A new family of heparin-binding growth/differentiation factors: increased midkine expression in Wilms' tumor and other human carcinomas

Midkine (MK) and heparin-binding growth-associated molecule/pleiotrophin form a new family of heparin-binding growth/differentiation factors. We studied MK gene expression in human tumors. In normal human reference tissues, MK was highly expressed in the mucosal tissue of the small intestine, moderately in the thyroid, weakly in the tissues of the lung, colon, stomach, kidney, and spleen, and not at all in the liver. All of 6 surgically removed specimens of Wilms' tumor highly expressed MK. Also, a moderate to intense level of MK expression was noted in the majority of surgically removed hepatocellular carcinomas. The MK mRNA level was analyzed in a number of cultured and nude mice-transplanted lines of human tumors. In stomach, colon, pancreatic, lung, and esophageal carcinomas, a moderate to high level of MK expression was found in the majority of them. These results suggest an important role of MK in the development and/or biological behavior of tumors and raised a possibility to use MK as a diagnostic marker. Heparin-binding growth associated molecule/pleiotrophin mRNA was low or scarcely detectable in samples analyzed thus far except for significant levels of the expression that were observed in PA-1 teratocarcinoma cells and in some surgical specimens of Wilms' tumor.     

Cloning, functional expression and tissue distribution of rabbit alpha 1d-adrenoceptor

We attempt to determine the utility of CERAD in detecting early Alzheimer's disease (AD). CERAD battery was administered to a group of 14 control subjects, 12 patients with possible dementia prodromes and to patients with Alzheimer's disease stratified according to severity (16 mild, 8 moderate). Other measures as some subtest of the Wechsler memory scale and the Rey Complex Figure Test were also applied. Delayed recall as well as logical memory of Wechsler memory scale were found to be the best discriminators for detecting very mild cases of AD (Prodromes) (p < 0.05). None of the memory test proved of value in staging the disorder. Visuospatial functions are better determinants of the progression of the illness. Fluency also distinguish between control subjects and very mild cases. These findings suggest that delayed recall memory and probably executive function are the most useful and sensitive indicators of Alzheimer's disease.     

Polymorphisms of dopamine receptor and transporter genes and Parkinson's disease

Disturbances of the dopamine system are involved in the pathogenesis of idiopathic Parkinson's disease (PD). Although genetic factors may play a role in the etiology of PD, there is little direct evidence implicating a specific gene. We conducted a study to test the hypothesis that allelic variations of the dopamine receptors (D2, D3, D4) and the dopamine transporter (DAT) contribute to the susceptibility to PD. Association analyses of 70 Japanese PD patients and the same number of age-matched controls did not reveal any association between alleles of the D2, D3 or D4 receptor genes or the DAT gene and PD. Thus, our results suggest that factor(s) other than allelic variations of these key proteins in the dopamine system contribute to the susceptibility to PD.     

SO(3) nonlinear σ model for a spiral phase in the spin-fermion model

Starting from a doped spin-fermion model for the CuO₂ planes in high-T_c superconductors, we derive an effective continuum theory for the spin degrees of freedom by means of a gradient expansion. We assume an incommmensurate, spiral configuration for the spins. Extending our previous treatment of a planar spiral, we allow for three-dimensional fluctuations of the spin fields, which are described by an S0(3) matrix order parameter. The continuum limit is obtained by a systematic expansion in powers of a short distance cutoff. The occurring infinite series is summed to all orders using a combinatorial method which exploits the constraint obeyed by the S0(3) order parameter. The resulting continuum theory is given by an S0(3) quantum nonlinear model, where the influence of doping is contained in the fermionic susceptibilities that enter into the coupling constants of the model.     

The cluster of arachnoid diverticula in the occipital bone: report of two cases with literature review

The authors report two cases of multicentric osteolytic lesions in the occipital bone without any history of head trauma. The excisional biopsy of the first case revealed that the lesion was multicentric but a continuous cavity with the subarachnoid space through various sizes of dural defect, and the cavities were covered by arachnoid lining. Together with the previously reported similar 5 cases, the characteristic common feature is multicentric osteolytic lesions in the occipital bone at advanced age without marginal sclerosis. "The cluster of arachnoid diverticula in the occipital bone (CADOB)" is probably the most appropriate term for these non-traumatic lesions with the following characteristics: elderly patients, occipital bone, midline, multiple, intact outer table, nonsclerotic margin and without history of trauma. Operation may not be indicated because of its non-progressive and benign nature.     

Peptide and protein mimetics inhibiting amyloid beta-peptide aggregation

Protein misfolding is related to some fatal diseases including Alzheimer's disease (AD). Amyloid beta-peptide (Abeta) generated from amyloid precursor protein can aggregate into amyloid fibrils, which are known to be a major component of Abeta deposits (senile plaques). The fibril formation of Abeta is typical of a nucleation-dependent process through self-recognition. Moreover, during fibrillization, several metastable intermediates such as soluble oligomers, including Abeta-derived diffusible ligands (ADDLs) and Abeta*56, are produced, which are thought to be the most toxic species to neuronal cells. Therefore, construction of molecules that decrease the Abeta aggregates, including soluble oligomers, protofibrils, and amyloid fibrils, might further our understanding of the mechanism(s) behind fibril formation and enable targeted drug discovery against AD. To this aim, various peptides and peptide derivatives have been constructed using the "Abeta binding element" based on the structural models of Abeta amyloid fibrils and the mechanisms of self-assembly. The central hydrophobic amino acid sequence, LVFF, of Abeta is a key sequence to self-assemble into amyloid fibrils. By combination of this core sequence with a hydrophobic or hydrophilic moiety, such as cholic acid or aminoethoxy ethoxy acetic acid units, respectively, good inhibitors of Abeta aggregation can be designed and synthesized. A peptide, LF, consisting of the sequence Ac-KQKLLLFLEE-NH 2, was designed based on the core sequence of Abeta but with a simplified amino acid sequence. The LF peptide can form amyloid-like fibrils that efficiently coassemble with mature Abeta1-42 fibrils. The LF peptide was also observed to immediately transform the soluble oligomers of Abeta1-42, which are thought to pose toxicity in AD, into amyloid-like fibrils. On the other hand, two Abeta-like beta-strands with a parallel orientation were embedded in green fluorescent protein (GFP), comprised of a beta-barrel structure, to make pseudo-Abeta beta-sheets on its surface. The GFP variant P13H binds to Abeta1-42 and inhibits Abeta1-42 oligomerization effectively in a substoichiometric condition. Thus, molecules capable of binding to Abeta can be designed based on structural similarities with the Abeta molecule. The peptide and protein mimetics based on the structural features of Abeta might lead to the development of drug candidates against AD.     

Occurrence and sources of perfluorinated surfactants in rivers in Japan

We analyzed perfluorinated surfactants (PFSs) in 20 river samples and 5 wastewater secondary effluent samples in Japan to reveal their occurrence and sources. Nine PFS species were determined: perfluorooctanesulfonate (PFOS), perfluorooctane sulfonamide (FOSA), perfluoroheptanoate (PFHpA), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUA), perfluorododecanoate (PFDDA), and perfluorotridecanoate (PFTDA). PFSs were detected in all rivers, revealing nationwide contamination of rivers. In particular, 11 out of 20 river samples exceeded New Jersey guidance for PFOA in drinking water (40 ng/L). PFOS, PFHpA, PFOA, and PFNA were major species in Japan. Concentrations of PFOS, PFHpA, and PFNA in rivers were strongly correlated with population density, suggesting that the chemicals were derived from urban activities. PFOA showed a significant but weak correlation. We used crotamiton, a marker of sewage effluent, for further source analysis. Concentrations of PFOS, PFHpA, and PFNAwere strongly correlated with those of crotamiton, and plots of secondary effluents fell near the regression lines of rivers, indicating that the PFOS, PFHpA, and PFNA in rivers were derived from sewage effluent. On the other hand, PFOA was found at remarkably high levels (54-192 ng/L) in seven river samples containing low levels of crotamiton, suggesting that it was derived from nonsewage point sources, as well as sewage effluent. The total fluxes of sewage-derived PFOS, PFHpA, PFOA, and PFNA from Japan were estimated to be 3.6, 2.6, 5.6, and 2.6 t/year, respectively. This is the first report to identify PFOA in several rivers, derived from nonsewage point sources, by using a marker of sewage effluent.     

High-Performance Induction Motor Drive System Using a PWM Inverter

A high-performance speed control system for cage induction motors is described which utilizes a PWM inverter. The effects of primary current coincidence and machine constant variation on system characteristics such as response time, torque precision, and operating noise were investigated. Based on the results obtained, new control methods have been devised; one varies the gain of the current controller in proportion to the primary frequency, and a second compensates for the slip frequency by using the deviation between the flux reference value and the actual value. Effectiveness of the compensation methods was confirmed in tests.