Evidence for a glycosaminoglycan on the nudel protein important for dorsoventral patterning of the drosophila embryo.

Dorsoventral patterning of the Drosophila embryo requires Nudel, a large mosaic protein with a protease domain. Previous studies have implicated Nudel's protease domain as the trigger of a proteolytic cascade that activates the Toll signaling pathway to establish dorsoventral polarity in the embryo. However, the function of other regions of Nudel has been unclear. By using two-dimensional gel electrophoresis and site-directed mutagenesis, we have obtained evidence that the N-terminal region of Nudel contains a site for glycosaminoglycan (GAG) attachment that is required for dorsoventral patterning. Disruption of this site blocks a disulfide-based association between N- and C-terminal Nudel polypeptides and proteolytic activation of Nudel's protease domain. We discuss how a GAG chain on Nudel might be required for Nudel protease activation.     

Simulation for population analysis of Michaelis-Menten elimination kinetics

A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE) requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method, ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological half-life of a drug. This work was supported in part by the Epilepsy Research Foundation, the Nakatomi Foundation, and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.     

Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.     

Development of the brainstem: assessment by MR imaging

The morphological development of the brainstem was studied by means of MR imaging. The subjects were 74 cases ranging in age from 4 months to 16 years, and 6 adult cases. The brainstem development was rapid until 4-6 years of age and thereafter it slowed down. That is the brainstem showed exponential growth (w', t', v and u). The relationship between brainstem growth and the cranium size was divided into 4 types as follows: 1) linear increase with development (s/T-O), 2) plateau (w/T-I and v/RTP-LTP), 3) down and up (u/RTM-LTM and z/RTM-LTM) and 4) exponential (t/T-P). In the values of v, z (the size of the brainstem in axial view) and t/T-P (the ratio of the midbrain and the cranium size in sagittal view), there were significant sex differences for cases of 10-16 years old. These values in male subjects were greater than those in female subjects (v, p less than 0.05, z, p less than 0.01, and t/T-P, p less than 0.05). That is the brainstem in male subjects was greater than that in female subjects.     

Autoperfusion balloon catheter for treatment of vertebral artery stenosis

Percutaneous transluminal angioplasty (PTA) of the vertebral artery was performed with an autoperfusion balloon catheter in five patients. There were no complications in the form of embolic episodes or neurological deficits due to brain ischaemia during inflation. In critical cases with insufficient collateral circulation during temporary occlusion, the use of an autoperfusion balloon catheter may expand the indications for PTA in patients with ischaemic cerebrovascular disease.     

MR imaging of intraspinal tumors—Capability in histological differentiation and compartmentalization of extramedullary tumors

Summary Magnetic resonance (MR) images of 29 consecutive patients with intraspinal neoplasms (9 intramedullary tumors, 20 extramedullary tumors) were reviewed to evaluated the utility of MR imaging in distinguishing the intraspinal compartmental localisation and signal characteristics of each lesion. Compartment and histology of all neoplasms were surgically proven. MR correctly assigned one of three compartments to all lesions, 9 intramedullary, 14 intradural extramedullary (6 schwannomas, 3 neurofibromas, 5 meningiomas), and 6 extradural (3 schwannomas, 1 meningioma, 1 cavernous hemangioma, 1 metastatic renal cell carcinoma). All intramedullary tumors showed swelling of the spinal cord itself. In all five extradural tumors a low intensity band was visualized between the spinal cord and tumor. On the other hand, a low intensity band was demonstrated in no cases with intradural tumors. Visualization of this low intensity band is important in differentiating extradural from intradural-extramedullary lesions. We call this low intensity band, the extradural sign. Signal intensity of intradural tumors varied with histology. In extramedullary tumors, signal intensity of schwannomas was similar to that of the cerebrospinal fluid (CSF) both on T1 weighted (inversion recovery) and T2 weighted spin echo (SE) images. On the other hand, meningiomas tended to be isointense to the spinal cord on both T1 and T2 weighted SE images. We found relatively reliable signal characteristics to discriminate meningioma from schwannoma.     

MR imaging of dural arteriovenous malformations with ocular signs

Summary Four patients with dural arteriovenous malformation (AVMs) draining into the cavernous sinus, who presented ophthalmic manifestations, were studied by magnetic resonance (MR) imaging. In all patients signal decrease in the involved cavernous sinus was demonstrated in coronal spinecho (SE) imaging. It is attributable to rapid venous flow in the sinus, and this high velocity signal loss is a fairly pathognomonic finding in this condition. We stress the validity of MR imaging in the primary diagnosis of dural AVMs with ophthalmic symptoms.