoperative %FS less than 20%, and all grafts were patent on postoperative coronary angiography. The event-free survival was 100% during 32 months of mean follow-up. Combined AVR with CABG is recommended to avoid risky secondary operation in patients of CAD and AS, even if one of which is relatively mild, because of the fact that operative and late results of the combined surgery are satisfactory.

Coronary artery bypass grafting using the "Super Pulse" dynamic pulsatile cardiopulmonary bypass device in patients with cerebrovascular occlusive disease.

Patients with coronary disease complicated by severe carotid or intracranial arterial stenosis underwent coronary artery bypass graft surgery (CABG) using a novel method of dynamic pulsatile cardiopulmonary bypass (Super Pulse CPB). The Super Pulse technique can maintain the systolic pressure and systolic-diastolic amplitude in such a way that they mimic the physiologic circulation. Forty-five patients (33 males and 12 females, mean age 65.1 years) with coronary disease who had a greater than 75% stenosis of the carotid or intracranial arteries were evaluated. Evaluation was performed for the following 3 groups: 8 patients with conventional pulsatile CPB (Group I), 8 patients with conventional pulsatile CPB plus intraaortic balloon pumping (Group II), and 29 patients with Super Pulse CPB. Maximum, minimum, and mean perfusion pressures during CPB were 112.7, 53.6, and 76.9 mmHg (integrated mean), respectively, in Group III. The systolic-diastolic amplitude was significantly better than for Group I and similar to baseline pressures. No patients in Group II or Group III developed perioperative cerebral disorders or myocardial infarction, while in Group I perioperative cerebral disorders developed in 3 patients, myocardial infarction occurred in 2 patients, and 2 patients died during hospitalization. The initial performance of the Super Pulse CPB indicates excellent safety, and is useful for patients with co-morbid cerebral arterial disease.

Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT.

UNLABELLED: The aim of this SPECT study was to determine the initial abnormality and longitudinal changes in regional cerebral blood flow (rCBF) in early Alzheimer's disease (AD) using statistical parametric mapping (SPM). METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer SPECT in 32 patients complaining of mild cognitive impairment, with a Mini-Mental State Examination score more than 24 at the initial study, and 45 age-matched healthy volunteers. All patients satisfied the diagnostic criteria of AD during the follow-up period of at least 2 y. Follow-up SPECT studies were performed on the patients at a mean interval of 15 mo. We used the raw data (absolute rCBF parametric maps) and the adjusted rCBF images of relative flow distribution (normalization of global cerebral blood flow [CBF] for each subject to 50 mL/100 g/min with proportional scaling) to compare these groups with SPM. RESULTS: In the baseline study, the adjusted rCBF was significantly and bilaterally decreased in the posterior cingulate gyri and precunei of patients compared with healthy volunteers. In the follow-up study, selected reduction of the adjusted rCBF was observed in the left hippocampus and parahippocampal gyrus. These areas showed the most prominent reduction in absolute rCBF on each occasion. Moreover, further decline of the absolute rCBF was longitudinally observed in extensive areas of the cerebral association cortex. CONCLUSION: SPM analysis showed the characteristic early-AD rCBF pattern of selective decrease and longitudinal decline, which may be overlooked by a conventional region-of-interest technique with observer a priori choice and hypothesis. This alteration in rCBF may closely relate to the pathophysiologic process of this disease.

[Effects of healthy aging on the regional cerebral blood flow measurements using 99mTc-ECD SPECT assessed with statistical parametric mapping].

To clarify the effects of normal aging on the cerebral blood flow, regional cerebral blood flow measurements++ using a Patlak Plot method of 99mTc-ECD were performed in 53 normal volunteers aged 18 to 87 years old (mean = 47.9 years). The subjects, 29 men and 24 women, were normal on clinical examination, and had neither a history of neurological nor psychiatric disease and no abnormal CT or MRI images. Statistical parametric mapping (SPM) was used for automatching and an objective approach to analysis of SPECT image data. Global cerebral blood flow showed a significant decline with age (r = 0.406). The SPM analysis (voxel height; p < 0.001, Bonferroni correction; p < 0.05) demonstrated significant age-related decrease of relative rCBF in prefrontal cortices, anterior cingulate giri, and insular cortices-temporal poles bilaterally, these affected areas belonged to limbic or association cortices. Therefore, these decreases in rCBF may suggest cognitive changes that occur during normal aging.

Minimally invasive direct coronary artery bypass grafting using the gastroepiploic artery for reoperation after the Cabrol procedure.

Obstruction of the right coronary ostial anastomosis is a rare late complication after composite graft replacement of the ascending aorta and the aortic valve with separate Dacron coronary grafts (Cabrol method). Occlusion at the right coronary ostial anastomosis in a 36-year-old woman with aortitis syndrome who underwent a composite graft with a Dacron coronary graft is described. She underwent a third successful operation for right coronary reconstruction by minimally invasive direct coronary artery bypass grafting technique using the right gastroepiploic artery. This approach is likely to be extremely useful in avoiding resternotomy and cardiopulmonary bypass in patients requiring coronary reoperation.

Evidence for functional abnormality in the right auditory cortex during musical hallucinations.

Right auditory cortex dysfunction during musical hallucinations occurred in an 88-year-old woman, who was otherwise cognitively intact. We assessed this phenomenon with a combination of neuromagnetic and cerebral blood-flow measurements.

Retrograde cerebral perfusion versus selective cerebral perfusion as evaluated by cerebral oxygen saturation during aortic arch reconstruction.

BACKGROUND: Time limits for neuroprotection by retrograde cerebral perfusion (RCP) and selective cerebral perfusion (SCP) in aortic arch aneurysm repair or dissection are undergoing definition. METHODS: Using near-infrared optical spectroscopy, changes in regional cerebrovascular oxygen saturation (rSO2) were compared between the two perfusion methods. RESULTS: Immediately before cardiopulmonary bypass, baseline rSO2 was 63.9%+/-6.9% for the RCP and 66.1%+/-5.3% for the SCP group (no significant difference). As patients were core-cooled to 20 degrees C, rSO2 increased to 73.1%+/-8.8% and 74.1%+/-7.9% in the RCP and SCP groups, respectively. With circulatory arrest, rSO2 suddenly decreased. After starting cerebral perfusion, rSO2 returned to prearrest values in the SCP group but continued decreasing steadily in the RCP group, to levels below baseline after about 25 minutes. At the end of perfusion, rSO2 was 57.4%+/-12.2% for the RCP group and 71.7%+/-6.9% for the SCP group, and the ratio of rSO2 to baseline value was 0.89 for RCP and 1.08 for SCP despite a shorter brain perfusion time for RCP (38.8+/-18.0 versus 103.3+/-43.3 minutes). Three of 5 patients whose ratios of rSO2 to baseline at the end of brain protection were 0.7 or less had neurologic deficits. CONCLUSIONS: Although SCP showed no clinically important time limitation, rSO2 continued to decrease with time during RCP. An rSO2 ratio less than 0.7 could represent a critical lower limit.

Plasma membrane-associated actin in bright yellow 2 tobacco cells. Evidence for interaction with microtubules

Plasma membrane ghosts form when plant protoplasts attached to a substrate are lysed to leave a small patch of plasma membrane. We have identified several factors, including the use of a mildly acidic actin stabilization buffer and the inclusion of glutaraldehyde in the fixative, that allow immunofluorescent visualization of extensive cortical actin arrays retained on membrane ghosts made from tobacco (Nicotiana tabacum L.) suspension-cultured cells (line Bright Yellow 2). Normal microtubule arrays were also retained using these conditions. Membrane-associated actin is random; it exhibits only limited coalignment with the microtubules, and microtubule depolymerization in whole cells before wall digestion and ghost formation has little effect on actin retention. Actin and microtubules also exhibit different sensitivities to the pH and K+ and Ca2+ concentrations of the lysis buffer. There is, however, strong evidence for interactions between actin and the microtubules at or near the plasma membrane, because both ghosts and protoplasts prepared from taxol-pretreated cells have microtubules arranged in parallel arrays and an increased amount of actin coaligned with the microtubules. These experiments suggest that the organization of the cortical actin arrays may be dependent on the localization and organization of the microtubules.