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Biomedical subjects

Y Ono

Publications and source records attributed to Y Ono.

At least 19 recordsLinked to original sources

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans

Carbonic anhydrase in the membrane of the endoplasmic reticulum of male rat liver.

We have prepared subcellular fractions of male rat liver homogenate by the method of Lewis and Tata [Lewis, J. A. & Tata, J. R. (1973) J. Cell Sci. 23, 447-459], further purifying the membranes of the microsomal fraction by exposure to 0.01% Triton X-100 and centrifugation. We determined the purity of the fractions with marker enzymes and measured carbonic anhydrase (CA; EC 4.2.1.1) activity in intact and solubilized particulates with 18O exchange between CO2/HCO3- and water. We measured the concentration of CA by titration with a sulfonamide inhibitor, ethoxzolamide, obtaining an average value of 3.8 mumol/mg of microsomal membrane protein. The equilibrium constant for binding ethoxzolamide was 0.49 x 10(-9) M. The Km for CO2 was 1.7 mM and the turnover number was 560,000 sec-1, characterizing this as a membrane-bound, high-activity isozyme of type IV. By electron microscopy of tissue sections after staining with a cobalt precipitation technique, CA was seen in small cytoplasmic vesicles in hepatocytes and in microsomal particles and membranes. There was a sulfonamide-resistant (isozyme type III) and a sulfonamide-sensitive (isozyme type II) CA in the cytosol but none in the rapidly sedimenting endoplasmic reticulum. We conclude that there is no CA normally within the matrix of the cell endoplasmic reticulum but that the CA type III found in the microsome may have been captured from the cytosol during resealing. Thus the adult male rat hepatocyte contains CA type IV in the membrane of the endoplasmic reticulum and CA type II and CA type III in the cytoplasm.

Animals

Control of Drosophila Sex-lethal pre-mRNA splicing by its own female-specific product.

Drosophila melanogaster somatic sexual differentiation is accomplished by serial function of the products of sex-determination genes. Sex-lethal (Sxl), is one such gene. It is functionally expressed only in female flies. The sex-specific expression of this gene is regulated by alternative mRNA splicing which results in either the inclusion or exclusion of the translation stop codon containing third exon. Although previous genetic and molecular analyses suggest that functional Sxl expression is maintained by a positive feedback loop, where the female-specific Sxl product promotes the synthesis of its own female-specific mRNA, the mechanistic details of such regulation have remained unclear. We have developed a cotransfection system using Drosophila cultured (Kc) cells in which Sxl primary transcripts are expressed with or without the female specific Sxl product. Here we show that the female-specific Sxl product induces the synthesis of its own female-specific mRNA by negative control of male-specific splicing. Deletion, substitution, and binding experiments have demonstrated that multiple uridine-rich sequences in the introns around the male-specific third exon are involved in the splicing regulation of Sxl pre-mRNA.

Animals

Cell division arrest induced by phorbol ester in CHO cells overexpressing protein kinase C-delta subspecies.

Several lines of CHO cells stably overexpressing protein kinase C (PKC) subspecies to various extents were established by the DNA-mediated transfer. Upon treatment with phorbol 12-myristate 13-acetate, the growth of the cells expressing the PKC-delta subspecies was markedly inhibited, whereas cell lines expressing PKC-alpha, PKC-beta II, and PKC-zeta subspecies were not significantly affected. Flow cytometric analysis indicated that all cell lines overexpressing PKC-delta subspecies accumulated in G2/M phase in response to phorbol 12-myristate 13-acetate. In these arrested cells, dikaryons were predominant, implying that phorbol ester-induced inhibition of cell division is specific to telophase. These results suggest PKC-delta subspecies may play a role in the normal cell cycle progression.

Animals

Y-29794--a non-peptide prolyl endopeptidase inhibitor that can penetrate into the brain.

A novel non-peptide prolyl endopeptidase (PPCE) inhibitor, Y-29794, has been identified. Y-29794 selectively and competitively inhibited rat brain PPCE (Ki = 0.95 nM) in a reversible manner. Ex vivo study demonstrated that Y-29794 could penetrate into brain to exhibit dose-dependent and long-lasting inhibition. Furthermore, Y-29794 was found to potentiate the effect of TRH on the release of ACh in the rat hippocampus. These results indicate that Y-29794 is an orally active, potent and specific PPCE inhibitor and should be of value in studies on the physiological role of the enzyme in neuropeptide metabolism especially in memory process.

Acetylcholine

EBV increases phosphoinositide kinase activities in human B cells.

To determine whether EBV affects phosphoinositide kinase activities of human B cells, we compared the activities between EBV- and EBV+ human B cell lymphoma lines. The two types of human B cells contained both phosphatidylinositol (PtdIns) 4-kinase and phosphatidylinositol 4-phosphate (PtdIns(4)P) kinase activities irrespective of the presence of EBV. However, both activities were increased in EBV+ cells compared to EBV- cells. The increases were associated with neither altered Km values for substrates nor altered elution profiles in DEAE-cellulose chromatography. Furthermore, expression of a latent EBV protein, EBV nuclear Ag1 (EBNA1) in BHK cells by the transfection of EBNA1 DNA was accompanied by increased PtdIns 4-kinase and PtdIns(4)P kinase activities. These increases also were not associated with altered Km values for substrates. However, phospholipase C activity was altered in neither EBV+ cells nor in EBNA1-expressing cells. These results indicate that EBV selectively increases the two phosphoinositide kinase activities in human B cells, although the viral gene product has no intrinsic phosphoinositide kinase activity. PtdIns 4-kinase and PtdIns(4)P kinase cooperatively synthesize PtdIns 4,5-bisphosphate, the major source of 1,2-diacylglycerol and inositol 1,4,5-triphosphate, the two second messengers in transducing signals for cell activation. Such increase therefore may play a role in EBV-induced human B cell activation.

1-Phosphatidylinositol 4-Kinase

[Electron-microscopic study on the effect of an expandable metallic stent placement in the aortic wall].

As part of a series of basic experiments on using metallic stents for treatment of vascular stenosis, a chronological examination of changes in dog aorta following implantation of a self-expandable metallic stent was conducting using transmission and scanning electron microscopy. The Giantruco stent was placed in the abdominal aorta via the right carotid artery. One week after insertion, the aortic intima was depressed and degenerative changes observed in both endothelial and medial smooth muscle cells. After 2 weeks, except for the bend portion, the stent was covered with neointima. The neointimal surface was covered by premature endothelial cells with abundant microvilli and prominent nuclear protrusions. Under the endothelial cells, immature mesenchymal cells, such as fibroblast, were scattered throughout the edematous intercellular space. At 4 weeks, the stent was completely covered by neointima and the endothelial cells had flattened and few microvilli were in evidence. In this thickened intima, premature smooth muscle cells with myofilaments and basement membranes were observed but, around them, few collagen fibers and only occasional elastic fibers were found. At 6 weeks, the intimal surfaces were flat and smooth with a slight intimal elevation over the stent. No thrombus was observed throughout the period of the experiment. The above results indicate that dilation using metallic stents may be a useful method for treatment of vascular stenosis.

Animals

Characterization of the 5'-flanking region of the human brain-derived neurotrophic factor gene.

The 5'-flanking region of the human brain-derived neurotrophic factor (BDNF) gene was isolated from a human placental genomic library using the cDNA fragment for the 5'-noncoding region of human BDNF as a probe. A 3.2 Kbp genomic fragment containing the 5'-flanking region, the first exon and a portion of the first intron was isolated and sequenced. The transcriptional initiation site, identified by S1 nuclease mapping, was located 26 bp downstream from the TATA-like sequence. Several expression plasmids, in which the BDNF promoter regions were fused to the chloramphenicol acetyltransferase (CAT) gene, were constructed. Transient expression in human glioma Hs683 cells demonstrated that a fragment of about 0.5 Kbp from the transcriptional initiation site was sufficient for promoter activity.

Base Sequence

Prolonged decrease of serum calcium concentration by murine gamma-interferon in hypercalcemic, human tumor (EC-GI)-bearing nude mice.

Murine gamma-interferon (MuIFN-gamma) is a potent inhibitor of bone resorption induced by interleukin 1 and parathyroid hormone-related protein in vitro. To investigate whether MuIFN-gamma is also effective in vivo, the cytokine was injected s.c. into hypercalcemic, tumor (EC-GI)-bearing nude mice, in which parathyroid hormone-related protein and interleukin 1 alpha are synergistically responsible for causing humoral hypercalcemia. When MuIFN-gamma was injected s.c. at a dose of 1 to 20 x 10(4) units for 5 days consecutively, serum calcium concentrations in the tumor-bearing mice decreased in a dose-dependent manner. The minimal effective dose was 5 x 10(4) units/mouse. Unlike calcitonin, which decreased the serum calcium concentration for only 1 to 2 days despite continuous daily injections, MuIFN-gamma decreased it for more than 7 days even after the injections had been stopped. Human gamma-interferon was completely ineffective. The decrease in serum calcium concentration was accompanied by a decrease in urinary calcium excretion. Histological examination of the femur revealed a decreased number of osteoclasts in the MuIFN-gamma-treated mice. Furthermore, MuIFN-gamma, when injected into nude mice or normal mice at a dose of 15 x 10(4) units for 3 days, almost completely abolished the formation of multinucleated osteoclast-like cells in vitro. These findings suggest that MuIFN-gamma suppresses the formation and maturation of osteoclasts and inhibits osteoclastic bone resorption, resulting in the prolonged decrease of serum calcium concentration seen in hypercalcemic, tumor-bearing nude mice. Therefore, bone resorption inhibitors like MuIFN-gamma, which ameliorate humoral hypercalcemia without an escape phenomenon, are potentially useful for the treatment of malignancy-associated hypercalcemia.

Animals

Combination chemotherapy for advanced urothelial-tract carcinoma.

Between December 1982 and November 1990, 31 patients with advanced urothelial carcinoma were treated with one of two combination chemotherapy regimens. A total of 20 patients were treated with 3 mg/m2 mitomycin C and 300 mg/m2 cyclophosphamide given intravenously every 10-14 days and with 180 mg/m2 5-fluorouracil (5-FU) given intravenously every day for as long as possible (CF-Mito regimen). After the patient had been discharged from the hospital, the same treatment with CF-Mito was performed except that 180 mg/m2 5-FU was replaced by 400 mg/m2 UFT (a mixture of tegafur and uracil) given orally. A total of 11 patients whose tumor had relapsed during the first-line treatment were given 60 mg/m2 cisplatin, 40 mg/m2 Adriamycin, and 40 mg/m2 methotrexate intravenously every 28 days (PAM regimen). In all, 20 patients received 4-44 (mean, 9.7) courses of CF-Mito over a period of 1.5-24 (mean, 5.3) months. The results obtained in these 20 patients with evaluable lesions included no complete remission (CR), 4 partial remissions (PRs), 9 cases of stable disease (SD), and 7 cases of progressive disease (PD). The PR duration was 1.5-22 (mean, 7.5) months. The side effects encountered in this group included anorexia, nausea, vomiting, myelosuppression, diarrhea, stomatitis, liver damage, and heart failure. In all, 11 patients received 3-7 (mean, 4.1) courses of PAM over a period of 3-14.5 (mean, 5.2) months. All 11 patients had evaluable lesions, and their responses included no CR, 5 PRs, 3 cases of SD, and 3 cases of PD. The PR duration was 1-3 (mean, 1.6) months. The side effects encountered in this group included anorexia, nausea, vomiting, myelosuppression, heart failure, and hair loss.

Adult

Late death after arterial switch operation for transposition of the great arteries.

Fifty-nine patients survived for more than 1 month after an arterial switch operation (ASO). Diagnoses in these patients included transposition of the great arteries in 27, transposition of the great arteries with ventricular septal defect in 28, and double-outlet right ventricle in four. There were six late deaths (10%) during the follow-up period, and all of them occurred suddenly and unexpectedly. Four of the six late deaths were in patients who had undergone ASO in the neonatal period. Late deaths occurred from 40 days to 10 months after the operation. Autopsies were performed in all six patients. The cause of these late deaths was acute myocardial infarction. Five patients died of subendocardial infarction resulting from stenosis of the left main coronary artery. On pathologic examination, a fibrocellular intimal thickening was noted at the proximal region of the right and left coronary arteries, which resulted in 80% stenosis on average.

Abnormalities, Multiple

Endopyeloureterotomy via a transpelvic extraureteral approach.

Endopyeloureterotomy has been accepted as a procedure to relieve obstruction of the ureteropelvic junction and upper ureteral stenosis. However, in patients with a long stenotic segment poor results are often obtained with the conventional technique. To resolve this problem we developed a new technique using a 22F urethrotome and a transpelvic extraureteral approach. In this technique the renal pelvis was incised for 1 to 1.5 cm. from the ureteropelvic junction in the direction of the parenchyma using the cold knife of the urethrotome under direct vision. For upper ureteral stenosis the dilated pelvic and ureteral posterolateral walls were incised 1 to 1.5 cm. from the stenotic segment toward the ureteropelvic junction. Then, the stenotic segment was treated with the urethrotome after it was advanced into the retroperitoneal space through the incision in the renal pelvis. We treated 21 patients with the new technique between August 1988 and August 1990. Our series included 3 patients with the high insertion type of ureteropelvic junction obstruction and 4 with a long stenotic segment. The success rate was 95% without any severe complication. These results indicate that our new technique could become a useful procedure for endopyeloureterotomy.

Adolescent

Breed differences in the histochemical properties of the M. iliotibialis lateralis myofibre of domestic cocks.

1. Reduced nicotinamide adenine dinucleotide dehydrogenase (NADH-DH) activity in the M. iliotibialis lateralis was compared histochemically among 7 breeds of cocks. This muscle was composed only of Type-IIA and -IIB fibres. 2. Apparent breed differences were observed in muscle development, the NADH-DH activity in every fibre type, fibre type distribution and fibre diameters. 3. From the results of this study, it was concluded that the muscle characteristics of various breeds were based not only on the fibre type composition, but also the different activities of oxidative enzyme in every type.

Animals

A prospective study of human herpesvirus-6 infection in renal transplantation.

Sixty-five kidney transplant recipients and their (22 living related and 43 cadaveric) donors were studied prospectively to determine the relationship between kidney transplantation and human herpesvirus-6 (HHV-6) infection. The virus isolation from peripheral blood and other tissues and sequential determination of neutralizing antibodies to HHV-6 were performed during 3 months following the transplantation. All of the donors and their recipients examined had neutralizing antibodies to HHV-6 at the time of renal transplantation and the virus was not isolated from them. HHV-6 was isolated from 3 renal tissues (2 living related and 1 cadaveric) obtained during transplant surgery, but not from their blood at that time. HHV-6 viremia occurred in 9 (14%) of the 65 recipients around 2 to 4 weeks after the transplantation. An additional 27 recipients showed a significant rise in the antibody titer. Thus, the infection with HHV-6 was confirmed in 36 (55%) of the 65. These results indicate that the virus is activated in many cases in the early posttransplant period and that HHV-6 establishes in vivo latency in the kidney tissue. There was no correlation between HHV-6 infection and acute rejection or the antirejection prophylaxis.

Adolescent

IgM neutralizing antibody responses to human herpesvirus-6 in patients with exanthem subitum or organ transplantation.

The assay for detecting IgM neutralizing (NT) antibody activity to human herpesvirus-6 (HHV-6) was developed by using pretreatment of blood sample with staphylococcal protein A. The activity was mostly present in IgM fractions of serum but not in IgA fractions separated by ultracentrifugation. The assay was used for seroepidemiological studies for HHV-6 infection. In primary HHV-6 infection, IgM NT antibodies appeared 5 to 7 days after onset of exanthem subitum, reached maximum titers at 2 to 3 weeks, and tended to decline to undetectable levels after 2 months. In contrast, reactivation of HHV-6 observed in organ transplants showed somewhat greater degree of IgM NT antibody responses that persisted for 2 to 3 months and became undetectable 5 to 6 months after transplantation. The level and persistence of NT antibody titers measured by the conventional method was generally greater than those of the IgM titers. The prevalence of the IgM NT antibodies was examined in healthy individuals. The antibody was first detected at 4 to 7 months of age (5%), reached maximum level at 8 to 11 months (40%), and was detectable by 4 to 6 years (17%). A few (4 to 5%) of adolescents and adults were positive for the antibody.

Adolescent

Establishment of stable cell lines producing anti-Pseudomonas aeruginosa monoclonal antibodies and their protective effects for the infection in mice.

Human-human hybridomas producing monoclonal antibodies (MoAbs) specific for five major serotypes of Pseudomonas aeruginosa were developed by fusing P. aeruginosa primed and Epstein-Barr virus-transformed cells with human myeloma P109 cells using polyethyleneglycol. The MoAbs which were produced by the hybridomas were protective against lethal intraperitoneal (i.p.) challenge of P. aeruginosa (10 LD50) in mice. The 50% effective dose (ED50) values of MoAbs ranged from 0.5 to 10.2 micrograms/mouse and were 26 to 240 times more protective than a commercial human IgG preparation. MoAb administration to mice promoted bacterial clearance in peritoneal cavity, and prevented bacterial invasion into blood in the way of increasing both the number of bacteria trapped by a macrophage and the ratio of macrophages that trapped bacteria. MoAbs also showed protective effects against lethal infection of P. aeruginosa in the mice which were decreased in polymorphonuclear cells (PMN) by cyclophosphamide (CY). All MoAbs showed serotype-specific binding to the clinical isolates of P. aeruginosa as well as to the immunized strains. The hybridoma cell lines maintained their capacity to produce MoAb continuously for more than 12 months and produced 10 to 60 micrograms MoAbs per 10(6) cells in 24 hr. It is practicable to use these cell lines for large-scale production of anti-P. aeruginosa MoAbs and such MoAbs must be useful for the therapeutics of patients with P. aeruginosa infection.

Animals

Age-related changes in occipital alpha rhythm of adults with Down syndrome.

A power spectral analysis was performed on occipital EEGs recorded from 36 Down Syndrome (DS) subjects aged 15 to 54 and compared with two control groups; 47 healthy volunteers (Control) and 42 mentally retarded people without DS (MR). The frequencies of occipital alpha rhythms of DS showed a significant inverse correlation with chronological age, while Control and MR did not. The average frequencies of DS were significantly low even in the youngest age-group in comparison with those of Control, and also decreased in the age-groups of 35 and older compared with MR. It was considered that a slowing of alpha rhythm was a manifestation of premature aging that occurred in the underdeveloped brains of DS.

Adolescent