A new method for the synthesis of polymers containing amide and imide groups in the main chain

Poly(pyromellitdiimidoarylenecarbonyliminoaryleneiminocarbonylarylene)s [poly(amide-imide)s] ( 7 and 12 ) were prepared from pyromellitic dianhydride ( 6 ) and dicarbamates ( 5 ) (diurethanes) containing amide linkages. The same polymers could also be prepared directly from aromatic isocyanatocarboxylic acid chlorides ( 10 ), diamines ( 11 ) and 6 . In the latter method, the addition of an equimolar amount of water was required for the formation of the imide ring in the main chain of the polymer. Model reactions were carried out to determine the reaction conditions for the two methods. Reaction mechanisms are proposed.     

Development of a safe oral Abeta vaccine using recombinant adeno-associated virus vector for Alzheimer's disease

A new oral vaccine for Alzheimer's disease was developed using recombinant adeno-associated virus vector carrying Abeta cDNA (AAV/Abeta). Oral administration of the vaccine without adjuvant induced the expression and secretion of Abeta1-43 or Abeta1-21 in the epithelial cell layer of the intestine in amyloid precursor protein transgenic mice. Serum antibody levels were elevated for more than six months, while T cell proliferative responses to Abeta was not detected. Brain Abeta burden was significantly decreased compared to the control without inflammatory changes. This oral AAV/Abeta vaccine seems to be promising for prevention and treatment of Alzheimer's disease.     

Study of the familiar form of vascular dementia (CADASIL)]

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an inherited disease characterized by recurrent subcortical ischemic strokes leading to pseudobulbar palsy, migraine attacks with aura, psychiatric disturbances and vascular dementia. The disease is caused by mutations in the Notch3 receptor. In the present study, we investigated the mechanisms underlying the pathological alterations in CADASIL. We found no difference in the receptor trafficking, processing, or specificity for ligand binding or signal transduction between WT and mutant Notch3 receptors. These results suggest that pathological alterations in CADASIL are not caused by defects in Notch3 processing or signaling.     

Extravasation of contrast medium into the gastrointestinal tract following lymphangiography: Report of two cases

Two cases with roentgenologic findings of extravasation of contrast medium into the stomach and colon following lymphangiography are presented. One is clinically diagnosed as primary intestinal lymphangiectasia; the other as retroperitoneal spread from uterine cancer. The significance of lymphangiography in gastrointestinal or retroperitoneal disorders is discussed.     

Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice

Some lines of evidence have suggested that subcortical ischemic vascular dementia (SIVD) is a common form of vascular dementia (VaD), and that its pathological changes are the development of ischemic white matter (WM) lesions under chronic hypoperfusion and lacunes. Here, we have developed a novel mouse model of VaD with WM lesions, which was induced by right unilateral common carotid artery occlusion (rUCCAO). The mice subjected to rUCCAO exhibited chronic cerebral hypoperfusion in the cerebral hemisphere ipsilateral to rUCCAO monitored using a laser-Doppler flow meter (p<0.01), and significant WM damage in the corpus callosum (p<0.05) and deficits in object recognition test correlated with the damage of frontal-subcortical circuits (p<0.01). However, no differences in spontaneous alternation or spontaneous motor activity were observed. Furthermore, the levels of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), significantly increased (p<0.01), and those of anti-inflammatory cytokines, such as interleukin-4 (IL-4) and interleukin-10 (IL-10), significantly decreased in the ischemic brain (p<0.05). These results suggest that this model is a useful tool for investigating the associations among inflammatory reactions, cognitive impairment, and WM damage, which may help elucidating the pathomechanism of VaD, particularly SIVD.     

Synthesis of aromatic polyamides from isocyanatocarboxylic acid chlorides and dimethylsulfoxide or water

Aromatic isocyanatocarboxylic acid chlorides ( 1a–i ) reacted with stoichiometrical quantities of dimethyl sulfoxide in ether to yield poly(N-carboxyanhydride)s ( 5 ) which were converted into polyamides ( 6 ) by heating them at elevated temperatures. Isocyanatocarboxylic acid chlorides also reacted with water to produce polyamides 6 . The reaction paths were followed by quantitative analysis of carbon dioxide evolved, by measurement of IR spectra, and by thermal analysis of the polymers.     

A case of early stage CADASIL showing only dizziness and vertigo with a novel mutation of Notch 3 gene]

We report a 39-year-old woman who presented with only dizziness and vertigo for 2 months. Neurological examination revealed no abnormalities except for hypereflexia on the left side extremities. Neurootological examination revealed no abnormalities. MRI of the brain demonstrated patchy hyperintensity areas on FLAIR images in the periventricular white matter and external capsule. Her grandmother had cerebral infarction and her father is suffering from multi-infarct dementia. Her second older sister who similarly had dizziness and vertigo demonstrated similar MRI findings characterized by patchy hyperintensity areas in the white matter and external capsule even though she had no risk factors for atherosclerosis. Her third older sister also had dizziness and vertigo and had patchy hyperintensity areas in the white matter in her brain MRI even though she had no risk factors for atherosclerosis. Based on this family history, we suspected that she had cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Mutational analysis of Notch3 gene disclosed a novel missense mutation substituting arginine for cysteine at codon 206 (C206R) in exon 4 of the Notch3 gene, confirming the diagnosis of CADASIL. Interestingly, similar dizziness and vertigo were present not only in the patient, but also in the other two sisters who had the same gene mutation as the patient. This report supports the idea that the external capsule lesion is one of the signs suggestive of CADASIL as a diagnosis.     

Genetic,clinical and pathological studies of CADASIL in Japan: a partial contribution of Notch3 mutations and implications of smooth muscle cell degeneration for the pathogenesis

We have examined Notch3 mutations in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) whose samples were submitted to us in Japan. The subjects were composed of 21 Japanese, 1 Iranian, 1 Korean and 1 Canadian families. Mutations in the Notch3 gene were found in 7 of 24 families examined. These were R133C in two unrelated Japanese families, and R213K, C174F and R169C in each Japanese family. In addition, we have found R90C in an Iranian family and C174R in a Korean family. Thus, contribution of Notch3 gene mutations is less than one fourth of Japanese CADASIL families, suggesting the existence of other causative genes in CADASIL. It is also of interest to know that Notch3 mutant CADASIL exists in other Asian countries.We next examined the localization of Notch3 protein in the tissue by immunohistochemistry. It was restricted to the wall of arterioles in the brain and other organs. In the brain, there was no difference in the staining pattern among arterioles in the cortex, white matter and meninges. The staining was negative in the venule and capillaries as well as in neurons and glial cells. From the staining pattern, it was recognized to be expressed in the vascular smooth muscle cells in the adult tissue. In an autopsy case with R213K mutation, we could see numerous cerebral infarcts and arteriole wall degeneration with deposits of granular osmiophilic material (GOM). However, it is interesting to note that occlusion of arterioles was rarely observed and the GOM was negative for Notch3 staining. These findings suggest that hemodynamic abnormalities due to smooth muscle cell degeneration may be important in the pathogenesis of CADASIL.