Biomedical subjects

H Adachi

Publications and source records attributed to H Adachi.

At least 235 records · Page 13Linked to original sources

PubMed1995

The role of cysteine in the alteration of bovine liver dihydrodiol dehydrogenase 3 activity.

Bovine liver NADP(+)-dependent dihydrodiol dehydrogenase (DD3) is extremely sensitive to SH reagents such as N-ethylmaleimide (NEM) and 5,5'-dithiobis(2-nitrobenzoic acid). NEM produced time- and concentration-dependent inactivation of DD3 in a pseudo-first-order reaction manner. This inactivation was prevented by NADP+, 3-acetylpyridine-adenine dinucleotide phosphate, 2',5'-ADP and 2'-AMP but not by substrates, NAD+, nicotinamide mononucleotide or 5'-ADP.DD3 was absorbed by an affinity column of thiopropyl-Sepharose 6B, but enzyme incubated with both NEM and NADP+ was not. Moreover, one [14C]NEM molecule was incorporated into a cysteine of DD3 in the presence, and two cysteines of DD3 in the absence, of NADP+. These results suggested that two cysteine residues were modified per enzyme molecule by NEM, one was protected by NADP+ and the other had no significant function for the enzyme activity. Two radiolabelled peptides (P1 and P2) produced by the digestion with lysyl endopeptidase of [14C]NEM-modified DD3 could be separated by reverse-phase HPLC. P1, which was radiolabelled by [14C]NEM only in the absence of NADP+, showed the following sequence; H2N-Tyr-Lys-Pro-Val-Xaa-Asn-Gln-Val-Glu- NEM.Cys-His-Pro-Tyr-Phe-Asn-Gln-Ser-Lys-COOH (Xaa indicates a possible cysteine residue). This sequence was very similar to that of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase (3 alpha-HSD/DD) (residues 184 to 201) and was also highly conserved in the aldo-keto reductase superfamily. The sequence of P2, which had radioactivity in both the absence and presence of NADP+, also contained an NEM-modified cysteine and was similar in sequence to the regions located in loop A of rat 3 alpha-HSD/DD. The present study suggests that P1, which may have a cysteine residue corresponding to Cys-193 of rat 3 alpha-HSD/DD, functions in the alteration of DD3 activity depending on the modulation of NADP(+)-binding ability through a thiol/disulphide exchange reaction similar to that of rat 3 alpha-HSD/DD shown in our previous results; while P2, which may have a cysteine residue corresponding to Cys-145 of rat 3 alpha-HSD/DD, may be located near the surface of the enzyme molecule.

Amino Acid Sequence↗

PubMed1995

Enzymatic characterization of a novel bovine liver dihydrodiol dehydrogenase--reaction mechanism and bile acid dehydrogenase activity.

Bovine liver cytosolic dihydrodiol dehydrogenase (DD3) has been characterized by its unique dihydrodiol dehydrogenase activity for trans-benzenedihydrodiol (trans-1,2-dihydrobenzene-1,2-diol) with the highest affinity and the greatest velocity among three multiple forms of dihydrodiol dehydrogenases (DD1-DD3). It is the first time that DD3 has shown a significant dehydrogenase activity for (S)-(+)-1-indanol with low Km value (0.33 +/- 0.022 mM) and high K(cat) value (25 +/- 0.79 min-1). The investigation of the product inhibition of (S)-(+)-1-indanol with NADP+ versus 1-indanone and NADPH clearly showed that the enzymatic reaction of DD3 may follow a typical ordered Bi Bi mechanism similar to many aldo/keto reductases. Additionally, DD3 was shown to catalyze the dehydrogenation of bile acids (lithocholic acid, taurolithocholic acid and taurochenodeoxycholic acid) having no 12-hydroxy groups with low Km values (17 +/- 0.65, 33 +/- 1.9 and 890 +/- 73 microM, respectively). In contrast, DD1, 3 alpha-hydroxysteroid dehydrogenase, shows a broad substrate specificity for many bile acids with higher affinity than those of DD3. Competitive inhibition of DD3 with androsterone against dehydrogenase activity for (S)-(+)-1-indanol, trans-benzenedihydrodiol or lithocholic acid suggests that these three substrates bind to the same substrate binding site of DD3, different from the case of human liver bile acid binder/dihydrodiol dehydrogenase (Takikawa, H., Stolz, A., Sugiyama, Y., Yoshida, H., Yamamoto, M. and Kaplowitz, N. (1990) J. Biol. Chem. 265, 2132-2136). Considering the reaction mechanism, DD3 may also play an important role in bile acids metabolism as well as the detoxication of aromatic hydrocarbons.

Animals↗

PubMed1995

Evaluation of exercise capacity using submaximal exercise at a constant work rate in patients with cardiovascular disease.

BACKGROUND: Symptom-limited incremental exercise tests are used to estimate the severity of cardiovascular disease and the patient's daily activity. However, there is a need for objective parameters for submaximal exercise. To test the hypothesis that a decrease in maximal exercise capacity can be estimated by oxygen uptake (VO2) kinetics, we measured the time constant of VO2 both during the onset of constant work rate exercise at 50 W and during recovery from this exercise and compared it with data obtained during maximal exercise in patients with cardiovascular disease and in normal subjects. METHODS AND RESULTS: A total of 34 patients with cardiovascular disease and 14 normal subjects performed 6 minutes of 50-W constant work rate exercise and an incremental exercise test to the symptom-limited maximum on a cycle ergometer. VO2 was calculated from respiratory gas analysis on a breath-by-breath basis. The time constant of VO2 during the onset of 50-W exercise was 61.4 +/- 15.2 seconds in patients with cardiovascular disease, significantly longer (the kinetics of VO2 were slower) than that in normal subjects (48.8 +/- 10.4 seconds, P = .008). The time constant of VO2 during the onset of exercise was significantly negatively correlated with peak VO2 (r = -.67) and maximal work rate (r = -.66). The time constant during recovery, which did not differ significantly from that of exercise, was also prolonged in patients with cardiovascular disease; it showed a negative correlation with peak VO2 (r = -.63) and maximum work rate (r = -.54). CONCLUSIONS: The time constant of VO2 during and after recovery from 50 W of constant work rate exercise, which does not require the subject's maximal effort, is a useful and objective measure of exercise capacity in patients with mild to moderate cardiovascular disease.

Adult↗

PubMed1995

Chinese hamster ovary cells expressing a novel type of acetylated low density lipoprotein receptor. Isolation and characterization.

Macrophage scavenger receptors mediate the recognition of a wide range of negatively charged macromolecules including acetylated low density lipoproteins (AcLDL). Chinese hamster ovary (CHO) cells were cultured in the presence of increasing concentrations of simvastatin, a cholesterol biosynthesis inhibitor, and AcLDL as the sole source of exogenous lipoproteins. The cells surviving under these conditions specifically bound 125I-labeled AcLDL with high affinity and degraded them via an endocytic pathway. Unexpectedly, the association and degradation of 125I-labeled AcLDL by these CHO cells were not inhibited by dextran sulfate, fucoidan, and polyinosinic acid, competitors of macrophage scavenger receptors, but were completely inhibited by maleylated bovine serum albumin. Furthermore, these cells effectively took up negatively charged liposomes containing acidic phospholipids such as phosphatidylserine and phosphatidic acid, whereas CHO cells expressing macrophage scavenger receptors did not. AcLDL and negatively charged liposomes were cross-competed with each other. Northern blot analysis using the cDNA for the macrophage scavenger receptor revealed that these CHO cells did not express this receptor. From these observations, we conclude that the isolated CHO cells express a novel type of AcLDL receptor, which is distinct from macrophage scavenger receptors with respect to ligand specificity and competitor sensitivity.

Albumins↗

PubMed1995

1H-, 13C-, and 113Cd-NMR study of the Cd(II) complex of a blocked peptide, Z-Cys-Ala-Pro-His-OMe, in organic solvents.

The Cd(II) complex of a peptide, Z-Cys-Ala-Pro-His-OMe was prepared and characterized by absorption, CD, 1H-, 13C-, and 113Cd-nmr, and nuclear Overhauser effect spectroscopy (NOESY) spectra to show the coordination of cysteine thiolate and histidine imizazole to Cd(II) ion. The NOESY spectra in dimethyl formamide showed that the cysteine residue was in proximity to the histidine residue. These results reveal the chelation of Z-Cys-Ala-Pro-His-OMe to Cd(II) ion in solution. Temperature-dependent dissociation equilibrium of histidine imidazole in solution was observed in this complex. Structural features of the chelating peptide are discussed.

Amino Acid Sequence↗

PubMed1995

Human herpesvirus-6 infection in renal allografts: retrospective immunohistochemical study in Japanese recipients.

This study was conducted to determine the incidence and clinical significance of human herpesvirus-6 (HHV-6) infection in renal allografts. A total of 105 biopsy specimens from 72 recipients were immunohistochemically examined for the presence of HHV-6 antigen, which localized in the distal tubular epithelial cells and in a few lymphocytes infiltrating into the interstitium. HHV-6 antigen in the tubular epithelia was detected in 63 (61.2%) specimens. Categorically, a higher incidence of the antigen was noted in specimens of accelerated rejection (3/4, 75.0%), acute rejection (28/3, 73.7%), and cyclosporin nephropathy (8/11, 72.7%). The antigen was present and absent an almost equal number of times in the categories of chronic rejection, intraoperative and routine protocol biopsies. Repeated biopsies were performed in six cases showing HHV-6 antigen, only one of which underwent transplant nephrectomy due to severe chronic rejection. Single or multinucleated giant cells in distal tubuli occurred in 10 (9.5%) specimens in a scattered manner. All of them were diagnosed as acute or chronic rejection. The giant cells showed no immunoreactivity for HHV-6, cytomegalovirus, or herpes simplex virus. These results indicate overall that HHV-6 infection is common in renal allografts and might be reactivated in acute rejection or cyclosporin nephropathy. The presence of HHV-6 antigen, however, does not necessarily correlate with a poor prognosis for the renal graft nor with the occurrence of giant cells in distal tubuli.

Adult↗

PubMed1995

Left ventricular end-systolic volume index in patients with ischemic cardiomyopathy predicts postoperative ventricular function.

BACKGROUND: We investigated the usefulness of the preoperative left ventricular end-systolic volume index (LVESVI) as a predictor of postoperative ventricular function. METHODS: We retrospectively reviewed the records of 310 patients who underwent coronary artery bypass grafting and identified 20 patients with ischemic cardiomyopathy with a preoperative ejection fraction less than 0.30. We determined the preoperative and postoperative ejection fraction, LVESVI, and left ventricular enddiastolic volume index using biplane left cineventriculography. Patients were divided into groups depending on whether their preoperative LVESVI was less than 100 mL/m2 (group A, n = 10) or greater than 100 mL/m2 (group B, n = 10). RESULTS: The mean ejection fraction increased significantly after coronary artery bypass grafting in group A from 0.25 +/- 0.05 to 0.40 +/- 0.09 (p < 0.01), but did not change significantly in group B (0.26 +/- 0.05 versus 0.23 +/- 0.06). The mean LVESVI decreased significantly in group A from 83.2 +/- 13.7 to 61.7 +/- 20.4 mL/m2 after operation (p < 0.05), but did not change significantly in group B (124.7 +/- 21.0 versus 121.5 +/- 37.6 mL/m2). In group B, 4 patients had signs of congestive heart failure during the follow-up period and had to be rehospitalized. CONCLUSIONS: The mean ejection fraction improved significantly after coronary artery bypass grafting in patients with a preoperative LVESVI less than 100 mL/m2, despite the presence of a global left ventricular ejection fraction less than 0.30. Our results suggest that the preoperative LVESVI predicts the postoperative status and left ventricular function in patients with ischemic cardiomyopathy.

Aged↗

PubMed1995

Interleukin-8 and monocyte chemotactic activating factor responses to cardiopulmonary bypass.

Cardiac operations with cardiopulmonary bypass cause a systemic inflammatory response. Neutrophils and monocytes-macrophages play an important role in triggering the initiation of the inflammatory response. Recently, some kinds of cytokines that are powerful leukocyte chemotactic factors have been characterized concerning an inflammatory response: interleukin-8 has a potent chemoattractant activity for neutrophils, and monocyte chemoattractant factor has monocyte-macrophage chemotactic activity. To investigate the possible roles of the cytokines in the inflammatory response in cardiopulmonary bypass, 12 adult patients undergoing cardiopulmonary bypass were studied for measurement of interleukin-8 and monocyte chemoattractant factor. Systemic blood was collected before cardiopulmonary bypass, at the end of cardiopulmonary bypass, and at 3, 12, 24, and 48 hours after cardiopulmonary bypass from the patients' radial arteries. Significant increases in levels of interleukin-8 and monocyte chemoattractant factor were detected with a peak level at 3 hours after bypass compared with levels before cardiopulmonary bypass (p < 0.05). This study demonstrated that interleukin-8 and monocyte chemoattractant factor are released into the circulation after adult hypothermic cardiopulmonary bypass and reach a maximum level 3 hours after bypass.

Aged↗

PubMed1995

IV compared with brachial plexus infusion of butorphanol for postoperative analgesia.

In a randomized, double-blind, controlled study, we have compared two groups of patients receiving either continuous systemic i.v. or continuous brachial plexus infusion of butorphanol for analgesia after operations on the upper extremities. Twenty-two patients undergoing elective upper extremity surgery were allocated randomly to one of two groups to receive either butorphanol i.v. and saline injected into the brachial plexus sheath (i.v. group) or butorphanol injected into the brachial plexus sheath and saline i.v. (brachial plexus group). After surgery on the upper extremity under continuous axillary brachial plexus block, each patient received a continuous infusion of butorphanol either i.v. or into the brachial plexus sheath at a dose of 83.3 micrograms h-1. Concurrently, a saline infusion was given via the alternate route. Patients rated their pain on a 10-cm visual analogue scale (VAS). VAS scores in the two groups did not differ up to 6 h and 24 h after operation. From 9 h until 24 h after operation, pain scores were significantly higher in the i.v. group than in the brachial plexus group. The VAS score 9 h after operation was 3.3 (SD 2.7) in the i.v. group and 0.6 (0.9) in the brachial plexus group (P < 0.01); 12 h after operation 2.7 (1.8) in the i.v. group and 0.6 (0.9) in the brachial plexus group (P < 0.01); 18 h after operation 1.7 (1.0) in the i.v. group and 0.7 (1.0) in the brachial plexus group (P < 0.05); and 24 h after operation 3.2 (2.4) in the i.v. group and 0.7 (1.2) in the brachial plexus group (P < 0.01). We conclude that continuous injection of butorphanol into the brachial plexus sheath provided superior analgesia compared with continuous i.v. injection.

Adolescent↗

PubMed1995

Comparison of continuous brachial plexus infusion of butorphanol, mepivacaine and mepivacaine-butorphanol mixtures for postoperative analgesia.

We have reported recently that continuous administration of butorphanol into the brachial plexus sheath provided analgesia of a quality superior to that of continuous i.v. administration. In the present study, we have compared postoperative pain relief produced by continuous infusion of one of three types of solution into the axillary sheath: opioid alone, local anaesthetic alone or a mixture of local anaesthetic and opioid. In patients undergoing upper extremity surgery with continuous axillary brachial plexus block, we injected one of the three solutions into the axillary neurovascular sheath: butorphanol 2 mg (group B), 0.5% mepivacaine alone (group M) and 0.5% mepivacaine-butorphanol (group MB); the volume of each solution was 50 ml, administered at a rate of 50 ml per 24 h. At 3 h after operation, visual analogue scale (VAS) scores were significantly higher in group M than in group MB (P < 0.01), and higher in group B than in group MB (P < 0.05).

Adolescent↗

PubMed1995

Expression and function of fibronectin binding integrins on rat mast cells.

Adhesion molecules of the integrin family are implicated not only in leukocyte migration but also in leukocyte activation. Here we characterize the expression and function of fibronectin receptor integrins on rat mast cells. A rat basophilic leukemia cell line (RBL-2H3) and phorbol ester-stimulated rat peritoneal mast cells adhered to fibronectin (FN), vitronectin and fibrinogen. These mast cells expressed fibronectin receptor integrins, including very late antigen (VLA)-4, VLA-5 and vitronectin receptor (VNR), as estimated by immunofluorescent staining and inhibition of FN adherence by newly established mAbs reactive with the rat alpha 4 (MR alpha 4-1), alpha 5 (HM alpha 5-1) or beta 3 (HM beta 3-1) chains of the integrin molecules. The beta-hexosaminidase release, a marker for mast cell degranulation, triggered by high affinity IgE receptor (Fc epsilon RI)-mediated stimulation, was enhanced by adhesion of RBL-2H3 cells to either immobilized FN, MR alpha 4-1, HM alpha 5-1 or HM beta 3-1. This FN enhancement of beta-hexosaminidase release was inhibited by soluble MR alpha 4-1, HM alpha 5-1 and HM beta 3-1 as well as by GRGDSP and DELPQLVTLPHPNHLGPEILDVPST peptides which abrogate VLA-5/VNR and VLA-4 binding to FN respectively. In vivo, passive cutaneous anaphylaxis induced by IgE anti-DNP and DNP-BSA was inhibited by concurrent s.c. injection of MR alpha 4-1, HM alpha 5-1 and HM beta 3-1. These results demonstrate that FN receptor integrins expressed on rat mast cells play an important role in regulating mast cell activation both in vitro and in vivo.

Amino Acid Sequence↗

PubMed1995

Cloning and expression of dipeptidase from Acinetobacter calcoaceticus ATCC 23055.

The gene encoding dipeptidase was cloned from Acinetobacter calcoaceticus ATC 23055. Determination of the nucleotide sequence revealed that the gene had an open reading flame of 1,050 bp coding a protein of 350 amino acids. The deduced amino acid sequence showed 48.8% similarity to human renal dipeptidases and conserved two amino acid residues identified in human and pig renal dipeptidases as essential ones for the catalytic activity. Purified recombinant enzyme expressed in Escherichia coli did not hydrolyze the unsaturated dipeptide, glycyldehydrophenylalanine. On the other hand, it preferentially hydrolyzed dipeptides having a D-amino acid, when compared with those having an L-amino acid at the C-terminal. Furthermore, it could not hydrolyze tripeptides. These results indicate that the dipeptidase produced by A. calcoaceticus ATC 23055 has a unique substrate specificity and preferentially hydrolyzes dipeptides having a D-amino acid at the C-terminal.

Acinetobacter calcoaceticus↗

PubMed1995

Changes in epidermal growth factor receptor and the levels of its ligands during menstrual cycle in human endometrium.

We examined menstrual cycle-dependent changes in the expression of human endometrial epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and epidermal growth factor receptor (EGFR) and their mRNA using immunoblot analysis, 125I-EGF binding, and competitive reverse transcription and polymerase chain reaction (RT-PCR). We also studied their localization in the endometrial tissue by immunohistochemistry. Endometrial samples were obtained at three stages of menstruation: the early follicular stage, which exhibits low serum estradiol (E2) and progesterone (P) levels; the late follicular stage, which exhibits high E2 and low P levels; and the luteal stage, which exhibits high E2 and P levels. Immunohistochemical examination showed that EGF, TGF alpha, and EGFR were localized to the endometrial epithelium. Immunoblot analysis revealed that endometrial EGF, TGF alpha, and EGFR levels were significantly (p < 0.01) increased at the late follicular and luteal stages compared to the early follicular stage. 125I-EGF-specific binding levels at the late follicular and luteal stages were significantly (p < 0.01) higher than at the early follicular stage, consistent with the results of immunoblot analysis. Competitive RT-PCR revealed that EGF, TGF alpha, and EGFR mRNA levels were significantly (p < 0.01) higher at the late follicular and luteal stages than at the early follicular stage. Changes in EGF, TGF alpha, and EGFR mRNA levels were consistent with changes in protein levels. These findings suggest that synthesis and expression of human endometrial EGF, TGF alpha, and EGFR vary with the stage of the menstrual cycle and that their expression in the human endometrium is associated with the increase in the serum E2 but not with the increase in P levels.

Binding, Competitive↗

PubMed1995

Implication of nitric oxide synthase in carcinogenesis: analysis of the human inducible nitric oxide synthase gene.

Nitric oxide (NO) is a newly identified, multifunctional biological mediator. However, it also has deleterious effects on biological materials. For instance, nucleic acids, proteins, and some prosthetic groups of enzymes can be modified by NO or its reaction products with other reactive oxygen species. Endogenous nitrosamine formation through the reaction of NO or its oxidized products with amines might be involved in carcinogenesis. These deleterious effects of NO are often associated with inflammatory processes both in experimental animals and human. We analyzed the molecular mechanism of control of expression of the inducible nitric oxide synthase (NOS) gene in mouse cells by cloning its putative promoter region. This promoter responded to various cytokines and endotoxin similarly to the endogenous NOS gene in mouse cells. No appreciable induction of NOS was observed in human peripheral blood cells, but induction was detected in a human glioblastoma cell line A-172. Therefore, the human inducible NOS cDNA was cloned from A-172 cells and its cDNA-deduced amino acid sequence found to have about 80% similarity to those of both mouse and rat inducible NOSs. The effects of various cytokines on the induction of the gene were somewhat different from those observed in mouse cells, but the mouse promoter responded to these cytokines similarly to the endogenous NOS gene in human cells, indicating functional similarity of cis-elements of the genes encoding both human and mouse inducible NOS. Structural analysis of the human inducible NOS gene by Southern blot analysis revealed putative genetic restriction fragment length polymorphism in intron 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Prevention of restenosis after coronary angioplasty with low-density lipoprotein apheresis.

A prospective study was performed to determine whether low-density lipoprotein (LDL) apheresis, when performed only immediately before and after percutaneous transluminal coronary angioplasty (PTCA), is effective in preventing restenosis of coronary artery lesions following PTCA. Thirty-six patients with coronary heart disease (CHD) and hypercholesterolemia were divided into 2 groups. The 9 patients in the LDL group underwent LDL-apheresis 1 day before and 5 days after PTCA while the 27 patients of the control group underwent PTCA but did not undergo LDL-apheresis. Follow-up coronary angiography (CAG) was performed 4 months after PTCA. The rate of restenosis of coronary artery lesions was significantly lower in the LDL group (0%) than in the control group (30%). These findings suggest that LDL-apheresis, when performed before and after PTCA, is effective in preventing restenosis of coronary artery lesions in patients with CHD and hypercholesterolemia.

Aged↗

PubMed1995

Evaluation of the antithrombogenicity of a new microdomain structured copolymer.

A new antithrombogenic material was studied, fluorine-acryl-styrene-urethane-silicone (FASUS) copolymer, the theoretical basis of which attributed to its hydrophilic and hydrophobic microdomain structure. In this series of experiments, the blood compatibility of this copolymer was evaluated in vitro and ex vivo. For the in vitro evaluation, a whole blood clotting test and the microsphere column test were performed. For the ex vivo evaluation, two series of shunt tests in rabbits were performed, one was the arterioartery (A-A) shunt model, and the other was the arteriovenous (A-V) shunt model. The antithrombogenicity was assessed by measuring the shunt obstructive time in the A-A shunt experiment. The A-V shunt experiment was assessed by measuring the circulating platelet counts, platelet aggregability, activated partial thromboplastin time (APTT), and prothrombin time (PT). In the whole blood clotting test, FASUS revealed the significantly longer blood clotting time than that of the control glass tubings (19.7 +/- 1.0 versus 6.5 +/- 0.7 min, p < 0.001). In the microsphere column test, the coated group had a 30% reduction of the platelet number in the eluted blood in contrast with a marked decrease of 70% in the control group (p < 0.05). In the ex vivo A-A shunt experiment, the occlusion time for the FASUS-coated group was significantly longer than that of the control (109.7 +/- 17.3 versus 3.0 +/- 0.4 min, p < 0.05). The A-V shunt experiment showed that the FASUS copolymer suppressed the decrease in platelet counts and tended to improve prolonged APTT compared with that of the control. Clinically, in 25 patients, we placed coated FASUS copolymer into the cannulas for use in percutaneous cardiopulmonary support (PCPS) procedures. There was no evidence of thrombus on the blood contacting surface and no thromboembolism in major organs clinically or upon postmortem examination. In summary, this new copolymer may be effective in preventing thrombus formation in vitro, ex vivo, and in clinical situations.

Aged↗

PubMed1995

Serum N-acetyl-beta-D-glucosaminidase activity in predicting the development of hypertension.

We conducted a prospective study in residents of a small farming community in southwestern Japan to determine whether elevated serum N-acetyl-beta-D-glucosaminidase (NAG) activity would predict future hypertension. The 505 normotensive subjects (blood pressure, < 140/90 mm Hg; mean age, 52 +/- 12 years) were reexamined after 7 years; 111 (22%) had become hypertensive (defined as blood pressure > or = 140/90 mm Hg and/or taking antihypertensive medication at follow-up). After adjustment for age and sex, the development of hypertension was significantly related to body mass index (P < .002), the sum of skinfolds (P < .001), baseline blood pressure (P < .0001), serum cholesterol (P < .01), serum uric acid level (P < .0001), and serum NAG activity (P < .005). Elevated NAG activity showed an independent relationship to future hypertension (P < .005) after adjustments for age, sex, baseline blood pressure (systolic, diastolic, or mean), uric acid level, and the sum of skinfolds. Therefore, elevated serum NAG activity was an effective indicator of future hypertension, and it might therefore be related to functional and/or structural changes in the cardiovascular system.

Acetylglucosaminidase↗

PubMed1995

Estrogen induces epidermal growth factor (EGF) receptor and its ligands in human fallopian tube: involvement of EGF but not transforming growth factor-alpha in estrogen-induced tubal cell growth in vitro.

We studied the estrogen-dependent expression of epidermal growth factor (EGF), transforming growth factor (TGF) alpha, and EGF receptor gene transcripts in human fallopian tubes in vivo and in vitro. Competitive polymerase chain reaction (PCR) was performed on the fallopian tube RNA samples from the postmenopausal women with or without estrogen replacement. Amounts of EGF, TGF alpha, and EGF receptors gene transcripts in the estrogen-treated group (n = 3) were significantly (P < 0.01) more than those in the untreated group (n = 3). Competitive PCR also showed that EGF, TGF alpha, and EGF receptor gene transcripts level in tubal cells were increased by estrogen in vitro: messenger RNA levels of these factors were significantly (P < 0.01, n = 3) increased in cells incubated with 10(-8) M estrogen compared with those in cells without estrogen treatment. We studied whether EGF and/or TGF alpha is involved in the estrogen-induced tubal cell growth in vitro. Estrogen enhanced the [3H]-thymidine incorporation into the cell in dose- and time-dependent manners in culture: estrogen treatment for more than 12 h significantly (P < 0.05) enhanced the [3H]-thymidine incorporation into the cell at 10(-8) M. The estrogen-induced cell growth was observed in association with the increase in EGF, TGF alpha, and EGF receptor messenger RNA levels by estrogen. If the EGF and/or TGF alpha is involved in the cell growth, then the estrogen-induced cell growth should be suppressed by blocking the action of EGF and/or TGF alpha. Therefore, we examined the effects of neutralizing monoclonal antibodies against EGF, TGF alpha, and EGF receptors. Anti-EGF antibody significantly reduced the estrogen-induced increase in [3H]-thymidine incorporation, whereas anti-TGF alpha antibody failed to show the effect. Anti-EGF receptor antibody showed a significant suppressive effect on the estrogen-induced increase in [3H]-thymidine incorporation. Moreover, the growth inhibitory effect by 1 microgram/ml anti-EGF was restored by 10(-8) M EGF but not by TGF alpha even at 10(-6) M. All these data suggest that estrogen induces EGF and TGF alpha/EGF receptors in the human fallopian tube and that EGF but not TGF alpha may be involved in the estrogen-induced human tubal cell growth in vitro.

Antibodies, Monoclonal↗