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Biomedical subjects

T Sano

Publications and source records attributed to T Sano.

At least 217 records · Page 12Linked to original sources

Phosphate as a limiting factor for the cell division of tobacco BY-2 cells.

The re-addition of phosphate to tobacco BY-2 cells deprived of phosphate for 3 d induced cells to semi-synchronously re-enter the cell cycle from a static state. Though the addition of auxin to auxin-starved tobacco BY-2 cells also induced cell division (Ishida et al. 1993), some major differences were observed between these two systems. BY-2 cells lost the ability to re-enter the cell cycle after prolonged periods of auxin deprivation, but in contrast retained this ability after longer periods in the absence of phosphate. By differential cDNA screening we identified a phosphate-induced gene phi-1. phi-1 was rapidly induced by the addition of phosphate with transcript levels starting to decrease by the start of DNA synthesis. phi-1 does not share any significant homology with any gene with known functions over its full length. However, the N-terminus shared some homology with plasma membrane ATPases suggesting that it may be involved in some process of phosphorylation. Immunolocalization of the phi-1 gene product revealed that it rapidly accumulated in the cytoplasm prior to the start of plastid and nuclear DNA synthesis. These results are discussed in relation to the role of phosphate in inducing plant cell division.

Amino Acid Sequence↗

Intravascular stenting of systemic venous baffle stenosis after corrective surgery for double outlet right ventricle with left isomerism.

A 14 year old girl with double outlet right ventricle, left isomerism, and complicated atrial anatomy had undergone corrective surgery with intra-atrial rerouting at 5 years of age. Cardiac catheterisation eight years after the surgery showed that she had two systemic venous baffle stenoses: between the hepatic vein and caval vein, and the caval vein and right atrium. Two Palmaz stents were successfully implanted percutaneously through a long sheath and a balloon catheter. The stenoses were relieved immediately and her symptoms quickly disappeared.

Adolescent↗

Amelioration of acromegaly after pituitary infarction due to gastrointestinal hemorrhage from gastric ulcer.

We report a rare case of acromegaly in which pituitary infarction possibly developed in a GH-producing pituitary adenoma following gastrointestinal bleeding from peptic ulcer. In this case, pituitary infarction resulted in spontaneous remission of acromegaly associated with diabetes mellitus. In addition, detailed histological investigation revealed that clinically silent pituitary apoplexy was mainly an acute ischemic event which occurred recently in a GH-producing adenoma. This event led to massive coagulation necrosis of the tumor and endocrinological improvement.

Acromegaly↗

Infrequent detectable somatic mutations of the RET and glial cell line-derived neurotrophic factor (GDNF) genes in human pituitary adenomas.

RET is a receptor tyrosine kinase expressed in neuroendocrine cells and tumors. RET is activated by a ligand complex comprising glial cell line-derived neurotrophic factor (GDNF) and GDNF receptor-alpha (GDNFR-alpha). Activating mutations of the RET proto-oncogene were found in multiple endocrine neoplasia (MEN) 2 and in sporadic medullary thyroid carcinoma and pheochromocytoma of neuroendocrine origin. Mutations of the RET proto-oncogene and the glial cell line-derived neurotrophic factor (GDNF) gene were examined in human pituitary tumors. No mutations of the RET proto-oncogene including the cysteine-rich region or codon 768 and 918 in the tyrosine kinase domain were detected in 172 human pituitary adenomas either by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) or by PCR-restriction fragment length polymorphism (RFLP). Further, somatic mutations of the GDNF gene in 33 human pituitary adenomas were not detected by PCR-SSCP. One polymorphism of the GDNF gene at codon 145 of TGC or TGT was observed in a prolactinoma. The RET proto-oncogene message was detected in a normal human pituitary gland or 4 of 4 human pituitary adenomas with reverse transcription (RT)-PCR, and in rodent pituitary tumor cell lines with Western blotting. The expression of GDNF gene was detected in 1 of 4 human somatotroph adenomas, 1 of 2 corticotroph adenomas, and 2 of 6 rodent pituitary tumor cell lines with RT-PCR. Based on these, it is concluded that somatic mutations of the RET proto-oncogene or the GDNF gene do not appear to play a major role in the pituitary tumorigenesis in examined tumors.

Adenoma↗

Growth hormone advances spermatogenesis in premature rats treated with gonadotropin-releasing hormone agonist.

To clarify the effect of GH on the development of seminiferous tubules in premature male rats, we investigated whether GH accelerates spermatogenesis under the condition of gonadotropin deprivation. Male Wistar rats aged three weeks were divided into three groups and subjected to administration of either long-acting GnRH agonist (GnRHa) or a combination of GnRHa and rat GH, with normal saline solution as control. After the 4-week treatment, sperm density and motility in the right epididymis were measured and seminiferous tubules of right testes were histologically examined. Sperm density and motility were significantly higher in GnRHa+GH-treated rats than in GnRHa-treated rats. In histological examination, the numbers of germ cells in various stages were increased in GnRHa+GH-treated rats compared with GnRHa-treated rats, with the number of mature spermatid being noticeably higher in GnRHa+GH-treated rats. These results suggest that administration of GH decreases loss of germ cells at various stages of spermatogenesis under the condition of gonadotropin withdrawal.

Analysis of Variance↗

Regional left ventricular motion during early filling phase in patients with right ventricular pressure overload.

Global left ventricular (LV) diastolic function has been reported to be disturbed under conditions of right ventricular pressure overload (RVPO). However, from the standpoint of regional wall motion, only a little information related to the mechanism of LV diastolic dysfunction is available. Eight patients with RVPO and 7 healthy volunteers were investigated using tagged cine magnetic resonance imaging. Regional diastolic fraction (RDF) was determined in 4 segments (anterior, lateral, inferior, and septal) in the mid-ventricular short axis section and in 2 segments (septal and lateral) in the 4-chamber section. A heterogeneity index was obtained from the RDFs of the short axis section. In the RVPO group, in both short axis and 4-chamber sections, the RDF of the septal segment was depressed, and it showed an inverse correlation with the right-to-left ventricular systolic pressure (RV/LV) ratio (r = -0.74, p < 0.05) in the short axis section. In the 4-chamber section, the RDF was lower in the septal segment than in the lateral segment (p < 0.05). The heterogeneity index in the RVPO group was greater than that in the control group (p < 0.01). The index correlated positively with the RV/LV ratio (r = 0.77, p < 0.05). The altered regional diastolic motion results in increased heterogeneity in regional diastolic motion.

Adolescent↗

Underglycosylation of IgA1 hinge plays a certain role for its glomerular deposition in IgA nephropathy.

This study was performed to isolate and investigate the IgA1 that could accumulate in glomeruli (glomerulophilic IgA1). IgA1 was fractionated by the electric charge and the reactivity to Jacalin. Serum IgA1 of IgA nephropathy patients was separated and fractionated using a Jacalin column and subsequent ion-exchange chromatography. The fractions were divided into three groups of relatively cationic (C), neutral (N), and anionic (A). IgA1 was also divided into Jacalin low (L), intermediate (I), and high (H) affinity fractions by serial elution using 25, 100, and 800 mM galactose. The left kidneys of Wistar rats were perfused with 2, 5, or 10 mg of each group of IgA1. The rats were sacrificed 15 min, 30 min, 3 h, or 24 h after the perfusion. The accumulation of each IgA1 in the glomeruli was then observed by immunofluorescence. The IgA1 of the fractions N and H separated by the two methods was definitely accumulated in the rat glomeruli with a similar pattern. The electrophoresis revealed that the macromolecular IgA1 was increased in fraction H compared with other fractions. Therefore, Jacalin high-affinity IgA1(fraction H) was applied on a diethylaminoethyl column and divided into electrically cationic (HC), neutral (HN), and anionic (HA). Only the asialo-Galbeta1,3GalNAc chain was identified in the fraction HN IgA1 by gas-phase hydrazinolysis. Furthermore, the IgA1 fraction was strongly recognized by peanut agglutinin, Vicia Villosa lectins, and antisynthetic hinge peptide antibody. These results indicated that the IgA1 molecules having the underglycosylated hinge glycopeptide played a certain role in the glomerular accumulation of IgA1 in IgA nephropathy.

Animals↗

The zymogen prothrombin stimulates cell locomotion and calcium influx in murine osteosarcoma cells by different mechanism from thrombin.

The coagulation system plays a role in tumor invasion and metastasis. Prothrombin was previously found to stimulate the motility of melanoma cells. We compared the effect of prothrombin and thrombin on cell motility, calcium influx and actin stress filament contraction in highly metastatic osteosarcoma LM8 cells. Prothrombin and thrombin stimulated chemotaxis and chemokinesis of LM8 cells in a dose-dependent manner. Calcium influx was significantly increased after stimulation with thrombin and prothrombin. Thrombin and prothrombin markedly stimulated actin contraction in LM8 cells. Hirudin inhibited the effects of thrombin but not those of prothrombin. Prothrombin appears to stimulate cell locomotion, actin contraction, calcium influx in LM8 cells by different mechanism from thrombin.

Actins↗

[Practice guidelines in western countries].

The concept of clinical practice guidelines was established in the 1960's to reduce medical costs that had been increasing dramatically in the US. To reduce medical expenses without lowering the quality of medical care, thorough control of medical practices was undertaken by rationalization of these practices. Guidelines were started initially for social and economical reasons, but were eventually accepted widely by society for several reasons. First, the concept of patients' autonomy was widely accepted after 1970, which supported full disclosure of information to patients. Second, there was too much information, necessitating ranking by scientific certainty. Third, the risk of litigation for doctors in the USA increased dramatically during these years. Whether a medical practice follows the guidelines or not has become one of the most important issues in medical lawsuits. Fourth, there is a constant demand for the effective use of social resources. Methods for developing clinical practice guidelines are already established in many societies. The first step is an intensive review of relevant articles to generate evidence-based recommendations (EBR). Then, to formulate practice guidelines, these EBR are ratified and modified by clinicians to whom they apply. They are then reviewed by independent experts. After final adjustment of the EBR or guidelines for administrative reasons, they are adopted with a future expiry date. Practice guidelines are not actually adopted in European countries. However, the concept of guidelines is well appreciated and medical practice is based on scientific evidence. In socialistic European countries like Sweden, Denmark or the Netherlands, there is huge pressure to control limited social resources, leading to aggressive efforts to reduce unexplained and inappropriate variations in medical practice.

Evidence-Based Medicine↗

[Treatment of recurrent cancer after surgery for biliary malignancies].

Our strategy for recurrent tumor after surgical resection for biliary malignancies, especially for hilar cholangiocarcinoma, is described. One hundred and thirty-three patients with hilar cholangiocarcinoma underwent curative resection in our department until November, 1998, and recurrent carcinomas have been pointed out in 73 patients (54.9%). The site of recurrence was peritoneum (21 cases), liver (16 cases), pre-caval and retro-duodenal space (15 cases), hepatic hilum (11 cases), lymph node (9 cases), bone (6 cases), sinus tract of percutaneous transhepatic biliary drainage (PTBD) (5 cases) and so on. Surgical resection was applied to recurrent carcinomas after careful evaluation, and 9 patients underwent surgical resection of the recurrent tumor: sinus tract of PTBD in the abdominal and/or chest wall (4 cases), lymph node (2 cases), liver (1 case), hepaticojejunostomy (1 case) and duodenum (1 case). There were three hospital death patients. Other six patients survived for 16 months on an average (11-20 months) after surgery for recurrent tumor. PTBD for recurrent cancer at the hepatic hilum and gastrojejunostomy for local recurrence around the duodenum improved quality of life of patients. Radiation therapy for bone metastasis or local recurrence at the hepatic hilum was sometimes very effective. Effect of systemic or transarterial chemotherapy is still unknown.

Adult↗

[Intraoperative assessment by laser-Doppler skin blood flowmetry of the efficacy of endoscopic thoracic sympathectomy].

We have investigated whether laser-Doppler (L-D) skin blood flowmetry on the finger could be useful for an intraoperative assessment of the efficacy of endoscopic thoracic sympathectomy (ETS) under general anesthesia. Subjects were 5 young adults receiving ETS for palmar hyperhidrosis. ETS was performed with the patients in the semi-sitting position under one lung ventilation. A pair of LDF probes were placed on the palmar side of the both second fingers. Palmar hyperhidrosis disappeared after ETS in all cases, but compensatory hyperhidrosis developed in the back of the body and the thigh. After completion of ETS on one side, the L-D skin blood flow increased to 267.6 +/- 211.1% on the side of ETS, and it increased in 2 other cases and decreased on the contrary in 3 cases on the other side. After ETS on both sides the L-D skin blood flow increased to 265.0 +/- 185.9% on the side of initial ETS and to 211.4 +/- 172.8% on the side of subsequent ETS. The initial EST induced reflex vasoconstriction on the finger of both sides and also on the toe. Spontaneous fluctuation and reflex vasoconstriction of the skin blood flow were still observed, although the periodicity of spontaneous fluctuation between the right and the left finger was lost in some of the cases. An increase in L-D skin blood flow on the side of ongoing ETS is useful for intraoperative assessment of ETS.

Adult↗

Biologic markers in prostatic intraepithelial neoplasia: immunohistochemical and cytogenetic analyses.

OBJECTIVE: We evaluated the biological properties of High-grade prostatic intraepithelial neoplasia (PIN) by immunohistochemistry and fluorescence in situ hybridization (FISH) analysis in relation to normal tissue and carcinoma lesions. MATERIALS AND METHODS: Immunohistochemical staining and FISH were performed on 23 formalin-fixed radical prostatectomy specimens taken from patients with PIN. Assays were performed using MIB-1, chromogranin A (CGA) and an anti-androgen receptor antibody (AR). A centromere probe for chromosome 8 was used to test for aneuploidy. RESULTS: The MIB-1 index of cancerous specimens (16.2 +/- 10.5%) was significantly higher than that of benign (1.9 +/- 1.6%, p < 0.0001) or PIN (4.0 +/- 4.5%, p < 0.0001) specimens. The percentage of CGA positive cells was significantly lower in normal tissue (1.2 +/- 1.8%) than in PIN (3.5 +/- 2.9%, p = 0.012) or carcinoma (5.4 +/- 4.9%, p = 0.005) lesions. Positive staining for AR was consistently observed in the nuclei of both benign and malignant epithelial cells, but positive cytoplasmic staining was also seen in PIN epithelial cells. No significant difference in FISH detected anomalies were found between PIN and carcinoma specimens. CONCLUSIONS: Our studies concerning proliferative activity, NE differentiation and chromosomal anomalies of prostatic specimens support the hypothesis that PIN is a biologically intermediate stage in the pathogenesis of prostatic carcinoma. The cellular distribution of AR was altered in PIN cells, but the role of AR in PIN is not yet clear.

Aged↗

The utility and limitations of an ultrasonic miniprobe in the staging of gastric cancer.

To determine the utility and limitations of an ultrasonic miniprobe (UMP) in the staging of gastric cancer, we evaluated 46 patients who underwent endoscopic ultrasonography (EUS) using an UMP and who were histologically determined to have gastric cancers. In every case, UMP findings were compared with histopathological findings after treatment. The total accuracy of UMP relative to the depth of tumor invasion was 71.7% (33/46 cases). Accuracy with respect to T1-m tumor diagnosis was 75.7% (22/29 cases), and for T1-sm, 76.9% (10/13 cases), but accuracy for T2 tumor diagnosis was low, due to ultrasound attenuation. When the analysis was carried out based on the size of tumor, the accuracy for UMP was 50.0% (9/18 cases) for all tumors over 20 mm and 85.7% (24/28 cases) for all tumors smaller than 20 mm. We conclude that UMP is suitable for investigation of tumor extension when the lesion is superficial and/or small gastric cancers which do not cause ultrasonic attenuation, but not when the tumor is large or located in certain sites, although conventional EUS is useful in some of these cases.

Aged↗

Hexagonal bilayer structuring activity of linker chains of an annelid giant hemoglobin from the polychaete Perinereis aibuhitensis.

Preferential activity of linker chains to clamp submultiples to form hexagonal bilayer (HBL) assembly of the multisubunit hemoglobin (Hb) of the polychaete Perinereis aibuhitensis (approximately 3.4 MDa) was demonstrated. To understand the HBL assembly that should rely on structuring activity of each subunit, reassociation in response to combining isolated subunits was monitored using gel filtration, SDS-PAGE, and transmission electron microscopy. The isolation of each subunit L, T, and M (L, linker chains; T, disulfide-bonded trimer A-b-B; M, monomeric chain a) of Perinereis Hb was made simply by exposing Hb to pH 10.5, where Hb was completely dissociated into its subunits L, T, and M. As a result, it was concluded that (i) subunits T and M have strong affinity to form an intermediate complex, submultiple D, which is a dodecamer of globin chains, 3[a. A-b-B], (ii) addition of subunit L to submultiple D brings about the formation of whole molecule, similarly (iii) addition of subunit M to T+L forms the whole molecule, and (iv) addition of subunit T to M+L brings about the formation of the whole molecule, too. The results obtained lead us to conclude that linkers do function to clamp 12 submultiples D up to a whole molecule at the final step of formation of Perinereis Hb. In summary, linkers appeared to have high affinity for submultiple D, a little affinity for subunit T, but no affinity for subunit M at all. Thus linker chains were demonstrated to preferentially clamp submultiples D together to form the HBL disc of the whole molecule.

Animals↗

Adenoviral transgene expression of MMAC/PTEN in human glioma cells inhibits Akt activation and induces anoikis.

The MMAC/PTEN tumor suppressor gene encodes for a phosphatase that recently has been shown to have phosphotidylinositol phosphatase activity, implicating its possible involvement in phosphatidylinositol 3'-kinase-mediated signaling. To investigate possible alterations in growth factor-mediated signal transduction, an adenovirus containing MMAC/PTEN, Ad-MMAC, previously shown to inhibit growth and tumorigenicity in glioma cells, was used to acutely express the transgene. Human glioma cells infected with Ad-MMAC but not with control adenoviruses exhibited an inhibition of phosphorylation of both activating residues of Akt, Ser-473, and Thr-308, along with Akt's serine/threonine kinase activity, without significantly altering Akt expression. The effects of functional MMAC/PTEN expression were relatively specific, because members of several other growth factor-mediated signaling pathways showed no altered responses. The presence of MMAC/PTEN also inhibited phosphorylation of BAD, although no evidence of apoptosis in the in situ treated cells was observed. However, U251 glioma cells infected with Ad-MMAC were induced to undergo anoikis at a significantly higher rate than U251 cels treated with control viruses or mock infected with media. These results demonstrate that the acute administration of MMAC/PTEN results in the inhibition of Akt-mediated signaling, growth inhibition, and anoikis, implying that loss of MMAC/PTEN increases cellular proliferation and significantly augments a cell's survival potential during cellular processes that are associated with malignancy.

Adenoviridae↗

Left ventricular regional systolic motion in patients with right ventricular pressure overload.

Left ventricular regional systolic motion was investigated in patients with right ventricular pressure overload and 10 controls using tagged cine magnetic resonance imaging. The regional shortening fraction was determined in four segments (septal, lateral, inferior, and anterior) on the short-axis image. An asynchrony index, nonhomogeneity of regional shortening, was calculated. Septal shortening in these patients was depressed, and showed an inverse correlation with the right-to-left ventricular peak pressure ratio (r=-0.80, P<0.01). Lateral shortening was greater in the patients than in the controls (P<0.01). The asynchrony index was significantly greater in the patients than in the controls (P<0.01), and correlated with the right-to-left systolic pressure ratio (r=0.64, P=0.02) and the left ventricular end-diastolic pressure (r=0.79, P<0.01). The altered distribution of regional circumferential shortening results in an increased heterogeneity of regional systolic motion. These findings may have important implications for the assessment of ventricular function in patients with right ventricular pressure overload.

Adult↗

A streptavidin mutant with altered ligand-binding specificity.

The biotin-binding site of streptavidin was modified to alter its ligand-binding specificity. In natural streptavidin, the side chains of N23 and S27 make two of the three hydrogen bonds with the ureido oxygen of biotin. These two residues were mutated to severely weaken biotin binding while attempting to maintain the affinity for two biotin analogs, 2-iminobiotin and diaminobiotin. Redesigning of the biotin-binding site used the difference in local electrostatic charge distribution between biotin and these biotin analogs. Free energy calculations predicted that the introduction of a negative charge at the position of S27 plus the mutation N23A should disrupt two of the three hydrogen bonds between natural streptavidin and the ureido oxygen of biotin. In contrast, the imino hydrogen of 2-iminobiotin should form a hydrogen bond with the side chain of an acidic amino acid at position 27. This should reduce the biotin-binding affinity by approximately eight orders of magnitude, while leaving the affinities for these biotin analogs virtually unaffected. In good agreement with these predictions, a streptavidin mutant with the N23A and S27D substitutions binds 2-iminobiotin with an affinity (Ka) of 1 x 10(6) M-1, two orders of magnitude higher than that for biotin (1 x 10(4) M-1). In contrast, the binding affinity of this streptavidin mutant for diaminobiotin (2.7 x 10(4) M-1) was lower than predicted (2.9 x 10(5) M-1), suggesting the position of the diaminobiotin in the biotin-binding site was not accurately determined by modeling.

Binding Sites↗