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Biomedical subjects

S Sakurai

Publications and source records attributed to S Sakurai.

At least 91 records · Page 5Linked to original sources

[A case of sacral meningeal cyst with Marfan syndrome].

A rare case of sacral meningeal cyst Marfan syndrome is reported. A 40-year-old male who had a past history of Marfan syndrome was admitted to Tokyo Metropolitan Ebara Hospital due to sensory disturbance in the right S1-2 nerve root area on October 1998. On admission, neurological deficits were sensory disturbance and decrease right Achilles reflex. Plain sacral X-ray was normal. Magnetic resonance imaging revealed a cystic mass in the intrasacral space. MR myelography showed the cyst followed the thecal sac. Signal intensity of the cystic mass was the same as the cerebrospinal fluid. In the prone position, laminectomy of the sacrum was carried out. The neck of the meningeal cyst was ligated with the help of an aneurysmal needle. The patient's sensory disturbance disappeared postoperatively. As MRI becomes more frequently used in Marfan syndrome, it is important to keep the presence of such an entity in mind. MR myelography made it easy to diagnose the meningeal cyst.

Adult↗

[Effect of exercise therapy on oxygen consumption in patients with chronic heart failure].

The effect of exercise training on delta Vo2/delta WR was studied in 12 patients(11 men, one woman, mean age 62 +/- 9 yr)with chronic heart failure(old myocardial infarction, dilated cardiomyopathy, patients after coronary arterial bypass graft surgery and patients after aortic valve replacement). Cardiopulmonary exercise testing was performed to decide the exercise tolerance and assess the delta Vo2/delta WR. Patients underwent physical training at the anaerobic threshold for 3 months. Cardiopulmonary exercise testing was performed after the second week and after the third month. The anaerobic threshold increased at the third month compared with before exercise testing and the second week(p < 0.05, respectively) (before exercise testing: 13.6 +/- 2.0 ml/min/kg, the second week: 14.7 +/- 2.5 ml/min/kg, the third month: 16.2 +/- 2.1 ml/min/kg). The delta Vo2/delta WR increased at the second week compared with before exercise testing(before exercise testing: 8.9 +/- 1.9 ml/min/W, the second week: 10.6 +/- 1.9 ml/min/W, p < 0.05), but significantly decreased at the third month compared with the second week(the third month: 9.4 +/- 1.7 ml/min/W, p < 0.05). Serial increase of the anaerobic threshold and the peak Vo2/heart rate suggests that the exercise tolerance and cardiac function of the patients improved significantly. The increase of the delta Vo2/delta WR after the first 2 weeks seemed to depend on the luxury blood supply to both working and non-working muscles. The decrease of delta Vo2/delta WR at the third month may be due to the redistribution of the blood flow to the working muscles.

Chronic Disease↗

Telomerase activity in gastrointestinal stromal tumors.

BACKGROUND: Telomerase activity has been observed in 80-90% of carcinomas derived from various organs. However, to the authors' knowledge this report is the first assessment of telomerase activity in gastrointestinal stromal tumors (GISTs). METHODS: Telomerase activity was analyzed by the telomerase repeat amplification protocol assay in 29 tumors from 26 patients (23 primary tumors from 22 patients, 1 pair of primary and metastatic tumors from 1 patient, and 4 metastatic tumors from 3 patients). Phenotypes, tumor cell proliferation, and overexpression of p53 protein were evaluated immunohistochemically. RESULTS: Seven of 24 primary tumors (29%) and 5 of 5 metastatic tumors (100%) showed telomerase activity. Telomerase activity positive (+) GISTs were significantly larger (P < 0.05) and showed a significantly higher rate of proliferation than telomerase activity negative (-) tumors (P < 0.0001). All telomerase activity (+) GISTs were classified histologically as high risk tumors. Conversely, 15 of the 17 telomerase (-) GISTs were classified histologically as low risk tumors (P < 0.0001). With regard to p53 immunoreactivity, two and seven telomerase activity (+) tumors showed diffuse and sporadic positivity, respectively, whereas only five telomerase activity (-) tumors showed only focal or sporadic positivity. Telomerase activity was correlated significantly with poor prognosis (P < 0.05) in the patients in whom the primary GISTs were evaluated (n = 23). CONCLUSIONS: Telomerase activity may be a useful marker for evaluating the malignant potential of GIST. A distinct subgroup of GISTs is a target for therapy with a telomerase inhibitor.

Adult↗

Changes in T cell subpopulations in lead workers.

To investigate the effects of lead on the human immune system, we analyzed T cell subpopulations and B (CD19+) cells in peripheral blood in 71 male lead workers. They were engaged in manufacturing lead stearate in a chemical factory, aged 20 to 74 (mean 48) years. Their blood lead concentrations (PbB) were between 7 and 50 (mean 19) micrograms/dl. The control group consisted of 28 "healthy" male volunteers without a history of occupational exposure to lead or other hazardous substances, aged 33 to 67 (mean 55) years. In comparison with the controls, a significant reduction in the number of CD3+CD45RO+ (memory T) cells and a significant expansion in the percentage of CD8+ cells in the lead workers were found. There was a significant positive correlation between the percentage of CD3+CD45RA+ (naive T) cells and PbB in the lead workers. It is suggested that CD45RO+ memory T cells may be most susceptible to the effects of lead on T cell subpopulations.

Adult↗

A novel member of the bombyxin gene family: structure and expression of bombyxin G1 gene, an insulin-related peptide gene of the silkmoth Bombyx mori.

Bombyxin G1 gene, a novel insulin-related peptide gene of the silkmoth Bombyx mori, has been identified. The G1 gene encodes a precursor peptide which shows 41-56% and 28% sequence identities with preprobombyxins previously characterized and human preproinsulin, respectively. The G1 gene forms a pair with bombyxin C2 gene with opposite transcriptional orientation in a bombyxin gene cluster. The bombyxin G1 mRNA in Bombyx brain was shown to locate in four pairs of medial neurosecretory cells.

Amino Acid Sequence↗

Survival of patient with late onset hepatic failure by living-related liver transplantation from maternal donor with incompatible blood type.

A 14-year-old girl with blood type B with late onset hepatic failure (LOHF) of unknown cause has survived through living-related liver transplantation (LRLT). No hepatitis virus, including HAV, HBV, HCV, and HGV, was positive at the onset of LOHF. Autoimmune hepatitis was thought to be the cause because of positive results for serum anti-nuclear antibody at 80 times dilution and elevated gamma-globulin, but treatment with glucocorticoid did not suppress the progressive hepatic failure. Supportive therapy, including pulse therapy with 1g methylprednisolone for 3 days, ursodesoxycholic acid, branched-chain amino acid, and azathioprine did not resolve the hepatic failure. She was treated by repeated plasmapheresis and plasma absorption for 10 months, and then received the left lobe of her mother's liver. (Her mother's blood type was AB). The patient had been well, being treated with tacrolimus and prednisolone, although the serum titer of anti-blood type B antibody was high just after LRLT and mild liver dysfunction continued for more than 3 years after LRLT. Follow-up biopsy 3 years after LRLT revealed chronic hepatitis and progression to liver cirrhosis. Re-transplantation is now under consideration; the patient is now aged 19 years.

ABO Blood-Group System↗

Hemolymph ecdysteroid titer and ecdysteroid-dependent developmental events in the last-larval stadium of the silkworm, Bombyx mori: role of low ecdysteroid titer in larval-pupal metamorphosis and a reappraisal of the head critical period.

The endocrine regulation of larval-pupal metamorphosis was studied in the silkworm, Bombyx mori, by measuring the following changes: hemolymph ecdysteroid titer, the secretory activity of prothoracic glands and the responsiveness of larvae to ecdysteroids and prothoracicotropic hormone (PTTH), with regard to developmental events such as the occurrence of spinneret pigmentation, initiation of cocoon spinning and onset of wandering stage as indicated by gut purge. These measurements were concentrated especially on the time before and after the head critical period (HCP) which falls 3-4 days before the gut purge ([Sakurai, 1984]). A small increase in the hemolymph ecdysteroid titer was first found during the HCP, and then the titer increased with daily fluctuations. Small but significant titer peaks were found prior to the occurrence of both spinneret pigmentation and gut purge, indicating that an individual titer peak could possess a specific role in development. Responsiveness of larvae to exogenous 20-hydroxyecdysone (20E) after the HCP was markedly higher than that before the HCP. The sensitivity of the prothoracic gland to PTTH also changed during the HCP. The results thus showed that the HCP is not the period after which an additional PTTH release is not required for the developmental events occurring on schedule, but rather it is the period during which complex events occur not only in the endocrine glands but also in the peripheral tissues. In addition, various developmental phenomena before gut purge are brought about by the hemolymph ecdysteroid whose concentration gradually increased with daily fluctuations, and these precise changes in the titer appeared to be important for the sequential occurrence of developmental events in the larval-pupal metamorphosis.

Journal Article↗

Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin.

We investigated the effects of recombinant human BMP-2 (rhBMP-2) on differentiation of cells isolated from human bone, muscle, and skin. Cells isolated from bones of six patients (HBM-1 to HBM-6), muscle from five patients (HM-1 to HM-5), and skin from three patients (HF-1 to HF-3) were used. rhBMP-2 had no effects on proliferation of two HBM cells, but had a stimulatory effect on three HM cell samples. rhBMP-2 stimulated both alkaline phosphatase (ALP) activity in all HBM cells and parathyroid hormone (PTH)-dependent cAMP production in three of the four HBM cell samples, although the magnitudes of these stimulatory effects differed among the cells tested. Although none of the HBM cells examined produced detectable amounts of osteocalcin in the absence of 1,25-(OH)2vitamin D3, they synthesized measurable amounts of osteocalcin in its presence. rhBMP-2 inhibited 1,25-(OH)2vitamin D3-dependent osteocalcin production in all of the HBM cell samples. Transplantation of HBM-6 cells with rhBMP-2 using diffusion chambers into the peritoneal cavity of athymic mice induced formation of cartilage and bone in the diffusion chambers, but neither cartilage nor bone was formed in chambers transplanted without rhBMP-2. rhBMP-2 also stimulated ALP activity in all of the HM and HF cell samples examined and PTH-dependent cAMP production in three of four HM cell samples. rhBMP-2 induced no osteocalcin production in any of the HM or HF cells in the presence of 1,25-(OH)2vitamin D3. rhBMP-2 markedly inhibited myotube formation by all of the HM cell samples. Transplantation of HM-4 cells with rhBMP-2, using diffusion chambers, into athymic mice induced ALP-positive cells in the chambers, but neither cartilage nor bone was observed. These results suggest that rhBMP-2 is a potent stimulator of osteoblast differentiation and bone formation in human cells.

Alkaline Phosphatase↗

Oestradiol regulation of the components of the plasminogen-plasmin system in MDA-MB-231 human breast cancer cells stably expressing the oestrogen receptor.

To understand the hormonal regulation of the components of the plasminogen-plasmin system in human breast cancer, we examined the oestradiol (E2) regulation of plasminogen activators (PAs), namely urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) and uPA receptor (uPAR), in our model system. We used stable transfectants of the MDA-MB-231 human breast cancer cells that express either the wild-type (S30 cells) or the mutant 351asp-->tyr oestrogen receptor (ER) (BC-2 cells). Northern blot analysis showed that there was a concentration-dependent down-regulation of uPA, tPA and PAI-1 mRNAs by E2. In contrast, uPAR mRNA was not modulated by E2. The pure anti-oestrogen ICI 182,780 was able to block E2 action, indicating that the regulation of these genes is ER mediated. The E2 also inhibited the expression and secretion of uPA, tPA and PAI-1 proteins as determined by enzyme-linked immunosorbent assay (ELISA) in cell extracts (CEs) and conditioned media (CM). Zymography of the CM confirmed the inhibitory effect of E2 on uPA activity. Thus, we now report the regulation of uPA, PAI-1 and tPA by E2 in both mRNA and protein levels in ER transfectants. The association between down-regulation of the uPA by E2 and known E2-mediated growth inhibition of these cells was also explored. Our findings indicate that down-regulation of uPA by E2 is an upstream event of inhibitory effects of E2 on growth of these cells as the addition of exogenous uPA did not block the growth inhibition by E2.

Breast Neoplasms↗

Changes of telomere length in children after hematopoietic stem cell transplantation.

Telomeres are responsible for keeping the stability not only of chromosomes but also of genes. To investigate the effect of hematopoietic stem cell transplantation (HSCT) on telomeres, we studied telomere length in the peripheral blood mononuclear cells of 31 children who received HSCT. In the auto-HSCT groups telomere length ranged from 8.6 to 12.0 kb and in the allo-HSCT groups from 8.4 to 12.0 kb. Comparison of the telomere length between before and after auto-HSCT showed shorting up to 1.0 kb. Moreover, comparison between donors and recipients in allo-HSCT revealed that telomeres of recipients were up to 1.0 kb shorter than those of the donors. Patients who received allo-HSCT from donors older than 18 years had significantly shorter telomeres than those transplanted from donors under 18 years old (P < 0.05), indicating that donor age is an important factor for recipient's telomere length. These findings suggest that the effects which might be induced by shortening of telomeres in recipients are within the biologically tolerable range. However, if hematopoietic stem cells from elderly donors are transplanted into younger patients, the telomere length may become too short for acceptable lifetime risks of genetic instability in the recipient.

Adolescent↗

Serum substances that interfere with thyroid hormone assays in patients with chronic renal failure.

OBJECTIVE: Serum thyroid hormone concentrations in patients with chronic renal failure are usually low, despite normal serum TSH levels. We investigated the effect on thyroid hormone assays of serum dialysable organic acids that are elevated in uraemic patients. PATIENTS: Serum samples from 42 patients with chronic renal failure who were receiving haemodialysis and 37 sex- and age-matched healthy subjects were examined. DESIGN AND MEASUREMENTS: Serum thyroid hormone concentrations were measured with an analogue radioimmunoassay (RIA), a labelled antibody assay, and an equilibrium dialysis/RIA method. Serum concentrations of organic acids were determined with high performance liquid chromatography. RESULTS: Serum thyroid hormone levels determined by an analogue RIA and a labelled antibody assay in uraemic patients increased, and serum concentrations of organic acids decreased following haemodialysis. A significant association existed between serum free T3 (FT3) levels determined by an analogue RIA and serum concentrations of indoxyl sulphate (IS) prior to dialysis. There was also a significant association between serum free T4 (FT4) levels determined by an analogue RIA and serum concentration of IS and hippuric acid (HA) prior to dialysis. There was a significant association between the changes of serum concentrations of indole acetic acid (IAA) and FT4 concentrations prior to and following haemodialysis when determined by an analogue RIA. Serum FT3 and FT4 levels significantly decreased after the addition of IS to serum from healthy subjects when determined by an analogue RIA but not by a labelled antibody assay. Serum FT4 levels, but not FT3 levels, decreased after addition of IAA when determined by an analogue RIA. Serum FT4 concentrations determined by an equilibrium dialysis/RIA were significantly higher than those determined by the other two methods. The addition of IS, IAA, and HA to serum samples from healthy subjects significantly increased FT4 concentrations when determined by an equilibrium dialysis/RIA method. CONCLUSIONS: Increased serum levels of indoxyl sulphate, indole acetic acid and hippuric acid in sera of uraemic patients may interfere with thyroid hormone measurements when an analogue radioimmunoassay is used. In contrast, there was little Interference with a labelled antibody assay. Dialysable organic acids may also interfere with thyroid hormone assays determined by an equilibrium dialysis/radioimmunoassay method.

Aged↗

New evidence that the Tyr-157 and Tyr-159 residues of staphylococcal exfoliative toxin B are essential for its toxicity.

To determine the active site of exfoliative toxin B (sETB) of Staphylococcus aureus, the etb gene was cloned from an S. aureus SU strain obtained from a patient with impetigo. We prepared a frame shift mutant protein from a recombinant plasmid with a BglII linker inserted into the Tyr-155 codon of the ETB gene (pETB/BglIIL). The recombinant mutant protein (ETB/BglIIL) obtained from Escherichia coli containing pETB/BgIIIL showed no toxicity in neonatal mice and no agglutination activity. The 20-kDa ETB/BglIIL contained 185 amino acid residues. Site-directed mutagenesis was used to introduce mutations at either Tyr-155, Tyr-157, Tyr-159, or Tyr-162. Substitution of any of the Tyr residues decreased exfoliative activity compared with that of native sETB (4,000 EU/ml). Substitution of Tyr-155 with a Phe (ETBYN155) decreased activity 5-fold (800 EU/ml). Substitution of Tyr-157 with Leu (ETB/Y157) decreased activity 80-fold (50 EU/ml) and decreased agglutination titer 5-fold compared with that of native sETB (400,000). Substitution of Tyr-159 with Leu (ETB/Y159)decreased activity 4-fold (1,000 EU/ml). When both Tyr-157 and Tyr-159 were mutated (ETB/Y157-159), both toxicity and antigenicity were completely lost. On an immunodiffusion test, ETBNY157 showed a faint precipitation line, but ETB/BglIIL and ETB/Y157-159 had no activity, showing that the Tyr-157 and Tyr-159 residues are essential for the toxicity and antigenicity of ETB.

Amino Acid Sequence↗

Inhibition of tumor cell growth by murine splenic adherent cells stimulated with IFN-gamma.

We have previously reported that the growth of lymphocytes and tumor cells with lymphocyte lineage was strongly inhibited by a part of cloned macrophage hybridomas. This growth inhibition was accomplished by cell-to-cell contact and found to be attributed to lipid-like molecule(s) in a macrophage hybridoma cell membrane fraction. Instead of macrophage hybridomas, in the present study we utilized splenic adherent cells (SACs) that had been stimulated with IFN-gamma to see whether they inhibited tumor cell growth or not. The results demonstrated that IFN-gamma-stimulated but not unstimulated SACs showed a significant growth inhibition of BW-5147 tumor cells. This growth inhibition was not mainly mediated by prostaglandin E2 secreted from macrophages, since the inhibition was not reduced in the presence of indomethacin. Furthermore, as was reported previously in the case of macrophage hybridomas, the inhibitory activity resides in a lipid fraction of IFN-gamma-stimulated SAC membrane.

Animals↗

Health effects of indoor fluoride pollution from coal burning in China.

The combustion of high fluoride-content coal as an energy resource for heating, cooking, and food drying is a major exhaust emission source of suspended particulate matter and fluoride. High concentrations of these pollutants have been observed in indoor air of coal-burning families in some rural areas in China. Because airborne fluoride has serious toxicological properties, fluoride pollution in indoor air and the prevalence of fluorosis have been analyzed in a fluorosis area and a healthy nonfluorosis area in China and in a rural area in Japan. For human health, fluoride in indoor air has not only been directly inhaled by residents but also has been absorbed in stored food such as corn, chilies, and potatoes. In the fluorosis area in China, concentrations of urinary fluoride in the residents have been much higher than in the nonfluorosis area in China and in the rural area in Japan. In the fluorosis area, almost all elementary and junior high school students 10-15 years of age had dental fluorosis. Osteosclerosis in the skeletal fluorosis patients was very serious. Urinary deoxypyridinoline in rural residents in China was much higher than in rural residents in Japan. Data suggest that bone resorption was extremely stimulated in the residents in China and that fluoride may stimulate both bone resorption and bone formation. Because indoor fluoride from combustion of coal is easily absorbed in stored food and because food consumption is a main source of fluoride exposure, it is necessary to reduce airborne fluoride and food contamination to prevent serious fluorosis in China.

Adolescent↗

Increase in the helper inducer (CD4+CD29+) T lymphocytes in smokers.

Previously, we reported an increase in the number of CD4+ T lymphocytes in the peripheral blood of smokers. In the present study, subpopulations of CD4+ T lymphocytes together with CD8+ T lymphocytes, total (CD3+) T lymphocytes, B (CD19+) lymphocytes, natural killer (CD16+) cells and total lymphocytes were examined by two-color staining using anti-2H4 (CD45RA) and anti-4B4 (CD29) monoclonal antibodies in 8 male smokers and 22 age-matched male non-smokers. The number of CD4+CD29+ T lymphocytes in smokers was significantly higher than that in non-smokers. The total number of CD4+ T lymphocytes in smokers was also significantly higher. No significant differences in CD8+ T, CD19+ B lymphocytes and CD16+ NK cells were found between smokers and non-smokers. Thus, it is suggested that the increase in the number of CD4+CD29+ (helper inducer) T lymphocytes is responsible for the increase in total CD4+ T lymphocytes in smokers.

Adult↗

Ovalbumin coupled either with murine red blood cells or liposome induces IgG but not IgE antibody production.

Ovalbumin (OVA) was coupled with murine red blood cells (MRBC) using glutaraldehyde. The OVA-MRBC conjugate induced anti-OVA IgG antibody in mice at almost the same level as OVA in alum. However, no IgE antibody production specific for OVA was observed in OVA-MRBC-injected mice. A significant increase in IGG2a production was obtained with OVA-MRBC immunization, whereas the production of IgG1 predominated in OVA in alum immunization. Am OVA-liposome conjugate induced IgE-specific unresponsiveness in mice in the same manner as OVA-MRBC. Similar results were obtained when antigens other than OVA, such as tetanus toxoid or diphtheria toxoid, were coupled to liposome. These results show the potential of antigen-liposome conjugates for the development of vaccine that induces sufficient IgG antibody production without IgE synthesis.

Alum Compounds↗

[Effects of antihypertensive treatment on the thickening of the basal portion of the interventricular septum in essential hypertension].

Previous echocardiographic studies have indicated that the basal portion of interventricular septum is locally thickened in many patients with essential hypertension. This retrospective study investigated whether this localized thickening is decreased by antihypertensive treatment. Twenty-four patients with mild essential hypertension (15 males, 9 females, mean [+/- SD] 55 +/- 9 years) were selected who had local thickening at the basal portion of interventricular septum (> or = 11 mm) on echocardiograms recorded within 3 months after the first visit and were followed up by echocardiography 6 months or more after the start of antihypertensive treatment. Interventricular septal wall thickness at the mid portion (IVST), posterior wall thickness (PWT), left ventricular mass index (LVMI), aorto-septal angle, blood flow velocity in left ventricular outflow tract, and the thickness of the basal portion of interventricular septum (septal wall maximum thickness within 1.5 cm apex side from the joint of interventricular septum and aorta in the long-axis view of B-mode echocardiograms) were measured. Blood pressure was significantly decreased from 152.7 +/- 8.7/93.1 +/- 8.0 mmHg to 140.0 +/- 8.2/86.6 +/- 8.2 mmHg by treatment (p < 0.0001). The thickness of the basal interventricular septum was significantly reduced by treatment from 12.3 +/- 1.7 mm to 10.3 +/- 1.4 mm (p < 0.0001). Mean IVST, PWT and LVMI were slightly reduced by treatment, but the differences were not statistically significant. These results suggest that the thickening of basal interventricular septum is induced by high blood pressure, and the measurement of the thickness of basal interventricular septum might be a useful tool to estimate and monitor the effect of antihypertensive treatment in patients with mild essential hypertension.

Adult↗