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Biomedical subjects

T Taniguchi

Publications and source records attributed to T Taniguchi.

At least 415 records · Page 23Linked to original sources

Differential involvement of phospholipase C isozymes in Alzheimer's disease.

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. We demonstrated that an antibody to an isozyme of PLC, PLC-delta 1, produced intense staining of neurofibrillary tangles (NFT) in the brains of patients with Alzheimer's disease (AD). Western blot analysis using a specific antibody for PLC-delta 1 showed that the concentration of PLC-delta 1 protein was significantly higher in the cytosolic fraction of AD cortical tissues than in controls. The activity of PLC-delta 1, which hydrolyzes phosphatidylinositol, was not significantly different in the Alzheimer and control cytosolic fraction, indicating that the specific activity of PLC-delta 1 is decreased in Alzheimer brains. Western blot analysis also showed that the concentration of PLC-delta 1 and PLC-gamma 1 was significantly lower in the membraneous fraction of AD cortical tissues than in controls. These results suggest a differential involvement of PLC isozymes in AD.

Aged↗

Intraocular pressure response to intravitreal injection of endothelin-1 and the mediatory role of ETA receptor, ETB receptor, and cyclooxygenase products in rabbits.

Endothelin-1 (ET-1) affects intraocular pressure (IOP) in rabbits. First, we studied IOP responses to the intravitreal injection of various doses of ET-1 ranging from 5 ng to 5 micrograms in unanesthetized rabbits, and observed a transient rise in IOP, from 0.5 to 2 h in duration, invariably followed by a prolonged IOP reduction, lasting for more than 72 h in rabbits treated with 0.5 microgram and 5 micrograms of ET-1. ET-1 (0.05 microgram and 0.15 microgram) resulted in a prolonged IOP reduction without an early IOP rise. Both IOP rise and reduction were significantly related to the dose of ET-1. A masked, randomized, study revealed that the intraperitoneal administration of indomethacin (50 mg/kg) prior to ET-1 injection significantly reduced the ocular hypertensive response, but not th ocular hypotensive response, to ET-1. The ETA receptor selective antagonist, 97-139 (155 micrograms) had no effect on IOP when used alone. However, when used in combination with 0.5 microgram of ET-1, 97-139 significantly inhibited both the IOP rise (0.5-2 h) and reduction (8-96 h) caused by ET-1. The ETB receptor selective agonist, sarafotoxin S6c (0.5 microgram), caused a sustained IOP reduction of 2 to 96 h in duration without the initial IOP rise. We also determined the concentration of prostaglandin (PG) E2 in the aqueous humor using radioimmunoassay techniques on samples obtained at 1 and 24 h after ET-1 injection, and examined the effects of pretreatment with indomethacin or 97-139 on PGE2 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clinical significance of serial measurement of the serum levels of soluble interleukin-2 receptor and soluble CD8 in malignant lymphoma.

We serially measured the serum levels of soluble interleukin-2 receptor (sIL-2R) and soluble CD8 (sCD8) in 36 patients with malignant lymphoma (33 non-Hodgkin's lymphoma cases and three Hodgkin's disease cases). The level of serum sIL-2R was significantly elevated in patients with active disease (18) compared to those in remission (18), and correlated with the clinical stage of the lymphoma. The temporal profile of the sIL-2R level reliably represented the disease status, which was judged clinically, during the course of the disease. In three patients, the tumor bulk paralleled the sIL-2R level. On the other hand, a less significant correlation was found between the serum sCD8 level and disease activity. The serial measurement of sCD8 appeared to be less useful for monitoring the disease activity, although there was a significant correlation between the sCD8 and sIL-2R levels. This study indicates that serial measurement of the serum sIL-2R level may be useful for monitoring the tumor burden in response to treatment and for early detection of disease progression in malignant lymphoma.

Adult↗

[Restenosis after percutaneous transluminal coronary angioplasty in the elderly--risk factor analysis].

Utilization of percutaneous transluminal coronary angioplasty (PTCA) has dramatically expanded even in the management of elderly patients with coronary artery disease. However, restenosis after successful PTCA remains the major problem limiting the long-term efficacy of the procedure. Reported restenosis rates vary from 25 to 43%. In order to determine the relationship of restenosis to coronary risk factors in the elderly, we analyzed the data in 87 patients who had undergone PTCA and angiography before and 3 to 6 months after PTCA. Of these, 29 patients were 65 years of age or older (elderly group) and 58 were less than 65 years of age (younger group). Restenosis, defined as a luminal narrowing of greater than 50% at follow-up time, was found in 20 of the elderly group (69.0%), and in 26 (44.8%) of younger group (p < 0.0001). Total cholesterol, LDL cholesterol, apolipoprotein B (apo B), and the ratio of apoB/apoA1 in the elderly group were significantly lower than those in the younger group. HDL cholesterol levels were lower than 40 mg/dl in both groups (not significant). Each group was subdivided into two types; restenosis type and non-restenosis type. There were no significant differences in serum lipid, apolipoprotein, and lipoprotein(a) levels between the 2 subtypes in each group. The degree of coronary atherosclerosis calculated by Gensini's method, the number of damaged coronary vessels, diabetes mellitus, hypertension, and smoking did not appear to affect the rate of restenosis in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

[Vesico-uterine fistula after delivery: a case report].

A case of vesico-uterine fistula which occurred after natural childbirth is reported. A 33-year-old woman was admitted in February, 1993, complaining of urinary leakage from vagina immediately after natural childbirth. Excretory urogram showed an oval shaped extravasation outside the bladder, suggesting that the contrast medium went into the luminal space of the uterus. Subsequent cystoscopy showed a fistula on the posterior wall, probably the orifice of the fistula to the space. As these findings strongly suggested the vesico-uterine fistula, surgical operation was done. Rupture of the uterus was observed. Then hysterectomy was done because the rupture could not be repaired. Vesico-uterine fistula was thought to be the result of the rupture of uterus. Bladder side fistula was successfully repaired. Sixty eight cases of vesico-uterine fistula, including this case, in the Japanese literature have been reviewed and discussed the etiology, symptom and treatment.

Adult↗

The ocular hypotensive effect of the ETB receptor selective agonist, sarafotoxin S6c, in rabbits.

PURPOSE: Endothelin-1 (ET-1) is known to affect intraocular pressure (IOP) in rabbits, and the IOP response is likely to be mediated by the receptors ETA, ETB, or both. Sarafotoxin S6c (STX-S6c) is a selective agonist to ETB receptors. The authors attempted to clarify the role of ETB receptors in changes in IOP induced by ET-1 in rabbits using STX-S6c and to determine the relationship between the IOP response and various doses of STX-S6c. METHODS: Each concentration (10(-4) to 10(-7) M) of STX-S6c was injected intravitreally (20 microliters/eye) into one eye. The contralateral eye of each was used as a control. The IOP was measured periodically using a calibrated pneumatonometer. Indomethacin (50 mg kg-1) or vehicle (10 ml kg-1; 0.05 M phosphate buffer) was administered intraperitoneally twice, before and after intravitreal injection of STX-S6c (10(-5) M), and IOP was measured in the same protocol for 24 hours. RESULTS: In the STX-S6c (10(-4) and 10(-5) M) group, the IOP reduction was significant compared with the baseline (P < 0.05 to P < 0.01), starting from 6 and 4 hours and continuing until 192 and 72 hours after injection, respectively. A solution of 10(-6) M STX-S6c also resulted in significant reduction of IOP observed from 24 to 72 hours after injection (P < 0.05). The 10(-7) M solution of STX-S6c failed to affect IOP. The area under the curve of IOP response exhibited a significant correlation with the doses of STX-S6c (r = -0.856; P = 0.0001) in the treated eyes. Treatment with indomethacin failed to affect the IOP reduction caused by STX-S6c (10(-5) M). Ciliary injection and some dilatation of the iridial vessels were observed in eyes that received higher doses of STX-S6c. CONCLUSION: STX-S6c reduces the IOP in rabbits in a dose-dependent fashion, presumably mediated through the ETB receptors.

Amino Acid Sequence↗

[The effect of an endothelin receptor antagonist, 97-139, on intraocular pressure in rabbits].

We studied intraocular pressure (IOP) response to an intravitreal injection of 10(-5)M (20 microliters) endothelin-1 (ET-1) in unanesthetized rabbits, and found a transient IOP rise followed by a prolonged IOP reduction. ET-1 (10(-6)M) caused a sustained IOP reduction without an initial IOP rise. The ETA receptor selective antagonist, 97-139 (10(-2)M, 20 microliters), had no effect when used alone; however, when used in combination with ET-1 (10(-5)M), 97-139 (10(-2)M) significantly blocked the ocular hypotensive response to ET-1. 97-139 (10(-3)M), when used with 10(-6)M ET-1, also suppressed the IOP reduction induced by ET-1. Aqueous prostaglandin (PG) E2, determined by radioimmunoassay, was significantly elevated following intravitreal injection of ET-1 (10(-5)M). Prior injection of 97-139 (10(-2)M) significantly suppressed the elevation of aqueous PGE2 concentration caused by ET-1 (10(-5)M). These results suggest that both the IOP response and the elevation of aqueous PGE2 following ET-1 injection are at least partially mediated by ETA receptor.

Animals↗

[The effect of combination treatment consisted of 5'-deoxy-5-fluorouridine and medroxyprogesterone acetate for recurrent breast cancer patient].

The effect of the combination treatment consisted of 5'-deoxy-5-fluorouridine (5'-DFUR) and medroxyprogesterone acetate (MPA) was investigated in 20 recurrent breast cancer patients. Out of 20 patients, 8(40.0%) responded to the treatment. The average duration of response was 10.3 months. Response rates stratified by recurrence site were soft tissues 36.4%, bone 44.4%, liver 60.0% and lung 20.0%, respectively. No serious side effect except body weight gain, which was caused by MPA, was seen. In a 76-year-old woman with liver metastases, a marked response was obtained and has continued for more than 24 months. It was suggested that the combination of 5'-DFUR and MPA may be effective for recurrent breast cancer patients.

Administration, Oral↗

[Changes in plasma cytokine levels during lung surgery].

We studied the changes in plasma cytokine (IL-6 and IL-8) levels during lung surgery in 20 patients. The correlation between the changes in cytokine levels and surgical stress as well as the postoperative complications were examined. The levels of IL-6 and IL-8 increased shortly after the surgical incision and were 326 pg.ml-1 and 61 pg.ml-1 respectively, at the end of surgery. The changes in cytokine levels correlated well with the duration of surgery, blood loss and CPR levels for 2 days after the surgery. However, there were no severe postoperative complications in the present study. We conclude that the cytokines increase shortly after the surgical incision and the changes in cytokine levels correlate well with the surgical stress.

Acute-Phase Reaction↗

The effects of endothelin-1 on intraocular pressure and pupillary diameter in rabbits.

Endothelin-1 (ET-1) reduced intraocular pressure (IOP) in animals when administered topically. The time-course of IOP changes induced by ET-1, however, has not been fully documented. We studied the IOP response to different doses of intravitreally injected ET-1 ranging from 10(-7) to 10(-4) M in rabbits. In each animal one eye received 20 muL of ET-1 solution and the contralateral eye received the same amount of vehicle in a randomized, masked fashion. IOP was measured by a pneumatonometer prior to and periodically for at least 72 hours after the intravitreal injection. ET-1 in 10(-4) and 10(-5) M concentration elicited an IOP response consisting of an initial rise of 1- to 2-hour duration, and a subsequent prolonged reduction lasting for more than 72 hours. The use of 3 x 10(-6) and 10(-6) M solutions resulted in a prolonged IOP reduction without an early IOP rise. No significant IOP change was induced by 10(-7) M solution or the vehicle. No change was observed in pupillary diameters after injection of ET-1 in any dose. The aqueous prostaglandin E2 concentration was significantly increased at both 1 and 24 hours after 10(-5) M ET-1 injection.

Animals↗

IRF-1 and IRF-2 as regulators of the interferon system and cell growth.

Interferons (IFNs) are families of cytokines which have been discovered and extensively characterized in the context of host defense against viral infections. We have discovered two structurally related transcription factors, Interferon regulatory factor-1 (IRF-1) and IRF-2. These two factors, however, function not only as regulators of the IFN system, but are also key transcription factors in the regulation of cell cycle and apoptosis. These studies uncover a complex gene transcription network, by which the fate of cellular responses are determined depending on how the IRF transcription factors function in conjunction with other factors, and on the promoters of distinct genes under different conditions of the cells.

Animals↗

The effects of ETB receptor-selective agonist on IOP and blood-aqueous barrier in rabbit eyes: role of cyclooxygenase products.

The authors have reported that ET-1 and ETB receptor agonist, sarafotoxin S6c (STX-S6c), caused prolonged intraocular pressure (IOP) reduction in rabbit eyes in a dose-dependent fashion when injected intravitreally. The purpose of this study was to determine the effects of STX-S6c on the blood-aqueous barrier and also the possible role of cyclooxygenase products in modulating IOP. Indomethacin, a cyclooxygenase inhibitor (50 mg/kg), or its placebo was administered intraperitoneally 1 hour before or 1 hour before and 4 hours after the intravitreal injection of 0.5 micrograms of STX-S6c into one eye in a group of albino rabbits. The fellow eye received the vehicle only. IOP was measured prior to and periodically up to 120 hours after the injection using a calibrated pneumatonometer. One hour and 24 hours following the injection of STX-S6c (0.5 micrograms) with or without indomethacin, approximately 100 microL of aqueous humor was withdrawn by paracentesis. Protein concentration was measured by Lowry's method and PGE2 concentration was determined by radioimmunoassay. Both single and double dosings of indomethacin failed to prevent the IOP reduction caused by STX-S6c. The eyes injected with STX-S6c exhibited a significant elevation of both PGE2 and protein concentration at both 1 and 24 hours after injection. Pretreatment with indomethacin could significantly suppress the PGE2 and protein content of aqueous humor at both 1 and 24 hours after injection. ETB receptor agonist, STX-S6c, appears to induce the IOP reduction without affecting the cyclooxygenase pathway or disrupting the blood-aqueous barrier.

Animals↗

Serum concentrations of hepatocyte growth factor in breast cancer patients.

Hepatocyte growth factor (HGF) was first identified as a potent stimulator of hepatocyte growth and DNA synthesis. Later, it was shown that HGF can promote cell motility and cell proliferation in various types of cells, including tumor cells and endothelial cells. We have examined serum concentrations of HGF in breast cancer patients using an ELISA. Of 134 primary breast cancer patients, 49 (36.6%) showed a significant increase in the circulating level of HGF as compared to healthy controls. The increase in the HGF level was significantly associated with axillary lymph node metastases and histological evidence of venous invasion. No significant correlation between serum HGF concentrations and intratumoral HGF concentrations was found; however, the removal of the primary tumor clearly decreased the serum HGF level, suggesting that the elevation of HGF in the serum was tumor related. Twenty-nine (82.9%) of 35 patients with recurrent breast cancer had an increase in the serum HGF level. The HGF level was significantly higher in patients with liver metastases compared to those with other sites of metastases. Postoperative sequential examinations confirmed that the increase in the serum HGF level was associated with the appearance of relapse. In conclusion, the serum HGF level was significantly increased in breast cancer patients. Circulating HGF might play important roles in tumor progression in this malignancy.

Adult↗

Involvement of protein-tyrosine kinase p72syk in collagen-induced signal transduction in platelets.

Previous studies have demonstrated that activation of platelets by collagen results in a dramatic increase in tyrosine phosphorylation of several cellular proteins, including pp125FAK, through the interaction of collagen with integrin alpha 2 beta 1 (GP Ia-IIa). In this study, we report that p72syk is a potential candidate for the protein-tyrosine phosphorylation event following collagen stimulation in porcine platelets. Washed platelets were stimulated with collagen and the activation of p72syk was assessed in an immunoprecipitation kinase assay. The activity of p72syk increased within 1 min, reached a maximum at 5 min after stimulation by collagen, and the phosphorylation at tyrosine residues of p72syk in platelets also occurred in the same time course as the activation of p72syk. Prior treatment of platelets with cytochalasin D to inhibit actin polymerization, or with aspirin and apyrase to inhibit the secondary reaction, or EGTA and the acetoxymethyl ester of 5,5'-dimethyl-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid to chelate both extracellular and intracellular Ca2+, did not affect the activation of p72syk induced by collagen. Furthermore, herbimycin A, a potent protein-tyrosine-kinase inhibitor, was capable of reducing collagen-evoked p72syk activation, Ca2+ mobilization and platelet aggregation. These results suggest that upon stimulation by collagen p72syk is physically activated by a process that is independent of the effects of Ca2+, ADP, and actin polymerization, and may participate in the regulation of Ca2+ mobilization mediated by collagen in platelets.

Animals↗

Preparation of high-molecular-weight DNA: application to mycobacterial cells.

A method for isolating high-molecular-weight DNA from bacteria is described. A special feature of the method is the treatment of whole bacterial cells with an organic solvent (chloroform-methanol (2:1, v/v) or ethanol-ether (1:1, v/v)) prior to DNA extraction from the cells. The DNA preparations obtained from organic solvent-pretreated bacterial cells such as Mycobacterium smegmatis, M. phlei, and Escherichia coli contained highly polymerized DNA, as revealed by pulse-field gel electrophoresis. The size and yield of the DNA obtained from E. coli pretreated with the organic solvent were quite similar to that of the DNA obtained from protoplasts. The results strongly suggest that the organic solvent pretreatment is effective for extracting very large DNA from bacterial cells and especially from bacteria whose protoplasts cannot be easily formed.

DNA, Bacterial↗

The endogenous substrate of low molecular weight acid phosphatase in the brain is an epidermal growth factor receptor.

We have recently reported that low molecular weight (LMW) acid phosphatase, which is supposed to possess phosphotyrosine protein phosphatase activity, showed a significant decrease of activity in Alzheimer brains compared to control brains [Ann. Neurol., 33 (1993) 616-621]. In the present study, we investigated the endogenous substrate of LMW acid phosphatase in the brain. LMW acid phosphatase was purified from bovine brain, and the enzyme was obtained with both a high specific activity and a good yield. The bovine brain enzyme was a monomer with a molecular mass of 17 kDa. We used a specific monoclonal anti-phosphotyrosine antibody to detect phosphotyrosine protein in rat brain extracts. The LMW acid phosphatase from bovine brain dephosphorylated a M(r) 170 kDa phosphotyrosine protein in rat brain extracts. This M(r) 170 kDa protein was considered to be the epidermal growth factor (EGF) receptor using a specific antibody. These results suggest that LMW acid phosphatase in the brain may regulate EGF receptor-dependent transmembrane signalling by dephosphorylating the phosphorylated receptor.

Acid Phosphatase↗