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Quantitative structure-activity relationship (QSAR) analysis is a practical approach by which chemical structure is quantitatively correlated with biological activity or chemical reactivity. Human ABC transporter ABCG2 exhibits broad substrate specificity toward structurally diverse compounds. To gain insight into the relationship between the molecular structures of compounds and the interaction with ABCG2, we have developed an algorithm that analyzes QSAR to evaluate ABCG2-drug interactions. In addition, to support QSAR analysis, we developed a high-speed screening method for analyzing the drug-drug interactions of ABCG2. Based on both experimental results and computational QSAR analysis data, we propose a hypothetical mechanism underlying ABC-mediated drug transport and its interaction with drugs.

A versatile soft x-ray flat-field grating spectrograph to be installed to a conventional transmission electron microscope has been developed. A holographic spherical grating of a 1200-lines/mm effective groove density which places emphasis on the low energy region of 50-200 eV is designed by an aspheric wavefront recording system. Laminar and blazed types master (LM and BM) gratings and their respective replica (LR and BR) gratings are fabricated by holographic exposure and ion-beam etching methods. Absolute diffraction efficiencies in the 50-300 eV range at the angle of incidence of 86.0 degrees were measured using a synchrotron radiation. The first order diffraction efficiencies are 6.1-7.5% (or 12%) for LM (or BM) and 7.4-9.6% (or 13%) for LR (or BR) gratings at near 55 eV, and over 5% (or 8%) in the 50-200 eV range for LM and LR (or BM and BR) gratings. The replica gratings show the comparable first-order diffraction efficiencies with their respective laminar and blazed types of master gratings.

Extracranial vertebral artery aneurysm associated with neurofibromatosis (NF1) is very rare. The aneurysm was successfully treated by endovascular trapping of the aneurysm and proximal vertebral artery with coils.

The Japanese quarantine system monitors incoming passengers to detect imported pathogens at international airports. At one airport, we found that 74% of 13315 travellers returning with diarrhoea had visited only one country before entering Japan. On the basis of our results, we hypothesized that the international distribution and potential source of bacterial strains could be inferred by analysing strains isolated from travellers returning to Japan. In order to demonstrate the potential for this system, we randomly selected five Shigella sonnei strains and examined their restriction fragment length polymorphism patterns. One set of strains appeared to be closely related, while three sets, isolated from travellers who visited different countries were possibly related. These results suggest that international distributions and potential sources of S. sonnei may be inferred by monitoring isolates from passengers arriving at a Japanese quarantine station.

Numerous peptide aptamers that recognize inorganic materials have been isolated using in vitro peptide evolution systems. However, it remains unknown how peptides interact with inorganic materials or how specific those interactions are. We, therefore, assessed the target specificities of the peptide aptamer TBP-1 (RKLPDAPGMHTW) by monitoring its ability to bind 10 different metals. We found that phages displaying TBP-1 bound to Ti, Si, and Ag surfaces but not to Au, Cr, Pt, Sn, Zn, Cu, or Fe. As previously seen with Ti, binding to Si and Ag was diminished by R1A, P4A, or D5A mutation, suggesting that the same molecular mechanism underlies TBP-1 binding to all three materials. We also observed that a synthetic TBP-1 peptide mediated mineralization of both silica and Ag. It, thus, appears that although the overall chemical characteristics of Ti, Si, and Ag surfaces are dissimilar, they share a common subnanometric structure that is recognized by TBP-1.

Purpose. To study operative treatment and postoperative clinical outcomes of hip fracture in haemodialysed patients.Methods. In 12 patients (8 men and 4 women) undergoing haemodialysis, 14 hip fractures were treated. Of these, 8 hips were treated with bipolar hip arthroplasty, one hip with total hip arthroplasty, 4 hips with a compression hip screw, and one hip with a gamma nail. The mean duration of dialysis treatment until fracture was 7 years. During a mean postoperative follow-up period of 17 months (range, 1–44 months), the patients' renal condition, type of fracture, and level of activities of daily living before and after surgery were assessed.Results. Of the 7 patients who died during a mean follow-up period of 17 months, 2 died from myocardial infarction, 2 from sepsis, and one each from gastric cancer, pulmonary oedema, and liver failure. Five of the 8 patients with diabetic nephropathy died, whereas 6 of the 8 patients who underwent bipolar hip arthroplasty or total hip arthroplasty died. Most of the patients had declined level of activities of daily living postoperatively.Conclusion. For haemodialysed patients with fractures, it is essential to select the most suitable operating method and to conduct vigilant management before and after the operation.

Background and objectives: We have previously reported that recombinant γ275Cys fibrinogen exhibits a marked impairment of functions as well as aberrant fibrin clot and bundle structures, as compared with wild‐type, γ275Arg, and plasma fibrinogen from a heterozygous proband. Since γArg275His mutations have also been reported in 10 families, we synthesized recombinant γ275His fibrinogen and γ275Ala fibrinogen (as a control) and analyzed and compared them with γ275Cys and γ275Arg. Methods: A variant γ‐chain expression plasmid was transfected into Chinese hamster ovary cells expressing normal human fibrinogen Aα‐ and Bβ‐chains. After purification of the recombinant variant fibrinogens, we performed functional analyzes for thrombin‐catalyzed fibrin polymerization and factor XIIIa (FXIIIa)‐catalyzed γ‐γ dimer formation from fibrin or fibrinogen and also ultrastructural analysis of fibrin clots and bundles. Results: By comparison with both γ275His and γ275Ala fibrinogens, recombinant γ275Cys fibrinogen exhibited a more impaired γ‐γ dimer formation from fibrin or fibrinogen, a more aberrant fibrin clot structure, and thicker fibers in fibrin bundles. In 1 : 1 mixtures of γ275Arg and γ275Cys fibrinogens or γ275Arg and γ275His fibrinogens, thrombin‐catalyzed fibrin polymerization and both fibrin clot and fiber structures showed some compensation (as compared with γ275Cys or γ275His alone). Conclusion: These results strongly suggest that an amino acid substitution of γ275Arg alone disrupts D:D interactions in thrombin‐catalyzed fibrin polymerization and the formation of fibrin bundles and fibrin clots. Moreover, the existence of a subsequent disulfide‐linked Cys in γ275C fibrinogen augments the impairment caused by a His or Ala substitution.

The survey of Vibrio cholerae O1 in marine area was carried out in the Port of Osaka, Japan in 1987–2001, and 51 V. cholerae O1 strains were isolated. All strains were identified to be of El Tor biotype, Ogawa serotype and classic Ubon Kappa-phage type, and were cholera toxin (CT)-negative and CT gene-negative. In order to clarify certain ecological aspects of V. cholerae O1 in the marine environment of the temperate zone, we performed molecular analysis of the isolated strains using pulsed-field gel electrophoresis (PFGE) with NotI and SfiI restriction enzymes. We found the indistinguishable strains by DNA analysis using PFGE with strains passed for 1 year, and also found the closely related strains with that passed for 3 and 12 years. Those results indicated that V. cholerae O1 can survive over one winter at least, and that it survives in marine water for a long time by undergoing continuous mutation.

A novel compositional accommodation mechanism in perovskite (ABO3) SrNbO3thin films was revealed by field‐emission analytical electron microscopy (AEM). A new analytical methodology for estimating localized structures such as planar faults is also presented. The method was applied for investigating the compositional accommodation mechanism of B‐ion‐rich SrNbO3epitaxial thin films. Two types of accommodation mechanism—formation of B‐ion‐rich amorphous phase and (110)‐located high‐density planar defects—were revealed. The latter mechanism is a new finding for B‐ion‐rich perovskites. Copyright © 2003 John Wiley & Sons, Ltd.

A novel compositional accommodation mechanism in perovskite (ABO3) SrNbO3 thin films was revealed by field-emission analytical electron microscopy (AEM). A new analytical methodology for estimating localized structures such as planar faults is also presented. The method was applied for investigating the compositional accommodation mechanism of B-ion-rich SrNbO3 epitaxial thin films. Two types of accommodation mechanism—formation of B-ion-rich amorphous phase and (110)-located high-density planar defects—were revealed. The latter mechanism is a new finding for B-ion-rich perovskites. Copyright © 2003 John Wiley & Sons, Ltd.

Pf-gp6, a 6 kDa anti-degranulation glycoprotein purified from the extract of Perilla frutescens, was examined for its antiviral activity against HIV-1 and HIV-2 in vitro. HIV-1-induced cytopathic effect and proviral DNA synthesis were inhibited in the presence of Pf-gp6. The 50% inhibitory concentrations of Pf-gp6 for various HIV-1 strains, including clinical isolates and CCR5-using (R5) HIV-1, ranged between 1.3 and 71.0 μg/ml, depending on the combination of viral strain and host cell. Furthermore, Pf-gp6 did not directly inactivate infectious viral particles. A time-of-addition experiment revealed that Pf-gp6 lost its activity before zidovudine but after the CXCR-4 antagonist AMD3100 during the early stage of viral infection. Although the pinpoint target of Pf-gp6 remains to be elucidated, it may interfere with a step between viral entry and reverse transcription.

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Abstract:: Current-voltage (J-V) and differential-conductivity-voltage ( dJ/dV-V) characteristics are analytically calculated at zero temperature for a point contact consisting of: two Peierls conductors P  ( = 1, 2) separated by an insulator (I). Here P is a conductor with charge density wave (CDW). The J-V and dJ/dV-V characteristics depend on the CDW phases  ( = 1, 2) in the mean field approximation. To calculate them analytically we assumed, = ≡Δ where  ( = 1, 2) are the energy gaps of P  ( = 1, 2). The current J has a discontinuous jump at eV = 2Δ for ϕ1 = ϕ2≠ 0. The differential conductivity dJ/dV has a singularity at eV = 2Δ for ϕ1 = ϕ2≠ 0. The relation J(V,ϕ1,ϕ2) = - J(- V,ϕ1 + π,ϕ2 + π) is obtained.

Monte Carlo simulations were performed to study the defect formation in ZnSe/GaAs heterovalent epitaxy. It was shown that when ZnSe is grown on the GaAs (001) As-rich c(4 × 4) surface, As antisites become the origin of defects such as dislocations, while ZnSe grows in a step-flow manner on the GaAs (110) (1 × 2) surface without any sign of defect production. These results originate from the heterovalency between ZnSe and GaAs and well explain the observations.

Surface chemistry of the capacity fading of the LixMn2O4 cathode was investigated using atomic force microscopy (AFM), energy-dispersive X-ray analysis (EDAX), and X-ray photoelectron spectroscopy (XPS). Measurements show a decrease in the cathode capacity from 124 mA h g^-1 before storage to 102 mA h g^-1 after storage in an electrolyte of 1 M LiPF6/EC + DMC + DEC at 70 °C for 5 days. Surface morphological changes of the LixMn2O4 cathode were monitored using contact and tapping AFM and lateral force microscopy in air. Nanoscale changes of the charged cathode before and after storage at 70 °C were observed. Before storage, homogeneous grains of approximately 100−200 nm are seen. After storage, fine and nearly round shaped structures of 10−30 nm in size are observed covering the larger grains on the surface of the cathode. This change in morphology suggests film deposition on the cathode's surface, which increases the resistance for Li⁺ ion transport in and out of the cathode. Results from EDAX show that compounds containing phosphorus and fluorine are also deposited on the surface of the cathode. Surface analysis of the cathode with XPS suggests the presence of MnF2. The conversion of the oxidation state of manganese on the surface of the cathode from MnO2 to MnO during storage at the elevated temperature was observed with XPS.

Abstract We describe a case of reversible hepatofugal portal flow 1 week after transplantation of a small‐for‐size liver graft from a living donor. A transient increase in intrahepatic portal vascular resistance was the suspected cause. The portal venous flow normalized after residual collateral channels had been interrupted surgically. The patient was discharged on the 90thpostoperative day. Liver transplant clinicians should be aware that hepatofugal flow can occur with small‐for‐size liver grafts, despite sufficient portal venous flow immediately after transplantation.

The membrane filter technique for smear specimens of tumors in bromodeoxyuridine (BrdU) immunochemistry is described. The staining results of Raji cells processed using the filter technique was compared with that obtained by the conventional cytospin method. Although the BrdU mean labeling index (LI) for in cytospin specimens was almost the same as the LI in membrane filter specimens, filter specimens showed excellent staining and less cell destruction compared with those processed by cytospin. Small amounts of tumor specimens such as squamous cell carcinoma and polymorphous low-grade adenocarcinoma also were processed using the membrane filter appliance. For squamous cell carcinoma, the LI for the filter specimens was 5.36 ± 0.38 and that of the paraffin sections was 5.56 ± 0.38. The membrane filter technique provided relatively undamaged specimens for exfoliative cytology and will be useful for immunohistochemical evaluation of tumor cells and for routine, noninvasive cytological screening.

Human chromosomes 1q21-q25, 6p21.3-22.2, 9q33-q34, and 19p13.1-p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21-25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21-q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides.

Shiga toxin-producing Escherichia coli (STEC) O157 was investigated with respect to its halotolerance and whether it can survive in marine water. STEC O157 could multiply in a medium containing 5% NaCl and in sterilized marine water, and could survive in unsterilized marine water for at least 15 days. On the basis of these results, we postulated that STEC O157 may survive in natural marine water, and attempted to isolate the bacterium and Shiga toxin gene (stx) from marine water in Japan. The stx, comprising stx1 and stx2, was detected from marine water samples by PCR. STEC and other stx-positive bacteria, however, could not be isolated from these samples in this study. These results indicate that stx-positive bacteria may survive in marine water and suggest the necessity of a survey.

Electron microscopic in situ hybridization (EM-ISH) is a useful method in determining the localization of a specific nucleic acid at the ultrastructural level. Since the EM-ISH protocol includes many steps, no standard protocol for EM-ISH is available yet. In this study, we optimized quantitatively the critical conditions with respect to embedding resin, nucleic acid labeling and hybridization reaction time, by using adenovirus-infected cells as the indicator cells. The optimal detection of an adenovirus-specific nucleic acid was obtained by overnight hybridization reaction on sections embedded in Lowicryl K4M resin. Random-primed-labeled probes improved the reactivity. At least 60% of virus particles in paracrystalline arrays was found to contain viral DNA. These arrays in adenovirus-infected cells are useful in evaluating quantitatively the efficiency of protocols of EM-ISH.

We performed positron emission tomography (PET) with 18fluorine-fluoro-2-deoxy-D-glucose (FDG) on 55 patients with tumours involving the musculoskeletal system in order to evaluate its role in operative planning. The standardised uptake value (SUV) of FDG was calculated and, to distinguish malignancies from benign lesions, the cases were divided into high (= 1.9) and low (< 1.9) SUV groups.The sensitivity of PET for correctly diagnosing malignancy was 100% with a specificity of 76.9% and an overall accuracy of 83.0%. The mean SUV for metastatic lesions was twice that for primary sarcomas (p < 0.0015).Our results suggest that the SUV may be useful in differentiating malignant tumours from benign lesions. However, some of the latter, such as schwannomas, had high SUVs so that biopsy or wide resection was selected as the first operation. Thus, some other quantitative analysis may be required for preoperative planning in cases of high-SUV neurogenic benign tumours. The reverse transcription-polymerase chain reaction revealed that the RNA message of a key enzyme in glucose metabolism, phosphohexose isomerase (PHI)/autocrine motility factor, was augmented in only high FDG-uptake lesions, suggesting that a high expression of the PHI message may be associated with accumulation of FDG in musculoskeletal tumours.

ObjectiveThe surgical outcome of idiopathic tarsal tunnel syndrome (TTS) is reported to be worse than that attributable to ganglion, tarsal coalition, or tumour, and therefore further development in the surgical treatment for idiopathic TTS is considered to be necessary. Here the efficacy of neurovascular decompression for patients with idiopathic TTS is evaluated.MethodsTwelve feet from nine patients with idiopathic TTS were treated. The patients were aged 52-78 years (mean 64.6 years), and all of them complained of pain or dysaesthesia of the sole of the foot. The posterior tibial nerve was freed from the attached arteriovenous complex (posterior tibial artery and veins). The dissected nerve had a flattened appearance in all of the patients, suggesting nerve compression by the adjacent arteriovenous complex and superficially by the flexor retinaculum. A graft of fat was inserted as both a cushion and an antiadhesive between the vessels and the nerve to achieve neurovascular decompression.ResultsPatients on whom neurovascular decompression was performed had resolution or lessening of symptoms in their feet. Neither wound infection nor recurrence of symptoms was found during the follow up period (mean 26.8 months).ConclusionNeurovascular compression syndrome plays a part in idiopathic TTS, and adding neurovascular decompression to resection of the flexor retinaculum is effective.

The remote plasma enhanced chemical vapor depositions (RPECVD) using organo-silicon as source compounds have been examined in terms of the mechanism of the activation steps and film formation. The deposition experiments were performed for different configurations of the radical transportation tube (straight, with a light trap, and a radical trap) to prove how the source materials are effective for the film formation. In the SiC film formation, it is shown that hydrogen radicals act on the SiSi bonds or SiH bonds of the source materials, but SiC bonds in the source will not be broken by the hydrogen radicals because of its high binding energy. As a practical application, SiC film coatings on the plastic are examined using electron cyclotron resonance (ECR) plasma system. These SiC coatings provide many advantages for the development of scratch resistivity and UV degradation resistivity for plastic materials.

Abstract: Background. Although uranyl acetate (UA) is known to induce apoptosis in renal tubular cells, the pathophysiological role of apoptotic cell death in UA-induced acute renal failure (ARF) is not clear. In this study, we examined whether glycine, which is known to provide protection against nephrotoxic acute renal failure, attenuated tubular damage in UA-induced ARF in rats, and, if so, whether the attenuation of tubular damage was associated with reduced apoptotic cell death. Methods. Sprague-Dawley rats were allocated to three groups; normal controls, UA-treated, and UA plus glycine-treated. Acute renal failure was induced by the intravenous injection of UA (5 mg/kg). UA plus glycine-treated rats were given glycine at 1 g/kg, i.v. over 3 min at the same time as the UA injection. Serum creatinine concentration (Scr) and tubular damage score were examined 5 days after UA administration. Apoptosis was evaluated by counting the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in the outer stripe of the outer medulla. Results. Glycine significantly decreased the UA-induced increases in Scr (3.73 � 0.31 vs 2.74 � 0.11 mg/dl; P < 0.05) and the tubular damage score (3.83 � 0.13 vs 2.58 � 0.01; P < 0.01). UA significantly increased the number of TUNEL-positive cells in the outer stripe of the outer medulla (0.16 � 0.04 vs 7.45 � 0.46/high power field at �400 magnification; P < 0.01 vs normal control value). Glycine infusion significantly lessened the number of TUNEL-positive cells (5.84 � 0.31/ high power field at �400 magnification; P < 0.01 vs UA-treated rats). A significant correlation was found between the number of TUNEL-positive cells and the tubular damage score (r = 0.93; P < 0.01). Conclusion. Glycine ameliorated the severity of UA-induced ARF and the degree of apoptotic cell death. This finding suggested that the protective effect of glycine in UA-induced ARF may be mediated, at least in part, through a reduction of apoptosis.

Sciatic nerves were excised from 3 beagle dogs about 5 h after their sacrifice, treated three times by freezing and thawing, and stored in physiological saline for 3 months at −20°C until used. Nerve segments 5 cm in length prepared from these stored nerves were transplanted to the common peroneal nerve in the right hindlimb of beagle dogs. Sixteen beagle dogs in total were used, in four treatment groups of two pairs each studied at 1 and 3 months. Five-hundred microliters basic fibroblast growth factor (bFGF) of two different concentrations (10 μg/300 μl and 100 μg/300 μl) which were impregnated in 0.5 ml gelatin hydrogels was applied around the sutured allografts. Autografting was also done in 4 beagle dogs, with no bFGF application. One month after the grafting, no regenerating nerves extended beyond the middle of the transplant in any of the allografts, except in the autografts in which a number of regenerated (myelinated) axons were present. Three months after the grafting, an abundance of myelinated axons was found at the middle of the graft: the numbers of axons per 104μm2were 22.6 in the autografts and 10.6, 10.4 and 19.2 in the allografts treated with no bFGF, low-dose bFGF, and high-dose bFGF, respectively. Regenerating axons extended into the host nerve: the numbers of myelinated axons at the level 1.5 cm distal to the distal suture were 35.7, 0.9, 3.8, and 12.1 per 104μm2in the above respective order. Although it was inferior in quality to the autograft, peripheral nerve regeneration was extensive in the distal nerve using freeze–thawed and bFGF-treated allografts at 3 months. Electromyography showed that the peroneus longus muscle responded to the electrical stimuli given at the site proximal to the transplant in all four groups. These data indicate that a 5-cm acellular nerve segment containing Schwann cell basal laminae can be used successfully as an allograft without any immunosuppressants and that exogenously applied bFGF can improve nerve regeneration by enhancing the growth of regenerating axons.

Fourier transform Raman spectra have been measured for pellets of sixteen kinds of linear low-density polyethylene (LLDPE) with short branches and one kind of PE without any branch. Before we tried chemometrics analysis, the Raman spectra of LLDPE were investigated by comparing them with the spectrum of PE in order to explore the effects of the branches on the Raman spectra. Partial least-squares (PLS) regression was applied to the Raman spectra in the 1600–600 cm−1region after multiplicative scatter correction (MSC) to propose a calibration model that predicts the density of LLDPE. The correlation coefficient was calculated to be 0.968, and the root mean square error of cross validation (RMSECV) was found to be 0.0018 g/cm3. The loadings plot of regression coefficients for the calibration model shows that, not only a sharp upward peak at 1417 cm−1corresponding to the CH2bending mode reflecting the crystallinity, but also a broad downward peak near 1308 cm−1corresponding to the amorphous board band of LLDPE plays a key role in the prediction of their density. The chemometrics study has deepened the analysis of the Raman spectra of LLDPE. For example, the detailed analysis of the principal component weight loadings plots has elucidated the existence of bands due to the CH3groups of branches and those arising from amorphous parts of LLDPE that are almost missing or hidden by other intense bands. In other words, the chemometrics analysis has enhanced spectral resolution.

Retroviral Gag protein is sufficient to produce Gag virus-like particles when expressed in higher eukaryotic cells. Here we describe the in vitro assembly reaction of human immunodeficiency virus Gag protein, which consists of two sequential steps showing the optimal conditions for each reaction. Following expression and purification, Gag protein lacking only the C-terminal p6 domain was present as a monomer (50 kDa) by velocity sedimentation analysis. Initial assembly of the Gag protein to 60 S intermediates occurred by dialysis at 4 degrees C in low salt at neutral to alkaline pH. However, higher order of assembly required incubation at 37 degrees C and was facilitated by the addition of Mg(2+). Prolonged incubation under these conditions produced complete assembly (600 S), equivalent to Gag virus-like particles obtained from Gag-expressing cells. Neither form disassembled by treatment with nonionic detergent, suggesting that correct assembly might occur in vitro. Electron microscopic observation confirmed that the 600 S assembly products were spherical particles similar to authentic immature human immunodeficiency virus particles. The latter assembly stage but not the former was accelerated by the addition of RNA although not inhibited by RNaseA treatment. These results suggest that Gag protein alone assembles in vitro, but that additional RNA facilitates the assembly reaction.

The objectives of this study were to establish an adult rat model for the late onset of radiation-induced cognitive dysfunction and to compare behavioural dysfunction with histopathological changes. While under anaesthesia, 30 rats (experimental group) were irradiated with a total dose of 40 Gy, given as eight fractions in 24 days. Another 30 rats (control group) underwent sham irradiation. The cognitive functions of all rats were evaluated at 6, 9 and 12 months after irradiation using the Morris water maze and passive avoidance tasks. Histopathological examination of these rats was carried out after the evaluation of cognitive functions was complete. At 6 and 9 months after irradiation there were no significant differences between the control and irradiated groups in passive avoidance and water maze tests. At 12 months after irradiation, the passive avoidance task revealed a deterioration of cognitive function in the experimental group. Histopathological observations revealed no abnormal findings in the irradiated brains at the light microscope level. Late onset cognitive dysfunction following cranial irradiation was observed in an adult rat model. Pathological investigations showed no abnormalities in the irradiated brains. These findings indicate that radiation-induced cognitive dysfunction can precede morphological changes in the brain or that they arise without them. The present model seems useful for elucidating the pathogenesis of radiation-induced cognitive dysfunction and for developing methods for therapy and prophylaxis.

Using the polymerase chain reaction, we have isolated numerous rat and human cDNAs of which the deduced amino acid sequences are highly homologous to the sequences of the extracellular domain of cadherins. The entire putative coding sequences for two human proteins defined by two of these cDNAs have been determined. The overall structure of these molecules is very similar to that of classic cadherins, but they have some unique features. The extracellular domains are composed of six or seven subdomains that are very similar to those of cadherins, but have characteristic properties. The cytoplasmic domains, on the other hand, have no significant homology with those of classic cadherins. Since various cDNAs with almost identical features were obtained also from Xenopus, Drosophila and Caenorhabditis elegans, it appears that similar molecules are expressed in a variety of organisms. We have tentatively named these proteins protocadherins. They are highly expressed in brain and their expression appears to be developmentally regulated. The proteins expressed from the two full‐length cDNAs in L cells were approximately 170 or 150 kDa in size, and were localized mainly at cell‐cell contact sites. Moreover, the transfectants showed cell adhesion activity.