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Biomedical subjects

N Nagai

Publications and source records attributed to N Nagai.

At least 91 records · Page 5Linked to original sources
PubMed1998

Plasma levels of 5-HT and 5-HIAA increased after intestinal ischemia/reperfusion in rats.

Intestinal ischemia/reperfusion (I/R) causes serious systemic injury, mainly from a variety of bioactive substances released from the injured intestine. To assess the possible roles of serotonin (5-hydroxytryptamine, 5-HT), a bioactive amine mainly stored in the intestine, in I/R injury, we assayed the levels of tryptophan, 5-HT, and 5-hydroxyindole acetic acid (5-HIAA) in the blood and intestine in a rat I/R model. Plasma 5-HT increased significantly over time after reperfusion; the plateau level was obtained 4 h after reperfusion and was associated with an increase in 5-HIAA. Plasma tryptophan levels declined gradually after reperfusion. The ratio of 5-HIAA/5-HT was significantly higher in I/R rats than in control rats, suggesting that elevated 5-HT was quickly metabolized in the systemic circulation. In the intestine, 5-HT decreased dramatically, whereas tryptophan increased. This phenomenon was prominent in the severely damaged intestine. These findings suggest that the injured intestine released large amounts of 5-HT, whereas its synthesis in the injured intestine was suppressed. An increase in 5-HT in the circulation may be related to various circulatory disturbances observed in humans after intestinal ischemia.

5-Methoxytryptamine↗
PubMed1998

pH and carbonate levels in developing enamel.

Our earlier studies showed that the surface of developing and calcifying enamel changes its pH alternatively along the tooth axis when stained with pH indicating dyes. Based on the pH conditions, the enamel at this stage was distinguished as neutral zone (N1 and N2) and acid zone (A1 and A2). The aim of the present study was to correlate changes of pH with proteolytic activity and crystal size of the calcifying bovine enamel. Specimens of developing bovine enamel were separated into four maturing stages using pH staining methods. Crystal chemistry of the developing enamel was investigated using thermogravimetry (TGA), ICP emission spectrometry, X-ray diffractometry (XRD) and infrared spectroscopy (IR). Previous biochemical analysis of proteolytic enzyme activity from enamel indicated that the optimal pH of the major protease was approximately pH 6.0, coinciding with the pH of the A1 zone. IR, TGA and XRD analyses showed that most of the organic components of the enamel decomposed at 580 degrees C. Higher levels of carbonate were observed in the secretory stages than in mature enamel. The Ca/P molar ratio of the enamel apatite was lower than the stoichiometric value of 1.67. These results suggest that growth and maturation of enamel apatite crystals is related to a decrease in the carbonate level and appear to be related to the alternative calcification and decomposition of enamel proteins.

Ameloblasts↗
PubMed1998

[Telomerase activity and telomere length as diagnostic tumor marker for ovarian tumors].

Telomerase activity was detected in germ cells, stem cells and cancer cells. In tumors of the ovary, an organ that contains germ cells, the authors examined availability to detect telomerase activity. Telomerase activity of malignant tumors was extremely high compared with that of normal ovaries and benign tumors. Strength and frequency of telomerase activity in malignant tumors was significant different from that in benign tumors. Telomere length tended to be smaller for malignant tumors of advanced stage, but no significant relationship between telomere length and telomerase activity and tumor stage could be recognized. Telomerase activity may be a useful marker for the diagnosis of ovarian tumors.

Biomarkers, Tumor↗
PubMed1998

Human thrombin and calcium bound factor Xa significantly shorten tPA-induced fibrin clot lysis time via neutralization of plasminogen activator inhibitor type 1 activity.

Employing a fibrin clot lysis assay, we reassessed the significance of the neutralization of plasminogen activator inhibitor type 1 (PAI-1) activity by thrombin and factor-Xa in fibrinolysis. When PAI-1 enriched fibrin clots were formed using increasing concentrations of thrombin (0.1, 0.5, 1.0 IU/ml), their lysis times became shorter (43.8 +/- 4.9, 25.7 +/- 3.7, 13.9 +/- 0.8 h respectively). Times were shortened further by either heparin (43.9 +/- 11.0, 12.1 +/- 2.6, 3.6 +/- 0.2 h respectively) or vitronectin (17.0 +/- 1.6, 1.9 +/- 0.7, 0.9 +/- 0.0 h respectively). Factor-Xa together with Ca++ shortened the clot lysis time further. Fibrin autography revealed that both enzymes dose dependently interfered with complex formation between tPA and PAI-1, making large amounts of tPA remaining to be free form. The mechanism seems to play a role in the coagulation associated enhancement of fibrinolysis.

Anticoagulants↗
PubMed1998

[Bellini duct carcinoma of the kidney: a case report].

A case of Bellini duct carcinoma is reported. A 71-year-old woman visited our hospital with a chief complaint of lower abdominal pain. Computerized tomography, ultrasonography showed a mass lesion measuring about 5 cm in the right kidney. Angiography showed an avascular mass lesion in the right kidney. Right radical nephrectomy was performed under the diagnosis of renal cell carcinoma. Histological examinations showed Bellini duct carcinoma of the papillary type. We performed M-VAC (methotrexate, vinblastine, doxorubicin, icisplatin) therapy as is used for transitional cell carcinoma. She is alive with no evidence of disease 5 months after her surgical treatment. To our knowledge, only 32 cases of Bellini duct carcinoma have been reported in the Japanese literature.

Aged↗
PubMed1998

[Postoperative complications after Mainz pouch construction--with emphasis on measures to deal with narrowing of the duct aperture].

Thirty patients underwent Mainz pouch construction between December 1992 and January 1998. The post-operative observation period varied from 6 to 57 months (average, 38.5 months). A mechanism to ensure urinary continence was provided in 24 cases, while formation of a nipple valve by intussusception of the ileum with seromuscular stripping and submucosally embedded in situ appendix was performed in 6 cases. An umbilical stoma was adopted in all cases. Late-phase complications included 3 cases of hydronephrosis requiring treatment. Efferent limb of the stoma was observed in 8 cases, 6 of which were attributable to mild constriction of the stoma at the site of anastomosis of the navel cavity. In those cases in which stomal stricture occurred, difficulty in withdrawing urine was eliminated by providing a fistula stopper. Although few clinical methods to deal with stomal stricture have been reported, we found the fistula stopper to be useful providing good external appearance and patients' quality of life.

Adult↗
PubMed1998

[Histopathological examination of transurethral electrovaporization of the prostate].

Transurethral electrovaporization of the prostate (TVP) has been devised to eliminate prostatic tissue by electric vaporization and to create a dry coagulation layer beneath to minimize bleeding from the site of TVP. However, vaporization induces degeneration due to thermal coagulation deep in the tissue beneath the vaporized layer, and local tissue damage is thus greater than that caused by the standard transurethral resection of prostate (TURP) loop. Since this results in difficulty with histopathological examination, the percentages of tissue-diagnosable area were determined in sections resected using various vaporization electrodes (Roller Loop, Band & Wedge Loop). The percentage of tissue-diagnosable area was 92.0 +/- 3.3% with the standard TUR loop, 2.4 +/- 0.9% with the Roller Loop, 42.7 +/- 21.1% with the Band Loop, and 39.7 +/- 24.4% with the Wedge Loop. Concerning speed of resection, the best vaporization effect was obtained when the speed of operation was 1/2 or 1/3 that with the standard TUR loop. Since the region in which tissue diagnosis was smaller with the vaporization electrode than with standard TURP, more careful examination was required for diagnosis of incidental cancers. Therefore, postoperative observation by PSA measurement appeared to be important.

Aged↗
PubMed1997

Telomerase activity in ovarian tumors.

BACKGROUND: Shortening of telomeres occurs with each cell division and eventually results in cell death. The activity of telomerase, an enzyme that catalyzes telomere elongation, has been detected in germ cell lines and cancer cells, and has been detected in immortal cell lines but not in normal somatic cells. The relationship between telomerase expression and ovarian carcinogenesis was investigated. METHODS: Ovarian tissue was obtained from 41 women with ovarian tumors (10 benign, 6 borderline-malignant, and 25 malignant tumors) and 6 with uterine disease (2 with uterine myoma and 4 with uterine carcinoma). These specimens were analyzed for telomerase activity and telomere length by the telomeric repeat amplification protocol and Southern blot hybridization, respectively. RESULTS: Telomerase activity was detected in 23 of 25 malignant ovarian tumors (92%), in 1 of 6 borderline-malignant tumors (16.7%), and in 2 of 10 benign tumors (20%) (both of which were germ cell tumors). Weak telomerase activity was present in the cortex of normal ovaries from premenopausal women, and appeared to be attributable to follicles. Telomerase activity in malignant and poorly differentiated tumors tended to be higher than that in other tumors. Terminal restriction fragment length ranged between 8 and 13 kilobase pairs (kbp) for normal ovaries, and was <8 kbp in 1 of 6 malignant Stage I tumors (16.7%), 1 of 2 Stage II tumors (50%), and 9 of 17 Stage III tumors (52.9%). CONCLUSIONS: Telomerase activity may be a useful marker for the diagnosis of ovarian tumors.

Adult↗
PubMed1997

Quantitative relationship between pharmacokinetics of unchanged cisplatin and nephrotoxicity in rats: importance of area under the concentration-time curve (AUC) as the major toxicodynamic determinant in vivo.

PURPOSE: The major pharmacokinetic parameters of unchanged cisplatin (CDDP) related to nephrotoxicity were evaluated in rats in vivo using a pharmacodynamic model. METHODS: CDDP was administered according to various dosing schedules (single bolus, intermittent bolus, or continuous infusion). Unchanged CDDP in plasma and urine was quantified using high-performance liquid chromatography (HPLC). The pharmacokinetics were assessed by model-independent methods. The relationship between pharmacokinetics and BUN levels was evaluated using a sigmoid maximum response (Emax) model. RESULTS: Unchanged CDDP showed linear pharmacokinetics after single bolus injections of 1 to 5 mg/kg CDDP. Nephrotoxicity was ameliorated following intermittent bolus injection (1 mg/kg per day for 5 days) and continuous infusions (over 2 and 3 h) of the same CDDP doses (5 mg/kg), although these dosing schedules did not change the area under the concentration-time curve (AUC), total clearance (Clt), urinary excretion of unchanged CDDP or kidney platinum levels significantly. The maximum BUN level, as a nephrotoxicity marker, showed dose-related increases after single bolus injection of 1 to 5 mg/kg CDDP and after 3-h infusion of 5 to 25 mg/kg. The pharmacodynamic relationship between the maximum BUN level and Cmax and between the maximum BUN level and AUC were apparently different between single bolus injection and 3-h infusion. The maximum BUN level was related to the AUC calculated by plasma concentrations of unchanged CDDP greater than the threshold level (AUC > Cmin), a relationship most successfully described by the signoid Emax model, regardless of CDDP dose and schedule. The plasma threshold level of unchanged CDDP was determined as 0.9 microgram Pt/ml in rats. CONCLUSIONS: The present results substantiated the importance of C x T (AUC) value as an indicator of CDDP-induced nephrotoxicity in vivo as well as of tumor cell-killing effect of CDDP in vitro. The AUC > Cmin of unchanged CDDP was found to be an important pharmacokinetic parameter predicting CDDP nephrotoxicity.

Animals↗
PubMed1997

Verruciform xanthoma of the oral mucosa: an immunohistochemical and ultrastructural study of two cases.

Verruciform xanthoma is an uncommon benign lesion of unknown aetiology and pathogenesis. Two cases of verruciform xanthoma are presented together with an immunohistochemical and ultrastructural study. One case co-occurred with an odontogenic keratocyst which, to our knowledge, has not been previously reported, and another case occurred on masticatory mucosa with an asymptomatic, granular, exophytic lesion causing a cleft-like gingival recession. In an immunohistochemical study using antibodies to macrophage (CD 68[KP1]), alpha-1-antitrypsin, vimentin, desmin, keratin, neuron-specific enolase (NSE) and S-100 protein, the characteristic foam cells of verruciform xanthoma showed strong positive staining for CD 68[KP1] and vimentin and weak positive staining for alpha-1-antitrypsin, while the other antibodies were negative. As in previous studies, S-100 protein positive dendritic cells were detected in lesional connective tissue. In addition, the ultrastructural findings revealed characteristics of macrophages containing varying sized lipid vacuoles and degenerating epithelial cells. These findings support the concepts that the foam cells in verruciform xanthoma are of monocyte-macrophage lineage and that the epithelial degeneration from uncertain causes may be related to the pathogenesis of the lesion.

Adult↗
PubMed1997

Structural characterization of the molten globule and native states of ovalbumin: a 1H NMR study.

Molecular characteristics of ovalbumin (OVA) in the acidic (pD 3.08, the E-form) and neutral [pD 7.29, the N-form (native form)] regions were studied by measuring effective radii, 1H NMR spectra, spin-echo 1H NMR spectra and cross-relaxation times (TIS) from irradiated to observed protein protons which are particularly sensitive for detection of the mobile segments and/or structural looseness in proteins. 1H NMR spectra did not show significant differences between the N- and E-forms except for the spectral lines in the CH3, epsilon CH2 and aromatic regions. Effective radii and TIS values for main- and side-chains showed 1.08 and 1.5- to 2.0-fold increases on going from the N- to E-forms, respectively. The elongation of TIS values might indicate the appearance of the fluctuating tertiary structure in the E-form. Molecular characteristics of the E-form, inferred from reported far ultraviolet-circular dichroism (UV-CD) spectra in the peptide region, near UV-CD spectra in the aromatic region [Koseki et al. (1988) J. Biochem. 103, 425-430], effective radii and especially elongation of TIS values might indicate that the E-form could be in the molten globule state. The onset of denaturation of OVA using TIS measurements was also studied.

Animals↗
PubMed1997

Little or no response to 24-hr water-deprivation of Fos-like immunoreactivity in vasopressinergic magnocellular neurons in the hypothalamus of hereditary microphthalmic rats.

In normal rats, 24-hr water-deprivation was found to cause a significant increase in the plasma concentration of arginine vasopressin (AVP), and marked induction of Fos in the AVP-positive magnocellular neurons in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus. On the other hand, 24-hr water-deprivation also caused a significant increase in the plasma AVP concentration in hereditary microphthalmic rats, but much less than in normal rats. Consistent with this, the extent of induction of Fos in the nuclei of the PVN and SON of these rats was lesser than in normal rats. These results suggest that hereditary microphthalmic rats have a defect or decrease in the response to water-deprivation of vasopressinergic magnocellular neurons in the PVN and SON.

Animals↗
PubMed1997

Fibrinolytic parameters as an admission prognostic marker of head injury in patients who talk and deteriorate.

Because it has been difficult to predict the outcome of patients with head injury in the early period after admission, a clinical study was undertaken to evaluate if the fibrinolytic parameters could be reliable indicators of outcome. Seventy patients presenting with head injury without obvious trauma in other regions were studied, and plasma levels of alpha2-plasmin inhibitor-plasmin complex (PIC) and D-dimer on admission (within 2 hours postinjury) were assessed. Plasma levels of both PIC and D-dimer were elevated and correlated well to patient outcomes. When plasma PIC levels were higher than 15 microg/ml or D-dimer levels were higher than 5 microg/ml, 92% of patients died regardless of their consciousness level on admission, whereas all patients made good recoveries when their PIC levels were less than 2 microg/ml or D-dimer levels were less than 1 microg/ml. Therefore, plasma levels of both PIC and D-dimer on admission were revealed to be reliable prognostic markers of head injury. Using these markers, patients with poor outcomes (progressive brain injury), such as "talk and deteriorate" types, could be readily identified on admission.

Adolescent↗
PubMed1997

Expression of CD44 alternative splicing variants in primary and lymph node metastatic lesions of gynecological cancer.

CD44 is known as an adhesion molecule which is involved in lymphocyte activation and lymphocyte homing. In recent years, its role in the invasion and metastasis of malignant tumors has attracted the attention of investigators. In this study, the expression of CD44 variants was investigated in primary lesions and metastasis into the lymph node in 53 patients with gynecological cancer. The following patients with various types of gynecological carcinoma, established by operation and pre-treatment biopsy, were included in this study: 19 patients with cancer of the uterine cervix, 23 with cancer of the uterine endometrium, and 11 with ovarian cancer. Tissue samples were obtained from a primary lesion and a nodal metastasis of each patient, and immunohistochemical staining was performed by the ABC method through the use of monoclonal antibodies against CD44v1-10. Specimens proving CD44v1-10 positive were then submitted to immunohistochemical staining through the use of monoclonal antibodies against CD44v6 and CD44v9. Expression of CD44v was judged positive when DAB revealed color development, irrespective of the degree of staining intensity. CD44v were all expressed in the cancer cell membrane. In normal endometrium, expression of CD44v1-10 and v9 was observed in the endometrial gland cell membrane. In normal ovarian tissues, CD44v6 and v9 were not detected. The expression of CD44v6 in patients with endometrial cancer was noted in 13 (72.2%) of 18 patients with vascular invasion and in one (20.0%) of 5 patients without it, indicating a significant relation to vascular invasion. It was also remarkably higher in those for whom the invasion exceeded 1/2 of the myometrium than in those for whom the invasion did not exceed 1/2 of the myometrium, and was higher too in advanced stages and in node-positive patients. In one patient, CD44v6 was detected not in the primary lesion but in the nodal metastasis. The expression of CD44v6 in patients with ovarian cancer occurred more frequently in node-positive patients. Our study results suggest that the expression of CD44v6 in endometrial adenocarcinoma cells is involved in the progression of the carcinoma, nodal metastasis, myometrial invasion, and vascular invasion, and that in ovarian cancer, the expression of CD44v6 is involved in nodal metastasis.

Alternative Splicing↗
PubMed1997

Interleukin-1 as an autocrine stimulator in the growth of human ovarian cancer cells.

The role of interleukin-1 (IL-1), a multifunctional cytokine which mediates important immune responses, was investigated in the growth of ovarian cancer cell lines in vitro. The messenger RNA for IL-1 alpha and IL-1 beta was expressed in six and four ovarian cancer cell lines, respectively out of eight. Measurement of IL-1 in the eight cell lines by enzyme-linked immunosorbent assay revealed that two lines, MCAS and TYK-nu, secreted a high amount of IL-1 alpha, but that none secreted IL-1 beta after 72 hours of incubation. The growth of these cells was significantly stimulated by the addition of recombinant IL-1 alpha (rIL-1 alpha) in a concentration-dependent manner in a 96 hour culture. The maximum response was obtained with 10 ng/ml of IL-1 alpha by counting the viable cell number using trypan blue. [3H]-thymidine incorporation by these cells was also stimulated by a 72 hour incubation with rIL-1 alpha. The spontaneous growth of these cells was inhibited by the addition of anti-IL-1 alpha antibody, anti-IL-1 receptor antibody or IL-1 receptor antagonist. These cells expressed two classes of IL-1 binding receptors on their surface as detected by [125I]-labeled rIL-1 alpha. These results indicate that IL-1 alpha is an autocrine growth stimulator for some ovarian cancer cells and suggest that IL-1 alpha plays an important role in the progression of this disease.

Antibodies, Monoclonal↗
PubMed1996

The inhibition of human factor Xa by plasminogen activator inhibitor type 1 in the presence of calcium ion, and its enhancement by heparin and vitronectin.

Plasminogen activator inhibitor type 1 (PAI-1), a member of serine proteinase inhibitor superfamily, is known to inhibit thrombin in the presence of either heparin or vitronectin. We analyzed possible inhibitory activity of PAI-1 on human factor Xa. PAI-1 inhibited factor Xa in the presence of calcium ion (Ca2+), whereas no inhibition was observed in the absence of Ca2+. Half maximal enhancement by Ca2+ was obtained at 0.8 mM. An equimolar complex formation between factor Xa and PAI-1 in the presence of Ca2+ was observed by SDS polyacrylamide gel electrophoresis. Both unfractionated heparin and vitronectin enhanced the inhibition only in the presence of Ca2+. Apparent second-order rate constant (ki) for the inhibition of factor Xa by PAI-1 at 5 mM Ca2+ was 1.6 x 10(4) M-1 s-1, and was enhanced 3-fold by 2 u/ml of heparin (4.6 x 10(4) M-1 s-1) and 10-fold by 100 nM vitronectin (1.6 x 10(5) M-1 s-1), respectively. The interaction between Ca(2+)-bound factor Xa and PAI-1 could be important from the view of PAI-1 neutralization and enhancement of fibrinolysis.

Calcium↗
PubMed1996

The in vitro effects of chylomicron remnant and very low density lipoprotein remnant on platelet aggregation in blood obtained from healthy persons.

We investigated the in vitro influence of chylomicron (CM) remnant and very low density lipoprotein (VLDL) remnant on platelet aggregation in healthy persons. The separation of CM and VLDL remnants from serum was performed using an immunoaffinity gel mixture containing anti apo B-100 and anti apo A-1 antibodies coupled to Sepharose 4B. The preincubation with CM and VLDL remnants significantly enhanced the platelet aggregation in whole blood and in platelet rich plasma (PRP) induced by collagen. This effect was observed in whole blood with the addition of VLDL remnant at the concentration of 5 mu g/ml, and in PRP with the addition of CM remnant at the concentration of 1 and 5 mu g/ml, and with the addition of VLDL remnant at the concentration of 5 and 10 mu g/ml. These results may indicate that increase in remnant lipoproteins may be a part of the reasons for atherosclerotic and thrombotic complications.

Antithrombins↗