Search PubMed⌕ Search

Biomedical subjects

T Ohta

Publications and source records attributed to T Ohta.

At least 631 records · Page 35Linked to original sources
PubMed1995

Alendronate distributed on bone surfaces inhibits osteoclastic bone resorption in vitro and in experimental hypercalcemia models.

Alendronate is an aminobisphosphonate that acts as a potent inhibitor of osteoclastic bone resorption. To understand the mechanism of action of alendronate in vivo, in this study we investigated the relationship between distribution of [14C]-alendronate in rat bone and its effects on bone resorption in vitro or in rat hypercalcemic models. A single IV dose of 0.05 approximately 1.25 mg/kg inhibited the increase in plasma calcium level induced by bovine PTH or 1 alpha(OH)D3. The minimal effective dose of pamidronate (1.25 mg/kg) and etidronate (over 31.25 mg/kg) were at least 5 times and 25 times, respectively, higher than the dose of alendronate in the rat hypercalcemic model prepared by 1 alpha(OH)D3. The relative potencies of compounds in the hypercalcemic rat models reflected those of inhibitory effects on bone resorption in vitro. We conducted the ivory-slice assay under two conditions: (a) addition of a given bisphosphonate after adherence of the osteoclasts; and (b) preincubation of the ivory slices with a given bisphosphonate. The inhibitory IC50 values of alendronate under condition (b) were similar to those under condition (a). To evaluate the interaction between osteoclasts and alendronate in bone, we investigated the localization of [14C]-alendronate in the tibia of growing rats (4-day-old rats). Alendronate did not distribute uniformly in the tibia. At 1 day after injection (0.05 mg SC), dense labeling was seen primarily under osteoclasts. We injected 0.05 mg/kg of [14C]-alendronate (single i.v.) into rats [14C]-alendronate was rapidly eliminated from plasma, and mainly distributed to the bone in rats. These data suggest that alendronate which distributed on bone surface mainly contributed to the antihypercalcemic action in vivo.

Alendronate↗
PubMed1995

Surgical strategy for carcinoma of the pancreas head area based on clinicopathologic analysis of nodal involvement and plexus invasion.

BACKGROUND: The pattern of tumor spread, vis-à-vis nodal involvement and invasion of the extrapancreatic plexus (Plx), has not been thoroughly described for carcinoma of the pancreatic head area. METHODS: From 1973 to 1991, 110 patients (49 with carcinoma of the pancreatic head [Ph], 29 with distal bile duct cancer [Bi], and 32 with carcinoma of the papilla of Vater [Pv]) underwent pancreatectomy at Kanazawa University Hospital. Nodal involvement and Plx invasion were precisely evaluated by histopathologic examination. RESULTS: Thirty-seven (76%) of the 49 patients with Ph, 20 (69%) of the 29 with Bi, and 14 (44%) of the 32 with Pv had nodal involvement. The lymph nodes most commonly involved for Ph were the posterior pancreaticoduodenal lymph nodes (numbers 13a [superior] and 13b [inferior]), the superior mesenteric lymph nodes (number 14), the paraaortic lymph nodes (number 16), and the anterior pancreaticoduodenal lymph nodes (number 17) (13a, 51%; 13b, 47%; 14, 36.7%; 16, 18.4%; 17a, 33%; 17b, 22%). In patients with Bi, lymph nodes around the hepatoduodenal ligament (number 12) and lymph nodes numbers 13a and 14 were most commonly involved (12, 27.6%; 13a, 51.7%; 14, 34.5%). In patients with Pv, lymph node numbers 13b and 14 were most frequently involved (13b, 34.4%; 14, 15.6%). No significant correlation was noted between the tumor size and nodal involvement in these three lesions. Nodal involvement was an important prognostic factor for carcinoma of the pancreatic head area. Plx invasion in these three carcinomas was observed in 61% of patients with Ph, 29% of patients with Bi, and 3% of patients with Pv. CONCLUSIONS: Nodal involvement and Plx invasion differed significantly among carcinomas of the pancreatic head area. We believe that nodal dissection of at least group number 14 is needed for Ph, Bi, and Pv cancers. In addition, dissection of lymph nodes of number 16 and the Plx around the superior mesenteric artery and celiac axis are needed in Ph cancer. Plx dissection of the first portion of plexus pancreaticus capitalis is needed in Bi cancer.

Actuarial Analysis↗
PubMed1995

Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas.

We examined the expression of basic fibroblast growth factor (FGF) and FGF receptor by immunohistochemistry in 32 human pancreatic ductal adenocarcinomas. Mild to marked basic FGF immunoreactivity was noted in 19 (59.4%) of the 32 tumours examined, and 30 (93.3%) of the tumours exhibited a cytoplasmic staining pattern against FGF receptor. The tumours were divided into two groups according to the proportion of positively stained tumour cells: a low expression group (positive cells < 25%) and a high expression group (positive cells > or = 25%). No statistically significant difference in tumour size, differentiation, metastases or stage was found between the low and high basic FGF expression groups. However, a significant correlation was found between FGF receptor expression level and the presence of retroperitoneal invasion, lymph node metastasis, and tumour stage. In addition, low FGF receptor expression was significantly associated with a longer post-operative survival as compared with high FGF receptor expression, whereas there was no significant difference in post-operative survival between the low and high basic FGF expression groups. Increased expression of FGF receptor is correlated with the extent of malignancy and post-operative survival in human pancreatic ductal adenocarcinomas. Thus, overexpression of FGF receptor may prove to be a more useful prognostic marker than basic FGF expression level in pancreatic cancer patients.

Adult↗
PubMed1995

Establishment of new interferon-gamma-resistant mutant cells with dominant phenotypes.

We established interferon-gamma-resistant (IGR) cells from a human colon adenocarcinoma cell line, LoVo. Their resistance was extremely high, and the ED50 values of IFN-gamma were > 10(5) IU/ml. Interestingly, although IGR-5 cells were still sensitive to the antiproliferative effect of IFN-alpha, the cells lost responsiveness to the antiviral effects of both IFN-alpha and gamma. Another clone, IGR-53, was unresponsive to both the antiproliferative and antiviral effects of either IFN-alpha or gamma. Furthermore, the IFN-gamma-resistant phenotypes of IGR cells were apparently dominant to the parental LoVo cells based on complementation tests. Although IGR-53 cells lack IFN-gamma receptors, IGR-5 cells seemed to have functional IFN-gamma receptors and processing mechanisms of IFN-gamma bound to the receptors. Northern analysis showed that IGR-5 cells responded to IFN-gamma and alpha, but the enhancement of IRF-1 expression by IFN-gamma was markedly suppressed.

Adenocarcinoma↗
PubMed1995

Isolation and characterization of a novel gene deleted in DiGeorge syndrome.

The region commonly deleted in DiGeorge syndrome (DGS) has been localized at 22q11.1-q11.2 with the aid of a high resolution banding technique. A 22q11 specific plasmid library was constructed with a microdissection and microcloning method. Dosage analysis proved three of 144 randomly selected microclones to detect hemizygosity in two patients with DGS. Two of the clones were found to contain independent low-copy-number repetitive sequences, all of which were included in the region deleted in the DGS patients. Screening of the cosmid library and subsequent cosmid walking allowed us to obtain two cosmid contigs corresponding to the microclones within the deletion (contig 1 and contig 2), whose order fluorescence in situ hybridization identified as centromere-contig 1-contig 2-telomere on 22q. By direct selection strategy using one of the cosmids of contig 1, a 4.3 kb cDNA was obtained from fetal brain cDNA library. Sequence analysis of the cDNA revealed an open reading frame encoding 552 amino acids which had several characteristics of DNA-binding proteins. The gene, designated LZTR-1, which was transcribed in several essential fetal organs, proved to be hemizygously deleted in seven of eight DGS patients or its variants, but not in one DGS patient and GM00980. Although LZTR-1 does not locate in the shortest region of overlap, several of its structural characteristics identifying it as transcriptional regulator suggest that it plays a crucial role in embryogenesis and that haploinsufficiency of this gene may be partly related to the development of DGS.

Amino Acid Sequence↗
PubMed1995

Structural composition of hammerhead ribozymes.

Eleven kinds of hammerhead ribozymes were designed and synthesized to investigate the structural composition of the complexes and to find suitable crystallization conditions, the substrate chains having been modified to prevent hydrolysis. Electrophoresis patterns indicated that the two strands except for the substrate chain form a binary complex and that they form a ternary complex when mixed with the substrate chain. Both complexes were crystallized. The crystal of the binary complex belongs to a Laue symmetry of 32 (space group of P321, P3(1)21, or P3(2)21) with cell dimensions of a = b = 53.4 and c = 59.4 A. The volume per one nucleotide allows the asymmetric unit to contain one binary complex. Our results suggest that the catalytic part forms a rigid ribozyme structure which induces a scissile reaction when the substrate is bound, in a similar manner to an enzyme protein.

Base Sequence↗
PubMed1995

Metastasis-promoting activity of a novel molecule, Ag 243-5, derived from mycoplasma, and the complete nucleotide sequence.

We found that mycoplasma-infected cells have a higher ability to metastasize in vivo than non-mycoplasma-infected cells. To investigate this phenomenon, we obtained a monoclonal antibody, MAb 243-5, by immunization with Mycoplasma arginini-infected RPMI 4788 cells. This MAb recognized a mycoplasmal protein with an MW of 47 kDa and completely inhibited the experimental metastasis of M. arginini-infected RPMI 4788 cells using a nude mouse model. Using this MAb, we purified a molecule called Ag 243-5 and determined the N-terminal amino acid sequence and clarified the entire nucleotide sequence of the Ag 243-5 gene. PCR analysis showed the existence of a homologous gene in Mycoplasma hyorhinis. Four sequential injections of Ag 243-5 (30 micrograms/shot) promoted the experimental metastasis of non-mycoplasma-infected RPMI 4788 cells more than 10-fold using a nude mouse model. Ag 243-5 also promoted the experimental metastasis of the non-mycoplasma-infected mouse colon cancer cell line colon 26. This metastasis-promoting effect was neutralized by MAb 243-5.

Amino Acid Sequence↗
PubMed1995

Ca2+ entry activated by emptying of intracellular Ca2+ stores in ileal smooth muscle of the rat.

1. The effects of depletion of intracellular Ca2+ stores on muscle tension and the intracellular Ca2+ concentration ([Ca2+])i were studied in fura-2 loaded longitudinal smooth muscle cells of the rat ileum. 2. After exposure to a Ca(2+)-free solution, application of Ca2+ caused a small contraction and a rise in [Ca2+]i, both of which were potentiated when the muscle was challenged with carbachol or caffeine before the addition of Ca2+. 3. Cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase, dose-dependently decreased tension development and the rises in [Ca2+]i induced by carbachol and caffeine in the Ca(2+)-free solution, but conversely increased the Ca(2+)-induced responses even in the presence of the voltage-dependent Ca2+ channel blockers, methoxyverapamil and nifedipine. 4. The contraction and rise in [Ca2+]i evoked by Ca2+ gradually declined with time after removal of CPA, while the reverse was the case for the responses to carbachol and caffeine. 5. The Ca(2+)-induced contraction and rise in [Ca2+]i in the presence of CPA were inhibited by the replacement of Na+ with K+ or Cs+, and by the addition of Cd2+, Ba2+, Ni2+ or La3+. 6. The influx of Mn2+ was much greater in extent in the presence of CPA than in its absence. 7. These results suggest that the emptying of intracellular Ca2+ stores may activate Ca2+ influx not associated with voltage-dependent Ca2+ channels in the rat ileal smooth muscle.

Animals↗
PubMed1995

A new case of apoA-I deficiency showing codon 8 nonsense mutation of the apoA-I gene without evidence of coronary heart disease.

We report a 39-year-old Japanese man with HDL and apoA-I deficiency as well as data from members of his family. Corneal opacity and a stomatocyte were found but not tonsillar hypertrophy, xanthomas, or splenomegaly. His serum HDL cholesterol, apoA-I, apoA-II, and LDL cholesterol levels were t mg/dL, < 3 mg/dL, 6 mg/dL, and 175 mg/dL, respectively. Plasma triglyceride, phospholipid, apoB, apoC-III, and apoE levels were all within normal limits. Lecithin:cholesterol acyltransferase activity was half of normal, while lipoprotein lipase and hepatic triglyceride lipase activities were within normal limits. ApoA-I deficiency was confirmed by combined isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by an immunoblotting method. We surveyed the apoA-I gene of the patient and five of his family members by direct sequencing after amplification by polymerase chain reaction and found a codon 8 nonsense mutation (TGG --> TAG, Trp --> stop) in exon 3 of the apoA-I gene. The results of a pedigree analysis by DNA sequencing and restricted fragment length polymorphism (Sty I) were consistent with an autosomal codominant trait. Coronary angiography was performed to evaluate coronary atherosclerosis, but no significant luminal narrowing was detected. An intracoronary ultrasound study showed mild intimal hyperplasia in segment 6. In summary, this is a case of apoA-I deficiency without evidence of coronary heart disease.

Adolescent↗
PubMed1995

Different effects of subclasses of HDL containing apoA-I but not apoA-II (LpA-I) on cholesterol esterification in plasma and net cholesterol efflux from foam cells.

We investigated the effects of subclasses of plasma LpA-I (HDL containing apoA-I but not apoA-II) on cholesterol esterification in plasma and net cholesterol efflux from foam cells. LpA-I was composed of particles of three diameters: large (11.1 nm; Lg-LpA-I), medium (8.8 nm; Md-LpA-I), and small (7.7 nm; Sm-LpA-I). Plasma concentrations of LpA-I were positively correlated only with the level of Lg-LpA-I. Plasma concentrations of Lg-LpA-I were inversely correlated with the rate of cholesterol esterification in plasma and VLDL- and LDL-depleted plasma. Plasma concentrations of Md-LpA-I and Sm-LpA-I did not correlate with the rate of cholesterol esterification in plasma or VLDL- and LDL-depleted plasma. When macrophage foam cells were incubated with Md- and Sm-LpA-I, cellular cholesterol mass was reduced by approximately 70%. In contrast, the cellular cholesterol-reducing capacity of Lg-LpA-I was negligible. Lg-LpA-I inhibited net cholesterol removal from foam cells that was mediated by Md- and Sm-LpA-I and cholesteryl ester production with these particles. These results suggest that Md- and Sm-LpA-I may actively participate in cellular cholesterol removal and cholesterol esterification in plasma and HDL, while Lg-LpA-I may regulate these functions of Md- and Sm-LpA-I.

Adolescent↗
PubMed1995

Diffuse leptomeningeal enhancement, "ivy sign," in magnetic resonance images of moyamoya disease in childhood: case report.

We report three cases of children with moyamoya disease who revealed prominent leptomeningeal enhancement on postcontrast magnetic resonance (MR) images. Two of the children underwent bilateral extracranial-intracranial bypass operations because of ischemic symptoms. During the operations, a profuse pial arterial network was observed, which was considered to be the origin of the enhancement. The ischemic episodes disappeared after the operations, and the follow-up MR images showed marked reduction of the leptomeningeal enhancement. One of the three patients had an extracranial-intracranial bypass operation on one side, but postoperative MR images have not yet been obtained. We named this finding on postcontrast MR images "ivy sign," because it resembles ivy creeping on stones. Ivy sign seems to be a unique, characteristic feature of the pial network observed in moyamoya disease.

Brain Ischemia↗
PubMed1995

Sperm morphology and IMP distribution in membranes of spermatozoa of cyprinid fishes II.

The morphology and intramembranous particle (IMP) distribution of spermatozoa were investigated in four species of cyprinid fishes, Gnathopogon elongatus elongatus, Pseudogobio esocinus, Acheilognathus lanceolatus and Puntius tetrazona. In particular, observation of IMP distribution was conducted as an aspect of comparative spermatology in cyprinid fishes and was continued from a previous paper (Ohta et al., 1994 (8)). Although the fundamental structures of the spermatozoa were similar among the four species, the distribution of IMPs varied. Hexagonal (or parallelogrammic) arrays of IMPs on the sperm head membranes were present in G. elongatus elongatus, A. lanceolatus and P. tetrazona, but not in P. esocinus. The hexagonal arrays have now been confirmed to be present in twelve of the thirteen species of cyprinid fishes examined so far.

Animals↗
PubMed1995

Structure and activity of HYI killer toxin from Hansenula saturnus.

The primary structure of HYI killer toxin produced by Hansenula saturnus was determined in its reduced and pyridylethylated form, as well as the peptides resulting from protease digestion. It was found that the HYI killer toxin consisted of 87 amino acid residues and the molecular weight was calculated to be 9543 Da. It showed 87% homology with HM-1 killer toxin produced by H. mrakii, while there were multiple mutations including one amino acid deletion which, nevertheless, did not alter the strong cytocidal effect on sensitive yeasts.

Amino Acid Sequence↗
PubMed1995

Long-term follow-up of the reproducibility of carotid sinus hypersensitivity in patients with carotid sinus syndrome.

The reproducibility of carotid sinus hypersensitivity to carotid sinus massage was studied in the long-term follow-up of 8 patients with carotid sinus syndrome. A cardioinhibitory response was induced in 7 patients, while a vasodepressor response was found in the remaining patient. The 7 patients were treated with dual-chamber pacemaker implantation and the remaining patient was treated with propranolol. All of the patients remained asymptomatic during a follow-up period of 48 +/- 11 months. Carotid sinus massage during the follow-up period in patients with a cardioinhibitory response revealed asystolic intervals of 3 s or longer in 4 patients and in 3 patients at the second and third follow-up examinations, respectively, although there were no significant differences in the ventricular asystolic intervals between before, and 34 +/- 11 months and 48 +/- 11 months after treatment. However, each patient showed a wide variation in asystolic intervals. The differences in asystolic intervals between prior to treatment (first) and the third test were significantly greater than those between the first and the second test (2.4 +/- 1.2 s vs 0.7 +/- 0.6 s; p < 0.05). The one patient with a vasodepressor response had a decreased systolic blood pressure greater than 50 mmHg by carotid sinus massage at all three occasions. In conclusion, most patients with carotid sinus syndrome showed abnormal and variable responses to carotid sinus massage during long-term follow-up period although there was no recurrence of symptoms after treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Expression of aqualysin I (a thermophilic protease) in soluble form in Escherichia coli under a bacteriophage T7 promoter.

The thermophilic protease aqualysin I (AQI) gene (aquI), derived from Thermus aquaticus YT-1, was inserted under the control of the bacteriophage T7 promoter in an expression plasmid. The plasmid was introduced into two strains of E. coli JM109 (DE3), one carrying and one lacking an F' episome, which carries the lacIq gene. Upon cultivation the strain carrying an F' episome produced AQI as an insoluble fusion protein (74kDa) with the T7 gene 10 protein. This insoluble protein could not be processed into mature AQI by heat treatment and thus it had no proteolytic activity. On the other hand, when the strain lacking an F' episome was used as a host cell for aquI expression, non-induced, or leaky, expression occurred, and AQI was produced in a soluble form. This soluble protein could be processed into active AQI by heat treatment. Moreover, when a low concentration of IPTG (0.0125 mM) was added, the amount of active AQI was 2.7 times greater than that produced in a batch culture without induction.

Bacteriophage T7↗