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H Takagi

Publications and source records attributed to H Takagi.

At least 433 records · Page 24Linked to original sources
PubMed1996

LFA-1 (CD11a/CD18) and ICAM-1 (CD54) antibodies attenuate superoxide anion release from polymorphonuclear leukocytes in rats with experimental acute pancreatitis.

The inhibitive effects of anti-CD11a/CD18 (LFA-1) and anti-CD54 (ICAM-1) antibodies on the generation of superoxide anion (O2-) by polymorphonuclear leukocytes (PMNs) was elucidated in rats induced with experimental acute pancreatitis. We investigated the generation of O2- by PMNs in two protocols: in the first, we measured the active oxygen-producing ability of PMNs isolated from blood in normal rats; in the second, we measured it from blood, peritoneal cavity, and bronchial alveolar lavage fluid in rats 3 h after the induction of pancreatitis. In normal rats, although LFA-1 antibody attenuated the generation of O2-, ICAM-1 antibody did not. However, in pancreatitis rats, both LFA-1 and ICAM-1 antibodies reduced the generation of O2- by PMNs isolated from blood and the peritoneal cavity. These results showed not only that both LFA-1 and ICAM-1 antibodies have a protective effect on the generation of O2-, but also that LFA-1 has a direct inhibitive effect on the generation of O2- by PMNs in this model. Furthermore, histological studies showed there to be less neutrophil accumulation in the lungs of LFA-1- and ICAM-1-treated animals compared to control animals.

Acute Disease↗
PubMed1996

Clinical significance of carcinoma invasion of the extrapancreatic nerve plexus in pancreatic cancer.

To elucidate the clinical significance of neural invasion in pancreatic carcinoma, a clinicopathological study was performed. Neural invasion is a common feature of pancreatic carcinoma whose clinical significance has not yet been determined. Over a period of > 10 years, 129 of 204 (63%) patients with pancreatic carcinoma underwent resection by extensive radical surgery. A clinicopathological study of those specimens of pancreatic carcinoma was performed, with particular reference to neural invasion. Intrapancreatic neural invasion was observed in 116 of 129 (90%), of which 80 (69%) showed extrapancreatic nerve plexus involvement. A statistically significant (p < 0.001) correlation between the grade of intrapancreatic neural invasion and extrapancreatic nerve plexus invasion was observed. The postoperative survival rate for patients with extrapancreatic nerve plexus involvement was significantly (p < 0.001) lower than that for patients without extrapancreatic nerve plexus involvement. Patients who survived for > 3 years after operation had no extrapancreatic nerve plexus invasion even when portal vein wall invasion was observed.

Carcinoma↗
PubMed1996

Molecular genetics of hyperparathyroid disease.

Information on genetic abnormalities in primary hyperparathyroidism has accumulated gradually. Genetic alterations responsible for tumorigenesis have been identified in multiple endocrine neoplasia types 1 and 2. Point mutations in a calcium-sensing receptor gene were recently found to be responsible for familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidism. Evidence has been provided that abnormalities of cell cycle regulation participate at tumorigenesis in parathyroid adenoma and carcinoma. Clonal analysis has shown that in renal hyperparathyroidism the parathyroid glands initially grow diffusely and polyclonally, after which foci of nodular hyperplasia are transformed to monoclonal neoplasia. Somatic changes of specific genes have been suspected of being responsible for parathyroid tumorigenesis in renal hyperparathyroidism. However, the genetic loci responsible for the frequent monoclonality largely remain to be identified, and heterogeneous genetic abnormalities may contribute to the progression of secondary parathyroid hyperplasia.

Adenoma↗
PubMed1996

Proposal for two new genera, Brevibacillus gen. nov. and Aneurinibacillus gen. nov.

16S rRNA gene sequences of the type strains of 11 species belonging to the Bacillus brevis and Bacillus aneurinolyticus groups were determined. On the basis of the results of gene sequence analyses, these species were separated into two clusters. The B. brevis cluster included 10 species, namely, Bacillus brevis, Bacillus agri, Bacillus centrosporus, Bacillus choshinensis, Bacillus parabrevis, Bacillus reuszeri, Bacillus formosus, Bacillus borstelensis, Bacillus laterosporus, and Bacillus thermoruber. Bacillus aneurinolyticus and Bacillus migulanus belonged to the B. aneurinolyticus cluster. Moreover, the two clusters were phylogenetically distinct from other Bacillus, Amphibacillus, Sporolactobacillus, Paenibacillus, and Alicyclobacillus species. On the basis of our data, we propose reclassification of the B. brevis cluster as Brevibacillus gen. nov. and reclassification of the B. aneurinolyticus cluster as Aneurinibacillus gen. nov. By using 16S rRNA gene sequence alignments, two specific PCR amplification primers were designed for differentiating the two new genera from each other and from other aerobic, endospore-forming organisms.

Bacillus↗
PubMed1996

Detection of ras gene mutations in perioperative peripheral blood with pancreatic adenocarcinoma.

Surgeons wish to know of any correlation between an operation and the incidence of metastasis. In perioperative periods, pancreatic cancer cells were identified by detecting mutant K-ras gene by two-step PCR and RFLP analysis in blood samples taken from peripheral blood. In no case was K-ras point mutation detected in blood before operation, although the mutant hand was observed in all cases at the time the lesion was resected. Surprisingly, in five of ten cases, positive bands were identified just after laparotomy, before we had reached the primary lesion. In almost all cases, mutant K-ras was detected until the fourteenth postoperative day. These findings suggest that cancer cells exist in the circulation, and have a potential for hematogenous metastasis during the perioperative period. In conclusion, surgical stress causes hematogenous dissemination of pancreatic cancer cells, and surgeons should employ the appropriate anti-metastasis therapy in the perioperative period.

Adenocarcinoma↗
PubMed1996

Proliferating cell nuclear antigen expression in papillary thyroid carcinoma.

AIMS: To correlate the expression of proliferating cell nuclear antigen (PCNA) with various clinicopathological features of papillary thyroid carcinoma. METHODS: Sections from 131 formalin fixed, paraffin wax embedded papillary thyroid carcinomas were stained with a monoclonal antibody (PC10) directed against PCNA using the avidin-biotin immunoperoxidase (ABC) method. PCNA immunoreactivity was based on the PCNA labelling index (LI) following evaluation of at least 1000 tumour cells, and expressed as follows: grade A (LI < 10%), grade B (10% < or = LI < 25%), and grade C (LI > or = 25%). The relation between PCNA expression in these three groups and other clinicopathological factors, such as sex, age, tumour size, nodal metastases, and histological differentiation, were examined. RESULTS: Based on the labelling index, 57 (43.5%) cases were graded as A, 46 (35.1%) as B, and 28 (21.4%) as C. The female-:male ratios were 6.13:1 for group A, 2.83:1 for group B, and 2.11:1 for group C. The mean (SD) ages of the patients were 39.0 (16.1) in group A, 53.5 (14.4) in group B, and 55.8 (13.3) years in group C. The correlation between age and PCNA grade was strongest in women. CONCLUSIONS: PCNA immunoreactivity is correlated with sex and age in patients with papillary thyroid tumours.

Adolescent↗
PubMed1996

Inhibition of human complement-dependent cell lysis by bovine aortic endothelial cells transfected with membrane-bound complement-regulatory factor (DAF and HRF20) gene using a retroviral vector.

The endothelial cells (EC) of xenografts are the target of hyperacute rejection induced by complement activation via the classical and/or the alternative pathway. To protect these cells from the attack of human complement, decay-accelerating factor (DAF, CD55) and homologous restriction factor 20 (HRF20, CD59), which belong to human complement regulatory factors, were transfected into bovine aortic EC (BAEC) using retroviral vector. Cell surface expression of DAF and HRF20 on BAEC transfectants (BAEC/DAF, BAEC/HRF20) is comparable to that on human umbilical vein EC. Phosphatidyl inositol-phospholipase C treatment diminished or abolished cell surface expression of DAF and HRF20 on BAEC. The addition of human serum to BAEC led to complement-dependent cell lysis, whereas practically no lysis was observed after addition of human serum to BAEC/DAF and BAEC/HRF20. The addition of human serum plus rabbit complement to BAEC/DAF and BAEC/HRF20 caused complement-dependent cell lysis that was comparable to that observed for BAEC. These data demonstrate that xenograft EC transfected with DAF or HRF20 cDNA using retroviral vector are protected from complement-dependent cell lysis.

Animals↗
PubMed1996

Oxyphil cell function in secondary parathyroid hyperplasia.

Oxyphil cell function in secondary parathyroid hyperplasia due to chronic renal failure was evaluated using in situ hybridization and heterotransplantation of parathyroid tissue. In situ hybridization and histologic analysis were performed on continuous frozen sections using 22 parathyroid tissues. A restricted area composed exclusively of oxyphil cells was observed in 10 specimens, and an area of only chief cells was found in 12 specimens. Silver grains demonstrating the existence of parathyroid hormone (PTH) mRNA were 18.8 +/- 7.8 (mean +/- SD) in oxyphil cells while those in chief cells were 17.2 +/- 7.5. PTH mRNA was abundant in both the oxyphil and chief cells. Further analysis of oxyphil cell function was assessed by the heterotransplantation of parathyroid nodules, consisting exclusively of oxyphil or chief cells, into nude mice. The function of these implants was assessed by measuring the concentration of human intact PTH which did not cross-react with mouse PTH. Serum PTH concentrations were correlated with the volume of implanted tissue. Elevations of PTH concentrations were similar in the mice transplanted with oxyphil or chief cells, indicating that both cell types had similar PTH secretory activity. The basic histologic characteristics of both cell types were not altered following transplantation. These results demonstrate that oxyphil cells in secondary parathyroid hyperplasia synthesize and secrete PTH, and that this secretion contributes to the pathophysiology of hyperparathyroidism.

Alkaline Phosphatase↗
PubMed1996

Coupling of gonadotropin-releasing hormone receptor to Gi protein in human reproductive tract tumors.

The signaling pathway by which GnRH acts in peripheral tumors is distinct from that in the anterior pituitary. We attempted to identify the guanosine triphosphate (GTP)-binding protein (G protein) subtypes linked to GnRH receptor in the genital tract tumor membranes. Surgically removed ovarian carcinomas and uterine leiomyosarcomas were screened for GnRH receptor expression before plasma membrane isolation. The G alpha i was detected by immunoblotting of membrane extracts with specific antibody and pertussis toxincatalyzed ADP-ribosylation from nicotinamide adenine dinucleotide. Membrane phosphotyrosine phosphatase activity was determined as a GnRH-sensitive membrane event using synthetic substrate p-nitrophenyl in a spectrophotometric assay. Pertussis toxin, but not cholera toxin, brought about ADP-ribosylation of an immunodetected G alpha i of 41 kDa in the GnRH receptor-positive tumor membrane. Incubation with a GnRH analog and GTP decreased the ADP-ribosylation activity in a dose-dependent manner; a half-maximal effect occurred with 30 nmol/L buserelin (P < 0.01). The apparent inhibition by GnRH of the ADP-ribosylation demonstrated that GnRH resolved the alpha-subunit of the Gi to GTP-bound form in the membranes. The action of GnRH was neutralized by a competitive antagonist, antide. Pretreatment of the membrane with the pertussis toxin completely inhibited GnRH-sensitive phosphotyrosine phosphatase activity (P < 0.01). These data demonstrate the coupling of GnRH receptor to Gi protein subfamily. The Gi which couples GnRH receptor to the effector may define the difference of responses by peripheral tumor and the anterior pituitary.

Adenosine Diphosphate Ribose↗
PubMed1996

Reaction of adenine with 6-hydroxyestrogen 6-sulfates: model compounds to demonstrate carcinogenesis by estrogen.

To examine carcinogenesis by estrogens, we investigated the reactivity of 6-hydroxyestrogen 6-sulfates. Two epimeric 6-sulfates, pyridinium 3-methoxyestra-1,3,5(10)-trien-6 alpha-yl sulfate (1) and its 6 beta-isomer (2), were synthesized as model compounds and reacted with adenine under mild conditions to give two common products in the ratios of approximately 3:1 and 5:1, respectively. The major product was identified as N6-[3-methoxyestra-1,3,5(10)-trien-6 beta-yl] adenine (10), accompanied with its 6 alpha-isomer (9), by comparison with synthetic specimens. These results imply that, in the metabolism of naturally occurring estrogens, hydroxylation at the C6-position and subsequent sulfoconjugation of the benzylic hydroxyl group may produce sulfates which react with DNA to initiate carcinogenesis.

Adenine↗
PubMed1996

[Relation among lifestyle, social network, blood pressure and serum lipids in the elderly].

The relationships among seven lifestyle factors including stress, which is focused on as a risk factor for cardiovascular disease recently, social network, blood pressure and serum lipids in the elderly were examined in a cross sectional study of 85 males and 65 females aged 60 years or over in the city of Sayama, Saitama Prefecture. The seven lifestyle factors were as follows: (1) amount of alcohol consumption, (2) cigarette smoking, (3) Physical exercise, (4) sleeping time per night, (5) nutritional balance, (6) body weight, and (7) stress. As social network factors, marital status and coping factor for stress and/or anxiety were introduced. Stressful life events strongly associated with stress status were also discussed. In this study, it was clear that age, alcohol consumption, stress status and stressful life events caused higher blood pressure. On the other hand, the social network was associated with lifestyle status and a controlled blood pressure level. Obesity and physical exercise were significantly associated with serum lipids. There results suggest that it is very important for the maintenance and promotion of health and risk reduction of disease among the elderly to control socio-psychological factors such as stress and stressful life event, and that a social network helps maintain a healthy lifestyle.

Aged↗
PubMed1996

Incidentally discovered adrenocortical adenomas are not fully nonfunctioning: immunohistochemical and dispersed adrenocortical cell study.

To clarify the precise function of incidentally discovered adrenocortical adenoma, immunohistochemical and dispersed adrenal cell studies were performed. We have recently seen five patients with so-called nonfunctioning adrenocortical adenoma. Diurnal variation in plasma cortisol and suppression of plasma cortisol and urine 17-hydroxycorticosteroids in response to dexamethasone administration revealed adrenocortical function within normal limits in all cases, and no signs or symptoms of adrenal steroid hormone excess were evident. Since a high uptake of iodomethylnorcholesterol was recognized in each adrenal mass, it was supposed that these adrenal tumors produced steroid hormone to a certain extent, and each patient received unilateral adrenalectomy. P450c17, a key enzyme involved in cortisol production, was expressed in the tumor region in all cases in an immunohistochemical study. Upon in vitro steroidogenesis with dispersed adrenal cells in two cases, all steroid hormones measured except for aldosterone (progesterone, 17 alpha-hydroxyprogesterone, pregnenolone, 17 alpha-hydroxypregnenolone, 11-deoxycortisol, cortisol, 11-deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, dehydroepiandrosterone and androstenedione) were produced in a culture medium. The results indicated that these tumors possessed the capacity for cortisol production, which was in agreement with the results of an iodomethyl-norcholesterol scintigraphy. All patients with mild hypertension or diabetes mellitus had no signs or symptoms of steroid hormone excess, but they could potentially develop a steroid excess syndrome such as Cushing's syndrome in the future.

17-Hydroxycorticosteroids↗
PubMed1996

Identification and characterization of vascular endothelial growth factor receptor (Flt) in bovine retinal pericytes.

Vascular endothelial growth factor (VEGF) plays an important role in the hypoxia-stimulated neovascularization of ischemic retinal diseases such as proliferative diabetic retinopathy. VEGF exerts its effect through two known high-affinity tyrosine kinase receptors, named kinase insert domain-containing receptor (KDR) and the fms-like tyrosine kinase (Flt). VEGF receptors are located primarily on endothelial cells, although receptors on a few other nonocular cell types also have been described. In the present study, we demonstrate the expression of Flt, but not KDR, in bovine retinal pericytes (BRPCs). Although KDR is expressed predominantly in retinal endothelial cells, Northern blot analysis demonstrated substantial expression of the Flt gene in BRPCs without detection of KDR despite using polyadenylated RNA. Hypoxia increased Flt gene expression in BRPCs (2.7-fold, P < 0.01). 125I-labeled VEGF binding analysis on BRPCs demonstrated two apparent high-affinity receptor subtypes (Kd = 14 and 215 pmol/l), with 2.9 x 10(4) and 1.4 x 10(5) receptors/cell, respectively. 125I-VEGF affinity cross-linking demonstrated VEGF-specific binding complexes at 150, 172, 187, and 200 kDa under reducing conditions. Western blot analysis using an anti-phosphotyrosine antibody demonstrated VEGF-induced tyrosine phosphorylation of several proteins. VEGF stimulation had little effect on initial BRPCs growth rates but significantly increased BRPCs number after 7 days. These results suggest that two classes of high-affinity VEGF receptors are present on BRPCs, at least one of which is analogous to Flt and is capable of intracellular protein phosphorylation. Thus, VEGF might regulate the function of both retinal endothelial cells and retinal pericytes to induce pathological angiogenesis and vascular remodeling during proliferative diabetic retinopathy and other ischemic retinal diseases.

Animals↗
PubMed1996

Endothelin protein expression in tear glands of the rabbit.

PURPOSE: Endothelin-1 (ET-1) has been found to accelerate rabbit corneal epithelial wound healing in vivo and proliferation of rabbit and bovine epithelial cells in vitro. We have now determined that endothelin-like immunoreactivity (ET-LI) is present in the tear fluid of New Zealand white rabbits, and we have addressed the question of whether it is produced by the tear glands (lacrimal gland and Harderian gland). METHODS: Tears were obtained with capillary pipettes and lacrimal gland fluid was collected by cannulation. ET-LI was determined with a sandwich-enzyme immunoassay. The reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to determine if there are gene transcripts for prepro ET-1 in tear glands. ET-LI in the tear glands was evaluated using immunohistochemistry. RESULTS: The tears contained 13.85 +/- 3.94 pg/ml (mean +/- SEM, n = 6) ET-LI and the lacrimal gland fluid had 24.90 +/- 6.00 pg/ml (n = 6). The plasma contained 0.89 +/- 0.20 pg/ml (n = 6). Gene transcripts were identified for prepro ET-1 in the lacrimal and Harderian glands. Specific staining for ET-LI was found in the epithelial cells of the ducts of the lacrimal gland and the acinar cells of the Harderian gland. CONCLUSIONS: The higher concentrations of ET-LI in the tears and the lacrimal gland fluid than in plasma along with prepro ET-1 gene transcripts in the tear glands suggest that they secrete ET-1.

Animals↗