Imaging Molecular Motion: Femtosecond X-Ray Scattering of an Electrocyclic Chemical Reaction.

Structural rearrangements within single molecules occur on ultrafast time scales. Many aspects of molecular dynamics, such as the energy flow through excited states, have been studied using spectroscopic techniques, yet the goal to watch molecules evolve their geometrical structure in real time remains challenging. By mapping nuclear motions using femtosecond x-ray pulses, we have created real-space representations of the evolving dynamics during a well-known chemical reaction and show a series of time-sorted structural snapshots produced by ultrafast time-resolved hard x-ray scattering. A computational analysis optimally matches the series of scattering patterns produced by the x rays to a multitude of potential reaction paths. In so doing, we have made a critical step toward the goal of viewing chemical reactions on femtosecond time scales, opening a new direction in studies of ultrafast chemical reactions in the gas phase.

Quantitative analysis of amyloid plaques in a mouse model of Alzheimer's disease by phase-contrast X-ray computed tomography.

Densely aggregated beta-amyloid peptides are believed to play a key role in the pathogenesis of Alzheimer's disease. Amyloid plaques are a potential target for molecular imaging to determine the clinical status of Alzheimer's disease. Phase-contrast X-ray imaging combined with computed tomography is a promising technique that can be used to visualize the physical density of structures in biological tissues non-invasively, and without the use of imaging agents. Using brain tissue isolated from a mouse model of Alzheimer's disease, we show that beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques, but not beta-amyloid 40-negative/beta-amyloid 42-positive amyloid plaques, exist as high-density aggregates that can be specifically detected by phase-contrast X-ray computed tomography. The phase-contrast X-ray computed tomography detected beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques in three-dimensions with an extremely high sensitivity comparable to that of histological analysis, and also enabled the load of amyloid plaques to be quantified. Furthermore, the use of phase-contrast X-ray computed tomography reveals that the physical density of beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques increases with age, and that the large volume, high-density, amyloid plaques that are specifically observed in aged Alzheimer's disease mice are closely associated with neuritic dystrophy. These results demonstrate that phase-contrast X-ray computed tomography is a highly sensitive imaging technique for analyzing dense-cored amyloid plaques in postmortem samples, and is beneficial in elucidating amyloid pathophysiology in Alzheimer's disease.

Effects of 4-methylcatechol, a stimulator of endogenous nerve growth factor synthesis, on experimental acrylamide-induced neuropathy in rats.

Acrylamide monomer (ACR) causes central-peripheral distal axonopathy. We induced neuropathy in rats by means of ACR injection as an experimental model of the dying-back type of peripheral neuropathy to assess the potential efficacy of 4-methylcatechol (4-MC), a potent stimulator of endogenous nerve growth factor (NGF) synthesis, as a therapeutic agent for the axonal nerve lesion. ACR-induced neuropathy in rats resulted in a dying- back type of axonal degeneration, and a statistically significant reduction in motor nerve conduction velocity (MNCV), and density of large myelinated fibers. We administered 4-MC and ACR together to rats intraperitoneally and found improved clinical signs, and significantly more NGF content in sciatic nerves, faster MNCV, and greater myelinated fiber density than in rats given ACR alone. These findings suggest that 4-MC can prevent the progression of ACR-induced neuropathy and decreased NGF levels may be involved in the pathogenesis of ACR neuropathy.

Tethered cord syndrome: ventral displacement of the spinal cord at the thoracolumbar junction in magnetic resonance imaging.

PURPOSE: To determine the route of the spinal cord at the thoracolumbar junction in a sagittal MRI taken in the supine position in tethered cord syndrome. PATIENTS AND METHODS: We retrospectively studied the MRIs of 11 cases with tethered cord syndrome and the MRIs of 33 individuals without spina bifida were used as a control. When the anteroposterior diameter of the low intensity area behind the spinal cord on the sagittal T1 weighted images taken in the supine position was more than one third the anteroposterior diameter of the cord at T12/L1, the spinal cord was defined as being displaced ventrally. RESULTS: Ventral displacement was found in 6 cases (VD group), but not in the rest (non-VD group). None of the control group showed ventral displacement. There was a tendency for motor weakness to be more severe in the VD group. CONCLUSION: In some cases with tethered cord syndrome, the spinal cord takes a ventral route at the thoracolumbar junction even on MRI taken in the supine position. This finding may be useful in predicting the severity of the motor weakness in the lower extremity.

Posterior spinal shortening for paraplegia after vertebral collapse caused by osteoporosis.

STUDY DESIGN: Case report of a patient who underwent a new surgical procedure for paraplegia after vertebral collapse due to osteoporosis. OBJECTIVES: To propose a new approach to posterior spinal fusion surgery for osteoporotic patients. SUMMARY OF BACKGROUND DATA: Surgical treatment was performed on a paraplegic patient after vertebral collapse due to osteoporosis. However, the surgery was difficult because implants such as hooks and screws often dislodged during the treatment. The poor holding power of these implants to the osteoporotic spine is a challenging problem in this treatment. METHODS: When a fractured vertebra is shortened by resecting the posterior part of the spine and the application of a compression force, a short vertebra is produced. As a result, the thoracic kyphosis decreases and the force pushing the upper thoracic spine inferio-ventrally also decreases. RESULTS: A 74-year-old woman with T12 vertebral collapse was treated with this new method. Lateral Cobb angle (T10-L2) was reduced from 26 to 4 degrees after surgery. The shortened vertebral body united, and after 33 months, the implant had not dislodged and no loss of correction was seen. CONCLUSION: The posterior spinal shortening can be a choice for treating delayed paraplegia after osteoporotic vertebral fracture.

Bone mineral density in patients with ossification of the posterior longitudinal ligament. Minimal decrease of bone mineral density with aging.

STUDY DESIGN: Bone mineral density of individuals with ossification of the posterior longitudinal ligament and that of normal people was determined by dual-energy x-ray absorptiometry. OBJECTIVES: To determine whether bone mineral density in the people with ossification of the posterior longitudinal ligament is higher than that in normal individuals even in body parts other than the spine, and to evaluate the relation between bone mineral density and age in patients with ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: It is unknown whether the bone mineral density of patients with ossification of the posterior longitudinal ligament is greater in body parts other than the spine. If so, it provides a basis for the theory that certain systemic factors are involved in the pathogenesis of ossification of the posterior longitudinal ligament. Because bone mineral density decreases physiologically after middle age, the influence of age must be considered in evaluating bone mineral density. METHODS: In the rib area and upper and lower limb areas, which are not affected by ossification of the spinal ligament, bone mineral density of 45 men with ossification of the posterior longitudinal ligament of the cervical spine was compared with that of 25 men without ossification of the posterior longitudinal ligament (normal group). RESULTS: Bone mineral density was higher in the group with ossification of the posterior longitudinal ligament in each part and significantly higher in the rib and lower limb areas (rib: P < 0.01, lower limb: P < 0.05). The age-related decrease was significantly less in the group with ossification of the posterior longitudinal ligament (rib: P < 0.01, upper limb: P < 0.05, lower limb: P < 0.01). CONCLUSIONS: Systemic factors that increase bone mineral density appear to be involved in the pathogenesis of ossification of the posterior longitudinal ligament, and these factors may be activated after middle age.

A report on the safety of unilateral vertebral artery ligation during cervical spine surgery.

STUDY DESIGN: This study retrospectively analyzed the outcome of unilateral vertebral artery ligation during cervical spine surgery. OBJECTIVES: To examine the influence of unilateral vertebral artery ligation on the function of brain and spinal cord. SUMMARY OF BACKGROUND DATA: There was little published information about the outcome of a vertebral artery ligation except for several reports from the field of neurosurgery. METHODS: Unilateral vertebral artery ligation was used in 15 patients with cervical tumors of the spine or the spinal cord (age range, 13-71 years; nine male patients and six female). The authors ligated the involved vertebral artery only when the tumor appeared on the minor or equal diameter artery side measured by pre-operative angiogram. The patient's condition was examined regarding signs of dysfunction of the brain stem, the cerebellum, or the spinal cord. RESULTS: Preoperative angiogram showed that the involved vertebral artery had a smaller diameter in four patients and had an equal diameter in 11 patients compared with the one not involved. The involved vertebral artery was severed at single site in four patients and was resected between two distant sites of ligation in 11 patients. Examination after surgery of the patient's condition (follow-up periods ranged from 10 months to 7 years) revealed that unilateral vertebral artery ligation did not provoke any symptoms of damage resulting from ischemia of the brain stem, the cerebellum, or the spinal cord. CONCLUSION: A vertebral artery could be ligated uneventfully when the diameter of the vertebral artery was not larger than the one not involved. Where vertebral artery ligation could not be avoided, it should be confirmed by preoperative angiogram that the other vertebral artery is large enough and that simultaneous occlusion testing of the involved vertebral artery is uneventful.

Trunk muscle weakness as a risk factor for low back pain. A 5-year prospective study.

STUDY DESIGN: A 5-year prospective study. OBJECTIVES: To investigate trunk muscle weakness as a risk factor for low back pain in asymptomatic volunteers. SUMMARY OF BACKGROUND DATA: Muscle strength has not been sufficiently studied as a risk factor for low back pain. METHODS: The study participants included 30 male and 37 female volunteers (mean age, 17 +/- 2 years), who neither reported nor had ever been treated for low back pain. Trunk muscle strength was measured isokinetically (60 degrees/sec), using the trunk extension and flexion and torso rotation units. The peak torques of the volunteers' extension, flexion, rightward rotation, and leftward rotation were measured, and the agonist/antagonist ratios were calculated as extension/flexion and left rotation/right rotation ratio. The volunteers then were followed prospectively for 5 years to determine the incidence of low back pain and were classified into a non-low back pain group (volunteers with no low back pain during the 5-year follow-up period) and a low back pain group (volunteers who experienced low back pain during this period). RESULTS: The low back pain group consisted of 8 male and 10 female volunteers. There were no significant differences between the non-low back pain group and the low back pain group regarding age, height, weight, the peak torque values, or the left rotation/right rotation ratio. However, the extension/flexion ratio of the low back pain group (men, 0.96 +/- 0.27; women, 0.77 +/- 0.19) demonstrated significantly lower values than that of the non-low back pain group (1.23 +/- 0.28 and 1.00 +/- 0.16 for men and women, respectively, P < 0.05). CONCLUSIONS: An imbalance in trunk muscle strength, i.e., lower extensor muscle strength than flexor muscle strength, might be one risk factor for low back pain.

[Laboratory and clinical studies on latamoxef in the field of obstetrics and gynecology].

Latamoxef (LMOX) is a new antibiotic synthesized by Shionogi Research Laboratory. Chemically LMOX is especially unique with a sulfur atom replacing the oxygen atom in the 1 position of the conventional cephalosporin nucleus, and in addition, this antibiotic has a cephamycin-like structure. The antibacterial activity of LMOX shows high potency against Gram-negative bacteria, but tends to be weak against Gram-positive bacteria. The tissue levels of LMOX in humans after intravenous injection of 1 g were examined. The levels in uterine and adnexa uteri tissue at 1 hour after administration were 25.4 and 27.4 micrograms/g respectively. LMOX was administered to 147 cases in infections of obstetric and gynecological field. The clinical effect according to disease was 94.6% for intrauterine infections, 95.0% for adnexitis, 87.0% intrapelvic infections, and 100% for external genital organ infections, making a total of 92.5%. The rate of occurrence of side effects or abnormal laboratory findings was similar to or slightly less than that seen with other beta-lactam antibiotics.

Posterior spinal shortening for paraparesis following vertebral collapse due to osteoporosis.

STUDY DESIGN: Retrospective case series. OBJECTIVES: To assess the efficacy of posterior spinal shortening for paraparetic patients following vertebral collapse owing to osteoporosis, especially on instrumentation loosening. SETTING: Department of orthopaedic surgery, Jichi Medical University Hospital and Omiya Medical Center in Japan. METHODS: The clinical records and radiographs of 13 patients with paraparesis following vertebral collapse owing to osteoporosis treated with posterior spinal shortening were retrospectively reviewed to evaluate the usefulness of this method. Assessment of the clinical course was done by direct examination in all cases. Ambulatory ability was divided into four categories. RESULTS: Upon final observation, nine cases were able to walk with a cane or crutch, one case remained in gait training, two cases remained unable to stand and one case with urinary incontinence improved in urinary function. In one case, paralysis deteriorated. Vertebral compression fracture of the end vertebrae that were fixed occurred in three cases complicated with rheumatoid arthritis. CONCLUSION: The posterior spinal shortening can be a choice for treating delayed paraparesis following vertebral collapse owing to osteoporosis.

A catechol derivative (4-methylcatechol) accelerates the recovery from experimental acrylamide-induced neuropathy.

Acrylamide (ACR) monomer produces neuropathy of the dying-back type and 4-methylcatechol (4-MC) is a potent stimulator of endogenous nerve growth factor synthesis. In the present study, we investigated the efficacy of 4-MC in promoting recovery from experimental ACR neuropathy in rats. Twenty-two Sprague-Dawley rats were made neuropathic by ACR injections. They showed hindlimb paralysis, increment of landing foot spread distance and a statistically significant reduction in motor nerve conduction velocity. After the ACR neuropathy had been established, 12 of the rats were administered 4-MC for 2 weeks, and the other 10 were injected with phosphate-buffered saline alone. 4-MC-administered ACR neuropathy rats showed improvement, i.e., a decrease in landing foot spread distance, increase in motor nerve conduction velocity and increase in nerve growth factor content in the sciatic nerves in comparison with the corresponding values for ACR neuropathy rats given phosphate-buffered saline alone. A decreased number of large myelinated fiber with a reciprocal increase in small myelinated fiber number also was seen in the ACR neuropathy rats; however, this change was ameliorated in part by the administration of 4-MC. Therefore, these findings suggest that 4-MC can accelerate the recovery process clinically, electrophysiologically, biochemically and neuropathologically.

Multiple-level compression myelopathy: concomitant asymptomatic cervical compression adversely affects surgical outcome for thoracic compression myelopathy.

To determine whether asymptomatic spinal cord compression affects surgical outcome for another compression, we retrospectively reviewed the outcome for thoracic myelopathy due to spinal ligament ossification. Improvement assessed by changes in motor function of the lower extremity using the Japanese Orthopedic Association Classification was significantly less in cases associated with asymptomatic cervical ligament ossification (C+T group, N = 5) than in cases without cervical ligament ossification (T group, N = 13) (p < 0.05, Mann- Whitney U test). The "no disability" recovery rate was 61.5% in the T group and none in the C+T group (p < 0.05, Fisher's exact probability test). There was no significant difference in background parameters between the two groups. This study showed that concomitant spinal cord compression, even if asymptomatic itself, can adversely affect surgical outcome at a separate segment.

Expansive cervical laminoplasties--observations on comparative changes in spinous process lengths following longitudinal laminal divisions using autogenous bone or hydroxyapatite spacers.

Expansive laminoplasty is devised to preserve the posterior structures, including the original length of the spinous process which anchors the nucheal muscles, in order to prevent the postoperative development of instability and cervical kyphosis due to structural loss and poor tone of the nucheal muscles, which can result in late neurological regression after laminectomy for cervical myelopathy. We retrospectively compared the length of the spinous process at the time of follow-up with that within 3 months postoperatively using CT images. The shortening was observed in 80% of 60 spinous processes in 13 patients, where a hydroxyapatite (HA) block was used as a spacer placed between the two sides of the split spinous process. The incidence was 9% of 22 spinous processes in six patients where auto bone graft (ABG) was used as a spacer, and the difference was significant (P < 0.01, Chi-square test). Although the usage of HA has the advantage of being less invasive than ABG, it may jeopardize the biomechanical function of nucheal muscles due to reduction in the original length of the spinous process.

Removal of enterogenous cyst of the cervical spine through anterior approach.

Enterogenous cyst is a cause of spinal cord compression. The cyst has been treated surgically through a posterior approach in spite of the location ventral to the spinal cord. We saw two patients who had recurrence at 1 and 3 years after partial removal through this approach. We removed the cyst at the level of the cervical spine in four patients totally or subtotally through an anterior approach. All patients improved neurologically, and there were no signs or symptoms of recurrence at follow-up of from 2 to 13 years (average, 7 years 3 months). It is reasonable to approach the cyst located ventrally to the spinal cord through the anterior route, where the relationship between the cyst wall and the spinal cord can be viewed directly.

Therapeutic effects of aldose reductase inhibitor on experimental diabetic neuropathy through synthesis/secretion of nerve growth factor.

We investigated alterations in nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) contents during treatment with epalrestat, an aldose reductase inhibitor (ARI), on streptozotocin (STZ)-induced diabetic neuropathy in rats. Diabetic rats showed a statistically significant reduction in H-wave-related sensory nerve conduction velocity (HSNCV) and in NGF content in sciatic nerves during the experiment of 8 weeks. No reduction in the CNTF content in sciatic nerves was seen in the diabetic rats. The epalrestat treatment, which started 4 weeks after STZ injection, resulted in a significantly greater NGF content and faster HSNCV than those in untreated diabetic rats. But no statistically significant alterations of motor nerve conduction velocity (MNCV) or CNTF content were seen during the treatment. ARI showed the stimulating effect for NGF synthesis/secretion in rat Schwann cell culture in vitro. These findings suggest that decreased levels of NGF in diabetic sciatic nerves may be involved in the pathogenesis of diabetic neuropathy in these rats and further show that epalrestat treatment can be useful for the treatment of diabetic neuropathy through NGF-induction in Schwann cells and/or inhibition of the polyol pathway.

Conservative treatment for cervical spondylotic myelopathy: achievement and sustainability of a level of "no disability".

We retrospectively reviewed 64 patients treated by the following methods: continuous head halter traction in bed (2 patients), cervical brace (19 patients), plaster bed holding head and trunk (15 patients), and Crutchfield's skull traction (28 patients), using the Japanese Orthopaedic Association grading system of motor function. A rate of "no disability" was achieved in 27% in the upper and 26% in the lower extremities. The achieved function was maintained in most patients, and some improved further during the follow-up period (3-10 years). The overall achievement rate was 34% in the upper and 28% in the lower extremities. Because the rate was significantly influenced by the degree of disability before treatment, the candidates are patients with mild disability for whom "no disability" is the goal.

The role of Gd-enhanced three-dimensional MRI fast low-angle shot (FLASH) in the evaluation of symptomatic lumbosacral nerve roots.

In the field of lumbar spine disorders, three-dimensional (3-D) magnetic resonance imaging (MRI) can clearly depict a lumbar nerve root from the distal region to the dorsal root ganglion. In this study, we used a gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced-three-dimensional (3-D) fast low-angle shot (FLASH) sequence when examining lumbosacral disorders. The subjects were 33 patients (14 men and 19 women) in whom lumbosacral neural compression had been diagnosed clinically. Twenty-one patients had lumbar disc herniation, 11 had lumbar spinal stenosis, and 1 had lumbar radiculopathy caused by rheumatoid arthritis. Five subjects with low back pain were also studied as a control group. In all patients and in all 5 of the controls, the dorsal root ganglion of every root was enhanced clearly. There was no root enhancement in the 5 controls. Enhancement of the symptomatic nerve roots, caused by compression, was found in 11 of the 33 patients. All 11 patients had radiculopathy, and muscle weakness was more frequent in patients with enhanced nerve roots than in those without enhancement. There was no enhancement of the cauda equina, even in the patients with cauda syndrome. The enhancement effect may reflect some pathological condition of the compressed nerve root and needs to be studied further.

Dopamine D4-like binding sites labeled by [3H]nemonapride include substantial serotonin 5-HT2A receptors in primate cerebral cortex.

Dopamine D4-like binding sites are abundant in human cerebral cortex as detected by [3H]nemonapride. The extremely low density of D4 mRNA in human cerebral cortex is inconsistent with the high amount of D4-like binding sites. To investigate the nature of the D4-like receptors, [3H]nemonapride binding sites in the nonhuman primate cerebral cortex were characterized. Although [3H]nemonapride binding sites were D4-like, displaceable by clozapine but not raclopride, [3H]nemonapride binding was not displaced by selective D4 antagonists but was displaced by the selective 5-HT2A antagonist MDL100907. Using [3H]ketanserin as a 5-HT2A ligand, nemonapride showed high affinity for monkey (Ki = 10.4 nM) and cloned human (Ki = 9.4 nM) 5-HT2A receptors, while its affinity for rat receptors was lower (Ki = 140 nM). The present study demonstrates that cerebral cortical D4-like binding sites labeled by [3H]nemonapride in nonhuman primates consist of a very small portion of D4, but a substantial portion of 5-HT2A receptors. The unexpectedly high affinity of nemonapride for primate 5-HT2A receptor suggests reconsidering previous data from other studies using [3H]nemonapride, particularly those on D4-like receptors.