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Biomedical subjects

S Saito

Publications and source records attributed to S Saito.

At least 73 records · Page 4Linked to original sources

Beta-chemokine, macrophage inflammatory protein-1beta (MIP-1beta), is highly expressed in diffuse type human gastric cancers.

Chemokines have been shown to be expressed in some malignant or precancerous tissues. However, the role of these chemokines on tumor development or progression is not clear. The expression patterns of chemokines in gastric cancer tissues were examined in 86 surgically resected samples using immunohistochemistry. Macrophage inflammatory protein-1beta (MIP-1beta) was clearly detected in many gastric carcinoma cells. In most of the differentiated carcinomas, intracellular localization of MIP-1beta was detected in more than 5% of cancer cells, although the percentages of MIP-1beta-positive cells differed among each sample. Undifferentiated carcinomas showed contrasted staining pattern between solid type and non-solid (diffuse) type. MIP-1beta was totally absent in all the poorly differentiated carcinomas with solid type growth pattern (por1). In contrast, MIP-1beta was highly expressed in all of the non-solid type of poorly differentiated carcinoma (por2) and signet-ring cell carcinoma samples. In particular, MIP-1beta was strongly stained in carcinoma cells at the front of invasive lesions. In 43 diffuse type undifferentiated cancers, tumors with high expression of MIP-1beta exhibited significantly more lymph node metastasis. Our results suggest a possibility that MIP-1beta may be related to the scattering and invasion step of gastric carcinoma cells with undifferentiated phenotype.

Chemokine CCL4↗

A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs.

In a previous study, we used subcutaneous LY80 tumours (a subline of Yoshida sarcoma), Sato lung carcinoma, and methylcholanthrene-induced primary tumours, to demonstrate that a novel water-soluble combretastatin A-4 derivative, AC7700, abruptly and irreversibly stopped tumour blood flow. As a result of this interrupted supply of nutrients, extensive necrosis was induced within the tumour. In the present study, we investigated whether AC7700 acts in the same way against solid tumours growing in the liver, stomach, kidney, muscle, and lymph nodes. Tumour blood flow and the change in tumour blood flow induced by AC7700 were measured by the hydrogen clearance method. In a model of cancer chemotherapy against metastases, LY80 cells (2x10(6)) were injected into the lateral tail vein, and AC7700 at 10 mg x kg(-1) was injected i.v. five times at intervals of 2 days, starting on day 7 after tumour cell injection. The number and size of tumours were compared with those in the control group. The change in tumour blood flow and the therapeutic effect of AC7700 on microtumours were observed directly by using Sato lung carcinoma implanted in a rat transparent chamber. AC7700 caused a marked decrease in the tumour blood flow of all LY80 tumours developing in various tissues and organs and growth of all tumours including lymph node metastases and microtumours was inhibited. In every tumour, tumour blood flow began to decrease immediately after AC7700 administration and reached a minimum at approximately 30 min after injection. In many tumour capillaries, blood flow completely stopped within 3 min after AC7700 administration. These results demonstrate that AC7700 is effective for tumours growing in various tissues and organs and for metastases. We conclude that tumour blood flow stanching induced by AC7700 may become an effective therapeutic strategy for all cancers, including refractory cancers because the therapeutic effect is independent of tumour site and specific type of cancer.

Animals↗

Coherent magnetic oscillation in the spin ladder system alpha(')- NaV2O5.

We report the first observation of coherent magnetic excitations in a spin ladder system NaV2O5 by using femtosecond time-domain spectroscopy. A pronounced coherent oscillation is observed at 127 cm(-1) (nearly twice the spin gap energy) and assigned to a two-magnon bound state, based on the temperature dependence of the intensity below the charge ordering phase transition at T(C) = 34 K. This mode can be observable only when circularly polarized light is used as a pump or a probe beam, suggesting that it corresponds to a spin-flip excitation from the singlet ground state. A phonon mode strongly coupled to the spin state is also found at 303 cm(-1).

Journal Article↗

Analysis of HLA in children with gelatin allergy.

Systemic immediate reactions including anaphylaxis to gelatin in vaccines have been reported. However, the number of such reports is very small compared with the number of children exposed to gelatin. The present study was designed to investigate whether susceptibility or resistance to gelatin allergy is associated with human leukocyte antigen (HLA) class II gene. Blood samples were obtained from 49 patients with gelatin allergy and specific IgE to gelatin. DNA-based HLA class II typing was performed to determine the DRB1, DQB1 and DPB1 alleles. Genotype frequencies were compared with those found in 240 unrelated controls. The frequency of DQB1*0303 (55.1%) was significantly higher in the patients than in the control subjects (32.1%). The frequency of DPB1*0402 was also significantly higher in the patients (32.7%) than in the control subjects (15.4%). On the other hand, the frequency of subjects carrying DRB1*15 (DRB1*1501 and DRB1*1502) was significantly lower among the patients group (18.4%) than among the controls (40.8%). We found that DQB1*0303 and DPB1*0402 were positively associated with the IgE response for gelatin, while DRB1*15 was negatively associated with it.

Child↗

Molecular genetic analysis of the Am phenotype of the ABO blood group system.

BACKGROUND AND OBJECTIVES: Many sequences of variants in the ABO blood group system have been analysed, but genetic information is not available on the rare Am phenotype blood group. We isolated the Am phenotype in one family and performed molecular analysis on this allele. MATERIALS AND METHODS: Exons 6 and 7 of the ABO gene were analysed using genomic DNAs from members of one family containing Am phenotype individuals via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. RESULTS: In the Am allele, two single base substitutions were detected compared with the A101 allele. Both were C --> T mutations at nucleotide positions 467 and 761. PCR-RFLP using the AccI restriction enzyme was performed to detect the Am allele in 214 samples that had already been determined as type A or O by serological tests, but no sample was found to contain an Am allele. CONCLUSIONS: In this study a new allele with a single-base substitution at nucleotide position 761 was identified in the Am phenotype. We designated this new allele as A112 (according to the guidelines for human gene nomenclature) and determined that PCR-RFLP analysis using the AccI restriction enzyme will be useful for detecting this allele.

ABO Blood-Group System↗

Acquired periungual fibrokeratoma with accessory germinal matrix.

Five cases of acquired periungual fibrokeratoma involving the proximal nail fold were treated surgically. Clinically, all five patients regained normal nail contours postoperatively, but one patient developed a local recurrence 1 year after operation. Histologically, an accessory germinal matrix was observed at the distal end of the lesion in all five cases. Change in pressure around the lesion seemed to have induced the formation of this accessory germinal matrix.

Adult↗

The inorganic and organic characters for predicting bioconcentration on wide variety of chemicals in fish.

The applicability of Fujita's inorganic (i) and organic (o) characters as descriptors for predicting bioconcentration factor (BCF) in fish was investigated with a wide variety of organic chemicals. Among 612 BCF data recently released by National Institute of Technology and Evaluation (NITE), the values for the chemicals with a molecular weight of less than 600 and the 1-octanol/water partition coefficient (log P) of less than six were extracted and analyzed. By applying theoretically derived model equation, a good relationship between these BCF and each Fujita's sigma i: sigma o was established. Statistical analyses and model validations revealed that the estimations of our approach were very excellent. More precise predictions were attained than those by using other published models, especially, for chemicals such as disperse dye having hetero atoms.

Animals↗

Complete, long-lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian herpesvirus vector expressing VP2 antigens.

Marek's disease herpesvirus is a vaccine vector of great promise for chickens; however, complete protection against foreign infectious diseases has not been achieved. In this study, two herpesvirus of turkey recombinants (rHVTs) expressing large amounts of infectious bursal disease virus (IBDV) VP2 antigen under the control of a human cytomegalovirus (CMV) promoter or CMV/beta-actin chimera promoter (Pec promoter) (rHVT-cmvVP2 and rHVT-pecVP2) were constructed. rHVT-pecVP2, which expressed the VP2 antigen approximately four times more than did rHVT-cmvVP2 in vitro, induced complete protection against a lethal IBDV challenge in chickens, whereas rHVT-cmvVP2 induced 58% protection. All of the chickens vaccinated with rHVT-pecVP2 had a protective level of antibodies to the VP2 antigen at the time of challenge, whereas only 42 and 67% of chickens vaccinated with rHVT-cmvVP2 or the conventional live IBDV vaccine, respectively, had the antibodies. The antibody level of chickens vaccinated with rHVT-pecVP2 increased for 16 weeks, and the peak antibody level persisted throughout the experiment. The serum antibody titer at 30 weeks of age was about 20 or 65 times higher than that of chickens vaccinated with rHVT-cmvVP2 or the conventional live vaccine, respectively. rHVT-pecVP2, isolated consistently for 30 weeks from the vaccinated chickens, expressed the VP2 antigen after cultivation, and neither nucleotide mutations nor deletion in the VP2 gene was found. These results demonstrate that the amount of VP2 antigen expressed in the HVT vector was correlated with the vaccine efficacy against lethal IBDV challenge, and complete protective immunity that is likely to persist for the life of the chickens was induced.

Animals↗

Effects of maternal exposure to cadmium on pregnancy outcome and breast milk.

OBJECTIVE: The effects of cadmium (Cd) on birth weight have been discussed in the scientific literature. However, investigations on the effects of maternal body burden of Cd on the next generation during pregnancy and lactation have been limited. The relation between maternal exposure to Cd and pregnancy outcome or Cd in breast milk in Japanese mothers was investigated. METHODS: Cd concentrations in urine and colostrum milk samples of 57 mothers were measured by atomic absorption spectrophotometery. The relations between maternal urinary Cd and infant growth, gestational age at birth, and Cd in breast milk were investigated. RESULTS: The rate of perterm deliveries of mothers with higher urinary Cd (> or =2 nmol/mmol creatinine (Cr)) was higher than that of mothers with lower urinary Cd (<2 nmol/mmol Cr). The gestational age was significantly correlated with urinary Cd even after adjustment for maternal age. The height and weight of newborn infants of mothers with higher urinary Cd were significantly lower than those of the newborn infants of mothers with lower urinary Cd, but these decreases were ascribed to early delivery induced by Cd. The Cd in breast milk of mothers with higher urinary Cd was significantly higher than that of mothers with lower urinary Cd. A significant positive correlation was found between maternal urinary Cd and Cd in breast milk. CONCLUSION: Maternal exposure to Cd seems to increase early delivery, which leads to a lower birth weight. Also, the Cd is transferred in part to the next generation through breast milk after birth.

Adult↗

Mapping brain region activity during chewing: a functional magnetic resonance imaging study.

Mastication has been suggested to increase neuronal activities in various regions of the human brain. However, because of technical difficulties, the fine anatomical and physiological regions linked to mastication have not been fully elucidated. Using functional magnetic resonance imaging during cycles of rhythmic gum-chewing and no chewing, we therefore examined the interaction between chewing and brain regional activity in 17 subjects (aged 20-31 years). In all subjects, chewing resulted in a bilateral increase in blood oxygenation level-dependent (BOLD) signals in the sensorimotor cortex, supplementary motor area, insula, thalamus, and cerebellum. In addition, in the first three regions, chewing of moderately hard gum produced stronger BOLD signals than the chewing of hard gum. However, the signal was higher in the cerebellum and not significant in the thalamus, respectively. These results suggest that chewing causes regional increases in brain neuronal activities which are related to biting force.

Adult↗

Analysis of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid from patients with osteoarthritis and rheumatoid arthritis.

We have measured the concentration of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid (SF) from the knees of 49 patients with osteoarthritis (OA) and 79 with rheumatoid arthritis (RA) in order to investigate the correlation between the type of joint disease and level of CD-RAP. The mean concentration of CD-RAP in synovial fluid was significantly higher in OA than in RA. The level of CD-RAP in the group of patients with mild OA was significantly higher than in the moderate or severe groups and that in the group with mild RA was also significantly higher than in the other RA groups and decreased with progression of the disease. Immunohistochemical studies showed expression of CD-RAP in the cytoplasm of chondrocytes in newly-formed fibrocartilage. Since CD-RAP is mainly produced in young and proliferating chondrocytes, our results suggest that the level of CD-RAP in synovial fluid reflects remodelling of articular cartilage and may be used as a marker to estimate objectively the restorative reaction of chondrocytes.

Aged↗

Percutaneous transluminal mitral valvuloplasty improves cardiopulmonary baroreflex sensitivity in patients with mitral stenosis.

Patients with heart failure frequently have increased sympathetic tone, which could result in part from impairment of the inhibitory influence of cardiopulmonary baroreflexes. Percutaneous transluminal mitral valvuloplasty (PTMV) provides a unique model for evaluating functional changes in cardiopulmonary baroreflexes without open-heart surgical manipulation. We examined the effects of PTMV on cardiopulmonary baroreflexes and sympathetic nerve activity in 10 patients with mitral stenosis. We measured muscle sympathetic nerve activity using microneurography. Cardiopulmonary baroreflex provocation was performed by applying a lower body negative pressure of -10 mm Hg, and its sensitivity was determined by dividing the percent change in muscle sympathetic nerve activity by the change in central venous pressure. Response to isometric exercise was assessed by handgrip at 30% of maximal voluntary contraction for 3 min. PTMV significantly increased mitral valve area and cardiac index and decreased mean left atrial pressure. PTMV significantly decreased burst rate from 25.1+/-2.5 to 15.6+/-2.6 bursts/min (p < 0.01) and burst incidence from 37.1+/-3.7 to 23.6+/-3.3 bursts/100 heart beats (p < 0.01). After PTMV, cardiopulmonary baroreflex sensitivities measured using burst rate and burst incidence were -39.9+/-4.9%/mm Hg and -38.7+/-6.2%/mm Hg, respectively, which were significantly steeper than those before PTMV (-9.2+/-1.1%/mm Hg and -8.4+/-1.1%/mm Hg; p < 0.01). There were significant correlations between muscle sympathetic nerve activity at rest and cardiopulmonary baroreflex sensitivity. PTMV did not affect muscle sympathetic responses to handgrip exercise. These results suggest that patients with mitral stenosis have baseline sympathetic nerve activation, which could result in part from impaired cardiopulmonary baroreflexes.

Adult↗

Novel marine-derived halogen-containing gramine analogues induce vasorelaxation in isolated rat aorta.

We examined the effects of 2,5,6-tribromo-1-methylgramine (TBG), isolated from bryozoan, and its derivative, 5,6-dibromo-1,2-dimethylgramine (DBG), on the contraction of rat aorta. TBG and DBG decreased the high-K(+)-induced increase in muscle contraction and cytosolic Ca(2+) level ([Ca(2+)](i)), respectively. The inhibitory effects of TBG and DBG on high-K(+)-induced contraction were antagonized by increasing the external Ca(2+) concentration or by 1,4-dihydro2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]pyridine-3-carboxylic acid (Bay k8644). The high-K(+)-induced increase of Mn(2+) influx was completely blocked by 10 microM TBG or 10 microM DBG. In the Ca(2+)-free solution, 30 microM TBG or 30 microM DBG inhibited the phenylephrine-induced transient increase in [Ca(2+)](i) and muscle tension, while scarcely affecting caffeine-induced transient changes. TBG and DBG significantly increased the cyclic AMP content at 30 microM, but not at 10 microM. These results suggest that TBG and DBG inhibit the smooth muscle contraction by inhibiting Ca(2+) entry, and at higher concentrations, the increase in intracellular cyclic AMP content also contributes to their inhibitory effect.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Revisiting [3 + 3] route to 1,3-cyclohexanedione frameworks: hidden aspect of thermodynamically controlled enolates.

We have revisited the traditional consecutive Michael-Claisen [3 + 3] process (MC-[3 + 3]) promising the synthesis of a cyclohexane-1,3-dione derivatives from nonactivated simple ketones and enoates and evaluated its potential in modern organic synthesis. Twenty to thirty examples were demonstrated to be effective. The reactions exhibited remarkable regioselectivity with the Michael addition proceeding through nucleophilic attack by the more hindered site of the ketones without exception. The subsequent Claisen condensation resulted in the formation of carbon-carbon bonds between less hindered site of the ketones and acyl carbon of the enoates. The MC-[3 + 3] process described is useful for the synthesis of Taxol A-ring synthons in multigram quantities and for the synthesis of other six-membered carbocyclic compounds. A number of control experiments have been conducted to provide strong support for the mechanism of this MC-[3 + 3].

Journal Article↗

Expression of a novel member of the ATP1G1/PLM/MAT8 family, phospholemman-like protein (PLP) gene, in the developmental process of mouse cerebellum.

We have identified a new member of the ATP1G1/PLM/MAT8 family, named phospholemman-like protein (PLP), from a mouse cerebellum cDNA library. The family consists of small transmembrane proteins that modulate the activities of some ion channels. The deduced amino acid sequence of PLP consists of 93 residues that contain the ATP1G1/PLM/MAT8 motif and a single transmembrane domain, and is most similar to the sequence of mouse phospholemman. In situ hybridization analysis showed that the PLP gene is highly expressed in cerebellar granule cells. PLP expression is elevated in the postnatal developing cerebellum. Thus, it may be implicated in the proliferation, differentiation, and axon elongation of granule cells as they mature and migrate to the internal granule layer.

Amino Acid Sequence↗

Glycolipid composition in bladder tumor: a crucial role of GM3 ganglioside in tumor invasion.

Glycolipids were extracted from primary bladder tumors of 14 patients and 2 normal counterparts. Their expression pattern was assessed by thin-layer chromatography (TLC). The most remarkable change was massive accumulation of GM3 in superficial bladder tumors compared with invasive tumors. This change was also confirmed by immunohistochemistry using anti-GM3 monoclonal antibody. The activities of glycosyltransferases responsible for GM3 synthesis (GM3 synthase, Gb3 synthase and GD3 synthase) were consistent with upregulated expression of GM3 in superficial tumors. It was suggested that the marked GM3 accumulation in superficial tumors was caused not only by upregulated GM3 synthase but also by downregulated activities of Gb3 and GD3 synthase. Histopathologic examination revealed an inverse correlation of the amount of GM3 expressed with invasive potential. Exogenously supplemented GM3 suppressed invasion potential in human bladder tumor cell lines (T-24, KK-47). These results indicate that the amount of GM3 expressed may serve as an indicator of the invasion potential of bladder tumor. Furthermore, new antiinvasion therapeutics may be possible by administration of GM3.

Aged↗