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The Comparative Effectiveness Dementia and Alzheimer's Registry (CEDAR) trial demonstrated that individualized, multi-domain interventions improved cognition and reduced the risk of Alzheimer's disease (AD). As biological sex is a significant risk factor for AD, it is essential to explore the differential effectiveness of targeted clinical interventions in women vs. men.Patients were recruited from an Alzheimer's Prevention Clinic. Subjects with normal cognition, subjective cognitive decline, or asymptomatic preclinical AD were classified as "Prevention". Subjects with mild cognitive impairment due to AD or mild AD were classified as "Early Treatment." The primary outcome was the change from baseline to 18-months on the modified-Alzheimer's Prevention Cognitive Composite. Secondary outcomes included a cognitive aging composite, AD and cardiovascular (CV) risk scales, and serum biomarkers. Subjects who adhered to60% of recommendations in the CEDAR trial were included in this a priori sub-group analysis to examine whether individualized intervention effects were modified by sex (n=80).In the Prevention group, both women (p=0.0205) and men (p=0.0044) demonstrated improvements in cognition with no sex differences (p=0.5244). In the Early Treatment group, there were also no significant sex differences in cognition (p=0.3299). In the Prevention group, women demonstrated greater improvements in the Multi-Ethnic Study of Atherosclerosis risk score (MESA-RS) than men (difference=1.5, p=0.0013). Women in the Early Treatment group demonstrated greater improvements in CV Risk Factors, Aging and Incidence of Dementia (CAIDE) risk score (difference=2.3, p=0.0067), and the MESA-RS (difference=4.1, p0.001).Individualized multi-domain interventions are equally effective at improving cognition in women and men. However, personally-tailored interventions led to greater improvements in calculated AD and CV risk, and CV blood biomarkers, in women compared to men. Future study in larger cohorts is necessary to further define sex differences in AD risk reduction in clinical practice.

The hypocholesterolemic and anti-atherosclerotic effect of TS-962, a specific ACAT inhibitor, was investigated in a hamster model fed a high fat diet containing 10% coconut oil and 0.05% cholesterol. Lipid accumulated atherosclerotic lesions were detected by using oil red O staining in the lesion-prone aortic arch. A high dose, estimated to be 15 mg/kg, of TS-962 decreased serum cholesterol to normal levels with reduction of liver cholesterol contents below normal levels, and as a consequence, entirely inhibited the lipid accumulation in the aortic arch. Furthermore, a low dose, estimated to be 1.5 mg/kg, of TS-962 remarkably inhibited aortic lipid accumulation by 73% compared with the control group, without changing either serum cholesterol level or liver cholesterol content. These findings suggest that TS-962 is effective in the primary prevention of atherosclerosis by directly suppressing the formation of foam cells in arteries.

The Yangshao type pottery, made about 6000 yrs ago, was investigated by X-ray diffraction (XRD), and confirmed to be composed of quartz, feldspar, muscovite and calcite. A black pigment on it was assumed to be (Mn, Fe)3O4 from Particle Induced X-ray Emission (PIXE) and XRD experiments. Firing temperature of the pottery was assumed to be less than 600°C from a heating experiment of the fragment of the pottery.

Hydrophobized polysaccharides, which were partly substituted by hydrophobes such as cholesterol, formed a hydrogel nanoparticle by their self-assembly in water. The size, density and colloidal stability of the nanoparticle were controlled by changing the substitution degree of hydrophobes and the hydrophobicity. The hydrophobized polysaccharides were further functionalized by conjugation of cell-specific saccharide, thermoresponsive polymer or polyethylene oxide. The hydrophobized polysaccharides interacted with various soluble proteins or other molecular assemblies, such as monolayer, black lipid membrane, liposome and oil-in-water emulsion. Such supramolecular assemblies with hydrophobized polysaccharides were utilized in biotechnology and medicine.

In vitro and in vivo anti-human T lymphotropic virus type 1 (HTLV-1) cellular immunity was examined by immunizing rats with a truncated hybrid protein (228 amino acids) of gag and env of HTLV-1 produced by Escherichia coli. Animals were immunized with the hybrid protein reconstituted into mannan-derivative-coated liposomes (gag-env-lipo). In vitro sensitization with a HTLV-1-positive cell line, TARS-1, of spleen cells obtained from these animals generated killer cells specific for syngeneic HTLV-1-positive cells. No killer activity was generated when spleen cells were obtained from animals immunized with the hybrid protein alone, the liposome alone, or the hybrid protein reconstituted into conventional liposomes with no polysaccharide coating. Killer cells were CD8+ CTL restricted to MHC class I. Analysis of CD8+ and CD4+ subsets in spleens showed the existence of primed CD8+ T cells in animals immunized with gag-env-lipo. Rats immunized with gag-env-lipo displayed accelerated rejection of TARS-1 but not of two other HTLV-1-negative tumor lines. Injection of carrageenan into animals strongly inhibited generation of killer cells, which indicates the necessity of macrophages for priming of CD8+ T cells with gag-env-lipo. Injection of carrageenan also cancelled in vivo immunity against HTLV-1+ cells induced with gag-env-lipo. These results, taken together, indicate that exogenous protein reconstituted into appropriate liposomes can effectively prime MHC class I restricted CD8+ T cells in vivo with macrophage dependency.

This paper proposes a predicate nameddosim which provides a new function for parallel execution of logic programs. The parallelism achieved by this predicate is a simultaneous mapping operation such as bagof and setof predicates. However, the degree of parallelism can be easily decided by arranging the arguments of the dosim goal. The parallel processing system with dosim was realized on a tight-coupled multiprocessor machine. To control the degree of parallelism and reduce the amount of memory required for execution, we introduce the grouping method for the goals executed in parallel and some variations of the dosim predicate. The effectiveness of the proposed method is demonstrated by the results of the execution of several applications.

New enzyme-responsive micellar systems in which an enzymatic reaction controls the amphiphilicity of the surfactants were reported. The surfactants in our study consist of a short alkyl chain and a maltooligomer as a primer which can be synthesized enzymatically. In the presence of phosphorylase and alpha-D-glucose-1-phosphate (G1P), the elongation reaction of the saccharide chain proceeds from the non-reducing 4-OH terminus of the glucan chain. Amylose-primer surfactants (C12MP) where an alkyl group (C12) is linked to the reduced terminus of maltopentaose form micelles in water, which are dissociated upon the enzymatic elongation reaction of the sugar moiety. The micelle-to-vesicle transition of mixed lipid/ primer systems can be controlled by using this property. This new type of transition system can be used in the reconstitution of transmembrane proteins to liposome.

The purpose of this study was to investigate the effect of coronary arterial bypass grafting (CABG) with gastroepiploic artery (GEA) on gastric intramucosal pH and systemic inflammation.retrospective study.University hospital.22 patients underwent CABG.the GEA group (n=13) received CABG with the GEA graft. The non-GEA group (n=9) received conventional CABG without the GEA graft.gastric intramucosal pH (pHi) and carbon dioxide tension (PrCO(2)) were assessed by capnometric air tonometry. The difference between PrCO(2) and PaCO(2), PCO(2)-gap, was also determined. Systemic inflammatory responses were evaluated by serum interleukin-6 (IL-6) and leucocyte counts. Hemodynamics, oxygen delivery index (DO(2)I) and uptake index (VO(2)I) were monitored with catheters in the radial and pulmonary arteries (thermodilution).The duration of aortic cross-clamping and cardiopulmonary bypass was similar in both groups. Both groups did not show any significant difference in gastric pHi, PCO(2)-gap, systemic inflammation and hemodynamics.Our findings suggest that CABG using the GEA graft does not disturb gastric mucosal perfusion, and that laparotomy for the GEA graft does not aggravate systemic oxygen demand-supply imbalance or systemic inflammatory responses induced by hypothermic CPB. CABG with the GEA graft does not seem to pose an additional risk and is a safe technique compared with conventional CABG with regard to pHi and systemic inflammation.

We have previously shown that a novel hydrophobized polysaccharide/oncoprotein complex vaccine can induce immune responses against the HER2/neu/c-erbB2 (HER2) expressing tumors. Bone marrow-derived dendritic cells (DCs), as antigen presenting cells (APCs), are the first candidates for presentation of tumor antigens. The aim of this study was to see whether DCs are able to elicit antigen specific host immune responses by stimulating the proliferation of T cells after exposure to cholesteryl group bearing pullulan (CHP) and HER2 protein complex. Vaccination by CHP-HER2 complex was as effective as cholesteryl group bearing mannan (CHM) and HER2 complex on which we reported previously. Immunization of mice with HER2 expressing CMS17HE tumor cells generated both CD4+ T cells and CD8+ T cells reactive with CHP-HER2 complex pretreated DCs. In addition, immunization with either CHP-HER2 complex or HER2 protein alone could also generate both CD4+ T cells and CD8+ T cells specifically reactive with CHP-HER2 complex pretreated DCs. The complete rejection of tumors occurred when immunization with CHP-HER2 complex pretreated DCs was started 10 days after tumor inoculation. Therefore, bone marrow-derived DCs pretreated with hydrophobized polysaccharide/oncoprotein complex are a powerful tool for enhancing the effectiveness of oncoprotein for anti-tumor vaccination, opening new options for immune cell therapy.

To elicit specific cellular immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the MHC class I pathway constitutes a central issue. We report here a novel formula of hydrophobized polysaccharide nanoparticles, which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway. A protein consisting of the 147 amino-terminal amino acids of oncogene erbB-2/neu/HER2 (HER2) was complexed with two kinds of hydrophobized polysaccharides, cholesteryl group-bearing mannan (CHM) and cholesteryl group-bearing pullulan (CHP), to form nanoparticles (CHM-HER2 and CHP-HER2). CHM-HER2 and CHP-HER2 were able to induce CD3+/CD8+ CTLs against HER2-transfected syngeneic fibrosarcoma cell lines. In contrast, the oncoprotein alone failed to do so. These CTLs were Kd-restricted and specifically recognized a peptide (position 63-71) that was a part of a truncated HER2 protein used as an immunogen. In addition, vaccination by CHM-HER2 complexes led to a strongly enhanced production of IgG antibodies against HER2, whereas vaccination with HER2 proteins alone resulted in a production of antibodies at a marginal level. Mice immunized with CHM-HER2 or CHP-HER2 before tumor challenge successfully rejected HER2-transfected tumors. The complete rejection of tumors also occurred when CHM-HER2 was applied not later than 3 days after tumor implantation. In the effector phase of in vivo tumor rejection, CD8+ T cells played a major role. The results suggest that a sort of hydrophobized polysaccharide may help soluble proteins to induce cellular immunity as well enhance humoral immunity; hence, such a novel vaccine may be of potential benefit to cancer prevention and cancer therapy.

Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 96 samples of different origin tested, two were shown to inhibit the growth of HIV in vitro. One of the positive samples (plant origin) has hopeful signs, as the ranges of effective doses are wider than those of most of positive samples which had been found by us.

To pursue a systemic administration of alpha-linolenic acid (ALA), which is a selective cytotoxic agent, we formulated an ALA o/w-emulsion stabilized by cholesterol-bearing pullulan (CHP-55-2.1) and trioctanoylglyceride (TriC8). This emulsion was stable even in the presence of bovine serum albumin (BSA). Peroxidation of ALA was drastically depressed by the emulsification using CHP. In addition, cytotoxic effect of the CHP/ALA/TriC8-emulsion against human colon cancer cell (RPM14788) was much higher than that of free ALA. However, no significant difference was observed in cell internalization efficiency of ALA between the two. These results suggest that difference in the cytotoxicity between the CHP/ALA/TriC8-emulsion and free ALA may come from difference in the intracellular behavior of ALA.

Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 246 samples of different origin tested, six were shown to inhibit the growth of HIV in vitro. Two of the positive samples have hopeful signs, as the ranges of effective doses are wider than those of most of positive samples which had been found by us.

Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 138 samples tested, two were found to inhibit the growth of HIV in vitro. Neither of the positive samples has hopeful signs, as the ranges of effective doses of the samples are very narrow.

SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly post-translational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand–glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.

Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 191 samples tested, seven were found to inhibit the growth of HIV in vitro. Four of seven have hopeful signs, as the ranges of effective doses of the samples are wide.

Preliminary screening for antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 154 samples tested, nine were found to inhibit the growth of HIV in vitro. One of nine has a hopeful sign, as the range of effective doses of the sample is wide.

Preliminary screening for antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 106 samples tested, five were found to inhibit the growth of HIV in vitro. Two of five have a hopeful sign, as the range of effective doses of the samples is wide.

Pituitary apoplexy is characterized by a wide spectrum of clinical features. A quite rare case of painless thyroiditis, hypopituitarism and central diabetes insipidus (DI) followed by pituitary apoplexy was presented. A 61-year-old woman was admitted to our hospital in May, 1986 because of marked general malaise, polydipsia and weight loss which became progressively worse. Four months earlier she had experienced episodes of abrupt onset of severe headache associated with nausea and blurring vision. Physical examinations revealed a fine tremor, dry skin and nervousness. The thyroid gland was not palpable. Visual fields were intact. Her blood pressure was 105/64 mmHg with variable tachycardia. The routine laboratory studies were normal or negative except for hypoalbuminemia, hypocholesterolemia and hypernatremia. Erythrocyte sedimentation rate was 12 mm/hr. An impairment in corticotropin secretion was suspected from the low plasma cortisol and the low urinary excretion of 17-OHCS and the sufficient response to ACTH. Basal levels of GH and gonadotropin were also low, and responses to the stimulation tests (Insulin-stress, L-DOPA, and LH-RH) were all blunted. Brain computed tomographic scan and magnetic resonance imaging demonstrated a suprasellar mass that, after infusion, developed peripheral ring-like enhancement and large hyperintense pituitary mass, respectively. A diagnosis of pituitary apoplexy with anterior pituitary failure was made. However, the initial levels of thyroid hormones showed elevated as follows: Free T3 7.6 pg/ml, Free T4 3.3 ng/dl and T3-resin uptake 41.1%. TSH responses to TRH were all suppressed. TSH receptor antibody (TBII) was negative. Both antithyroglobulin and antimicrosomal antibodies were repeatedly positive. A thyroid scan with 99mTc revealed no uptake in the thyroid area. These findings led us to the diagnosis of "painless autoimmune thyroiditis". She had become hypothyroid without any medication. At that time radioactive 99mTc and 123I uptakes increased significantly. When hydrocortisone was substituted, daily urine output abruptly increased to about 10 liters with low osmolality, and the presence of DI was suspected. This diagnosis was confirmed by water deprivation and hypertonic saline infusion tests and subsequent pitressin test. She is currently quite well on L-thyroxine, hydrocortisone and desmopressin (1988). This association with pituitary apoplexy must be a rare occurrence, as a literature search has failed to find a similar case. The pathogenetic trigger of "painless thyroiditis" in this case may be responsible for some immunological change due to secondary adrenal insufficiency after pituitary apoplexy.

Preliminary screening for antiviral AIDS drugs has been carried out, using three different in vitro assay systems. Among 105 samples tested, 13 were found to inhibit the growth of HIV in vitro. Eleven of 13 were well-known anti-HIV chemicals, while the remaining two of plant origin were new chemicals whose anti-HIV activities have not been reported elsewhere.

1. Out of 100 hospitalized patients with cerebral palsy, 14 patients with dislocated and subluxated hips have been studied.2. The age at which dislocation occurred in 6 of 7 hips was before 4 years, while the age at which subluxation occurred in 7 of 9 hips was after seven years.3. It seemed that the tight and spastic adductors was the most important factor in the production of dislocation, but congenital dislocation of the hip was associated with paralytic dislocation in some of our cases.4. The treatment and results were presented.

A girl aged three years was admitted because of the pathologic fractures of the bilateral femoral necks. She had splenomegaly, sequint, mild generalized lymphadenopathy and anaemia. There was a past history of splenectomy two years ago. Laboratory test revealed a marked increase of acid phosphatase and decrease of blood cholesterol, and Gaucher's cells were observed in the bone marrow taken at the osteosynthesis of the femoral neck.

Sixteen cases of combined lesion of the median and ulnar nerve were treated from 1967 to 1977. The follow-up results were classified by Higher's and Zachary's criteria. The following results were obtained:1) Of 4 cases after neurolysis, all recovered near-normal sensory and motor function both in median and ulnar nerve.2) In 9 cases after nerve suture, 77.7% showed a recovery of over-M3, 55.5% over-+2 and an useful recovery was obtained in 55.5% in median nerve, 33.3% were in category of over-M+2, 66.0% in over-S+2 and an useful recovery was regained in only 33.3% in ulnar nerve.

We have treated a patient with hand injury caused by the injection of paint from a high pressure spray gun. The patient was a seventeen-year-old right handed painter, who was injured to the base of the left thenar, and admitted 7 clays after the injury. On admission, lacal findings showed wide spreading swelling and necrosis of the subcutaneous tissue of the whole hand, and partial necrosis of the skin. Wide debridement and decompression incision were carried out and, moreover, he was treated with hyperbaric oxygen therapy four times during the following 7 days. Swelling was promptly subsided and he was discharged 8 weeks after the operation leaving the small granulated wound at the thenar. At one year and four months after the operation, he had no functional disturbance of the hand except for mild restriction of extention of the IP joint of the thumb. We discussed the mechanism of effects of hyperbaric oxygen therapy for the spray gun injury.

Ni-S electrodeposits have been produced by two plating methods, direct current (dc) and pulse current (pc) methods, in a nickel sulfate bath. The structure of electrodeposited layers has been studied in detail by X-ray diffraction methods. The electro-deposited layer produced by the dc method contains 21 at% S and consists of a microcrystalline state of Ni alloy. However, the layer by the pc method contains 46 at% S and consists of an amorphous alloy.

We reported a case with epiphyseal separation of the distal ulna which could not be reduced by nonsurgical manipulation due to interposition of the ext. carpi ulnaris tendon. The case was a 13-year-old boy who injured by falling clown from a running motorbike. X-ray findings showed markedly separated distal epiphysis of the bilateral ulna with fracture of the distal radius. In spite of manipulation under anesthesia, the epiphyseal separations were irreducible. Operative findings showed that the ext. carpi ulnaris tendons were interposed between the separated ulnar fragments. Each radius and ulna were fixed by Kirschner wires following surgical reduction.