Biomedical subjects

Kazuhiro Suzuki

Publications and source records attributed to Kazuhiro Suzuki.

At least 37 records · Page 2Linked to original sources

PubMed2005

Administration of extract of mushroom Phellinus linteus induces prostate enlargement with increase in stromal component in experimentally developed rat model of benign prostatic hyperplasia.

OBJECTIVES: To clarify the effect of the mushroom extract Phellinus linteus on noncancerous prostate cells using an experimentally developed rat benign prostatic hyperplasia model. A growing number of people take some natural herbal extracts for maintenance of their health. Among them, the extracts of certain mushrooms are believed to have a marked tumoricidal effect but low toxicity for normal tissues, and they are being drunk widely in Japan and Korea. However, until now, their effect on noncancerous benign prostate growth has not been examined. METHODS: The mushroom extract was administered daily for 5 weeks to experimentally developed benign prostatic hyperplasia rats. Prostate organ weight, histologic composition, and gene expression levels of sex hormone receptors, transforming growth factor-beta, vascular endothelial growth factor, and endothelial nitric oxide synthase were examined. RESULTS: Prostate weight increased significantly by 37% owing to treatment with the mushroom extract (P < 0.05). In particular, the stromal component of the prostate increased significantly by 80% (P < 0.05). A suppression of transforming growth factor-beta1 expression by 56% was observed with the mushroom extract treatment (P < 0.05). CONCLUSIONS: We found that the mushroom extract enlarged the prostate. The effect was suggested to be on the prostate stroma, which may be involved in transforming growth factor-beta1 regulation. Administration of mushroom extract should be considered carefully by those with an enlarged prostate.

Agaricales↗

PubMed2005

Outcomes of shockwave lithotripsy for upper urinary-tract stones: a large-scale study at a single institution.

PURPOSE: We investigated the risk factors having an impact on the achievement of stone-free status and on the success rate, as well as on the likelihood of recurrence, in patients undergoing shockwave lithotripsy. PATIENTS AND METHODS: We evaluated the characteristics and outcomes of 3023 patients (3254 renal units) with upper urinary-tract stones who underwent SWL at the Funabashi Clinic over a 13-year period. We assessed the stone-free and success rates for 2844 patients (3061 renal units) 3 months post-SWL. We also determined the recurrence rate for the 1078 patients (1139 renal units) who had achieved stone-free status at that time. RESULTS: Overall, stone-free status was achieved in 65.1% of patients, and the success rate was 85.7%. There were significant differences in the stone-free rates depending on patient age, history of urolithiasis, and presence of pyuria before SWL, as well as the number, location, size, and composition of the stones. Stones recurred in 326 of 1139 renal units (28.6%) during a mean follow-up of 36 months. The recurrence rates were 7.5%, 24.1%, and 33.0% after 1, 3, 5 years, respectively. Multiple stones, a history of urolithiasis, and stones located in the kidney or both kidneys plus the ureter significantly influenced recurrence. Multivariate analysis demonstrated that multiple stones were most significantly related to recurrence. CONCLUSION: Treatment with SWL has a low morbidity and high effectiveness. The number and location of stones and a history of urolithiasis significantly influence recurrence. Further studies of prophylactic therapy are required, especially for patients with these factors.

Adolescent↗

PubMed2005

Indirubin, a Chinese anti-leukaemia drug, promotes neutrophilic differentiation of human myelocytic leukaemia HL-60 cells.

Indirubin, a purple vegetable dye, is a traditional Chinese medicine for myelocytic leukaemia. Indirubin inhibits cyclin-dependent protein kinases (CDKs) and is present in human urine and serum. When indirubin was present during the neutrophilic differentiation of human myelocytic leukaemia HL-60 cells, it augmented superoxide production triggered by opsonized zymosan (OZ) by the terminally differentiated HL-60 cells. It also augmented the calcium response to OZ stimulation, and HL-60 cell chemotaxis evoked by interleukin-8 (IL-8, CXCL8) and formylpeptide. In addition, indirubin induced marked IL-8 release by the cells during differentiation and the cells differentiated with indirubin had typical neutrophilic properties, deformed nuclei and granules. Use of stable cloned HL-60 cells that contained a reporter vector for monitoring the activity of the transcription factor PU.1, which acts specifically at the stage of promyelocyte differentiation into neutrophils and monocytes, revealed that indirubin has a potent promoting activity on intracellular PU.1. Indirubin enhanced the expression of typical neutrophil proteins, including granulocyte-colony stimulating factor receptor, the beta2-integrin subunit CD18, the NADPH-oxidase subunit p47phox, and the IL-8 receptor CXCR1, all are controlled by PU.1. Indirubin also inhibited CDK2-dependent phosphorylation of retinoblastoma protein during neutrophilic differentiation. These results suggest that indirubin augments the neutrophilic differentiation of human myelocytic leukaemia HL-60 cells through inhibition of CDK2 and activation of PU.1.

CD18 Antigens↗

PubMed2005

External Ca2+ dependency of synaptic transmission in drosophila synaptotagmin I mutants.

To resolve some of differences in reports on the function of Synaptotagmin I (Syt I), we re-examined synaptic transmission at the neuromuscular junction of Drosophila embryos that have mutations in the Syt I gene (syt I). Two major questions addressed were which Ca2+ binding domain, C2A or C2B, sense Ca2+ and is Syt I a negative regulator of spontaneous vesicle fusion. Synaptic currents were induced by nerve stimulation or by high K+ treatment in external solutions containing various Ca2+ concentrations. In a null allele, syt I(AD4), synchronous synaptic currents were rarely observed but not abolished. The quantal content was about 1/60 of control but increased linearly with [Ca2+](e) with a slope of 0.95 (N) in the double logarithmic plot, in contrast to 3.01 in control. The slope of 1.06 in an allele, syt I(AD1), which lacks the second Ca2+ binding domain, C2B, was not different from in syt I(AD4). In another allele, syt I(AD3), in which one amino acid in C2B is mutated, synchronous synaptic transmission was also impaired and N was 1.54, which is significantly smaller than in control. In high K+ saline, the [Ca2+](e) dependency of vesicle release in syt I(AD4) was lower than in controls, whereas that in syt I(AD3) was even lower than in syt I(AD4), suggesting that syt I(AD3) is inhibiting vesicle fusion. These findings led us to conclude that C2B, not C2A, senses Ca2+, and Syt I is a negative regulator of vesicle fusion.

Animals↗

PubMed2005

[Prostate biopsy].

Multiple core prostate biopsy was introduced by Eskew et al in 1995, and many procedures of multiple core biopsy were proposed. These methods showed importance of taking samples from lateral part of peripheral zone, transition zone or apex. Cancer detection rates were dramatically increased in comparison with those detected by traditional systematic sextant biopsy (SSB). Utilization of the template, age-volume adjusted parameter or apical horn biopsy facilitated the efficacy of multiple core biopsy. Furthermore, these techniques could contribute to accurate estimation of pathological findings. Multiple core prostate biopsy would get to be more important in modern prostate specific antigen era when more T1c or more early stage prostate cancer would be detected.

Aging↗

PubMed2005

Semaphorin 4A induces growth cone collapse of hippocampal neurons in a Rho/Rho-kinase-dependent manner.

Semaphorins are a family of secreted and membrane-bound proteins, known to control axonal pathfinding. It was recently demonstrated that Semaphorin 4A (Sema4A) is crucially involved in immune cell activation. However, the role of Sema4A in the nervous system has not yet been clarified. To examine if Sema4A can function as a chemo-repulsive cue to growth cones of developing hippocampal neurons, a growth cone collapse assay with recombinant Sema4A was performed in primary hippocampal neurons cultured from E17 mice. In these primary hippocampal neurons, Sema4A induced a significant growth cone collapse as compared with the culture without Sema4A. The Sema4A-induced growth cone collapse could be blocked by Y-27632, a Rho-kinase inhibitor. Furthermore, immunocytochemical analysis with antibodies against Sema4A demonstrated the binding of recombinant Sema4A to the growth cones of hippocampal neurons. Thus, our data indicated that Sema4A could function as a chemo-repulsive cue by activating a receptor whose signal is transmitted to Rho-kinase and induced growth cone collapse of hippocampal neurons.

Animals↗

PubMed2004

Direct regulation of prostate blood flow by vascular endothelial growth factor and its participation in the androgenic regulation of prostate blood flow in vivo.

Previous studies on prostate blood flow regulation have indicated that androgen regulates prostate blood flow. However, the mechanism responsible for this regulation is unknown. In the present study, we focused on the effects of vascular endothelial growth factor (VEGF), a key factor responsible for angiogenesis and androgenic blood flow regulation. We examined in vivo the effect of VEGF on prostate blood flow and its participation in the androgenic regulation of this blood flow using a castrated rat model following subcapsular intraprostatic injection method. We found that VEGF is involved in blood flow regulation with an activity equal to that of dihydrotestosterone (DHT). The effect of VEGF on prostate blood flow was already seen at 30 min after the administration. The elevating effect of DHT on castrated rat prostate blood flow was abolished by coadministration of DHT with neutralizing anti-VEGF antibody. The change in VEGF-A mRNA expression in response to androgen stimulation was examined by double-fluorescent probe quantitative PCR (Taqman PCR). The results showed that androgenic regulation of VEGF gene expression occurred shortly after androgen stimulation. VEGF gene up-regulation was abolished or down-regulated by coadministration of neutralizing anti-VEGF antibody. This is the first report on the importance of VEGF in the androgenic regulation signaling pathway that affects prostate blood flow. Alternative treatment targeted toward anti-VEGF activity as a substitute for ordinary antiandrogenic therapy may be effective against prostate diseases, especially those with androgen-independent and hyperhemorrhagic status.

Androgens↗

PubMed2004

Cumulative probability of PSA increase above 4.0 NG/ML in population-based screening for prostate cancer.

Routine screening for prostate cancer remains controversial. However, it is very important to show how the optimal rescreening interval should be set for men who want to be screened after informed consent. To solve this issue, the risk of prostate-specific antigen (PSA) increase above 4.0 ng/ml relative to baseline PSA levels and age was investigated. Between 1988 and 2000, 7,757 subjects screened twice or more and also with baseline PSA levels of 4.0 ng/ml or lower were enrolled in our study. All serum PSA levels were measured by E-test Tosoh II PA assay at one center. Interval PSA levels for men undergoing screening with a greater than 1 year interval were calculated on the assumption that PSA levels changed over time in a simple exponential fashion. Then, the cumulative rate of freedom from PSA increase above 4.0 ng/ml was estimated using the Kaplan-Meier technique stratified by baseline PSA ranges of 0.0 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 ng/ml and every 10 years of age ranges. Of the 7,757 subjects, 559 (7.2%) were expected to have had PSA levels increase above 4.0 ng/ml within 5 years after the baseline PSA measurements. The cumulative rate of freedom from the PSA increase above 4.0 ng/ml at 5 years was 98.7%, 92.9%, 70.3% and 38.5% in cases of baseline PSA levels of 1.0 ng/ml or lower, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml and 3.1 to 4.0 ng/ml, respectively. The cumulative rates of freedom from the PSA increase were significantly decreased with the baseline PSA ranges being higher regardless of age range. Re-screening interval should be set stratified by baseline PSA levels, regardless of age and race. Rescreening interval should be set at 1, 1 to 2 and 3 to 5 years for men with baseline PSA ranges of 2.1 to 4.0 ng/ml, 1.1 to 2.0 ng/ml and 0.0 to 1.0 ng/ml, respectively, in individual-based screening. In mass screening system using PSA alone, rescreening interval should be set in the same manner as in individual-based screening, except for men with baseline PSA levels of 1.1 to 2.0 ng/ml, which should be set at 1 year to avoid developing incurable prostate cancer.

Aged↗

PubMed2004

Efficacy of intravenous immune globulin therapy combined with dexamethasone for the initial treatment of acute Kawasaki disease.

UNLABELLED: We studied the effects of a new regimen consisting of intravenous immune globulin (IVIG) combined with dexamethasone (DEX) on clinical outcome and serum levels of vascular endothelial growth factor (VEGF) in the initial treatment of Kawasaki disease (KD). A total of 46 KD patients received 0.3 mg/kg per day DEX plus heparin i.v. for 3 consecutive days, together with 2 g/kg IVIG over 4 to 5 days (DEX group). Low-dose acetylsalicylic acid was started after completion of DEX therapy. The control group consisted of 46 KD patients retrospectively treated earlier with 2 g/kg IVIG over 4 to 5 days plus higher dose acetylsalicylic acid (CONTROL group). No serious adverse effect was noted in either group. There were no differences in baseline and post-treatment laboratory data except for C-reactive protein between the groups. Post-treatment C-reactive protein in the DEX group (median 0.9 mg/dl, range 0.0 to 24.7 mg/dl) was lower than that (1.2 mg/dl, range 0.2 to 19.5 mg/dl) in the CONTROL group ( P=0.033 by Mann-Whitney U test). In addition, the mean duration of fever after the first IVIG infusion was 2.2 days (median 1 day, range 1 to 12 days) in the DEX group and 2.8 days (2 days, 1 to 16 days) in the CONTROL group ( P=0.015 by Mann-Whitney U test). The new regimen did not reduce VEGF levels. Two patients in each group developed small- or medium-sized coronary artery aneurysms. CONCLUSION: Although this regimen did not affect coronary outcome, intravenous immune globulin therapy combined with dexamethasone for the initial treatment of Kawasaki disease was safe and may accelerate the resolution of systemic inflammation.

Acute Disease↗

PubMed2004

Modulation of phenotype of human prostatic stromal cells by transforming growth factor-betas.

BACKGROUND: We investigated the effects of transforming growth factor (TGF)-betas on morphological and receptor phenotypes, as well as proliferation of four currently established human prostatic myofibroblast cell lines and one commercially available prostatic stromal cell line. METHODS: The effects of TGF-betas on morphological changes and proliferation of the cells were studied by immunohistochemistry and bromodeoxyuridine assay, respectively. The expression of alpha 1-receptor subtypes was measured by real time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and the radioligand binding assay for the receptors was also performed. RESULTS: TGF-betas 1, 2, and 3 induced expression of desmin and myosin of cells of the established cell lines, and significantly inhibited their growth. The alpha 1a-receptor was expressed only in the commercially available cell line and alpha 1b and 1d, in all cell lines. TGF-beta 1 suppressed the expression of all three subtypes of the alpha 1-receptor. The binding sites of cells of all the cell lines were reduced by treatment with this growth factor. CONCLUSIONS: TGF-betas may induce human prostatic stromal cells to express the smooth muscle phenotype and inhibited their growth. However, the growth factor reduced the binding sites of the receptor and suppressed mRNA expression of its subtypes, suggesting that morphological and receptor phenotypes may be regulated via more than one pathway by TGF-beta(s).

Cell Division↗

PubMed2004

The inhibitory NK cell receptor CD94/NKG2A and the activating receptor CD94/NKG2C bind the top of HLA-E through mostly shared but partly distinct sets of HLA-E residues.

The human non-classical MHC class I molecule HLA-E is a ligand for both an inhibitory NK cell receptor (CD94/NKG2A) and an activating receptor (CD94/NKG2C). To identify HLA-E surface recognized by both receptors, especially to determine if both receptors recognize the same epitope, we made a series of individually Ala-substituted HLA-E proteins and analyzed their binding to CD94/NKG2A orCD94/NKG2C. Eight HLA-E mutations that significantly impaired HLA-E binding to CD94/NKG2A are all found in the top of alpha1/alpha2 domain of HLA-E. These results suggest that CD94/NKG2A binds a HLA-E surface equivalent to a NKG2D binding site on MICA. Of the eight mutations that impaired HLA-E binding to CD94/NKG2A, six significantly impaired HLA-E binding to CD94/NKG2C suggesting that CD94/NKG2C also binds a similar surface of HLA-E. Unexpectedly, the two HLA-E mutations (D69A and H155A) selectively abrogated HLA-E binding to CD94/NKG2A, not largely affected CD94/NKG2C. These results indicate that a mostly shared, but partly distinct set of HLA-E residues is discriminated by the two receptors.

Amino Acid Sequence↗

PubMed2004

Diagnostic significance of PSA density adjusted by transition zone volume in males with PSA levels between 2 and 4ng/ml.

OBJECTIVE: To investigate the diagnostic significance of prostate-specific antigen (PSA), density (PSAD), and PSAD adjusted by transition zone volume (PSATZD) in men with PSA levels between 2.1 and 4.0ng/ml. METHODS: Between 1993 and 2000, 69 men with PSA levels between 2.1 and 4.0ng/ml underwent transrectal ultrasonography (TRUS) and 8-core prostate biopsy. Diagnostic accuracies for various cut-offs of PSAD and PSATZD were investigated according to subdivided PSA levels of 2.1 to 3.0ng/ml and 3.1 to 4.0ng/ml. RESULTS: The detection rate of prostate cancer was 21.7% (15/69). The percentage of patients with extracapsular disease was 33.3% (5/15) and primary Gleason grade 4 or 5 was obtained in 4 (26.7%) patients. The transition zone volume and PSATZD in cancer cases were significantly different in comparison with those in non-cancer cases. The area under the receiver operating characteristic curve for PSATZD was significantly higher in comparison with that for PSAD in the same subdivided PSA ranges. The diagnostic efficiency for PSATZD was higher than that for PSAD. The diagnostic efficiency showed the highest value at the cut-off level for PSATZD of 0.23 and 0.28 in men with PSA levels of 2.1 to 3.0ng/ml and 3.1 to 4.0ng/ml, respectively. CONCLUSIONS: The use of PSATZD cut-offs as a biopsy indication may reduce many unnecessary biopsies without missing most prostate cancer cases in the PSA range of 2.1 to 4.0ng/ml.

Adult↗

PubMed2004

Comparative study on the prevalence of clinically detectable prostate cancer in patients with and without bladder cancer.

OBJECTIVES: To investigate the prevalence of prostate cancer in patients with a past or present history of bladder cancer compared with age-matched control subjects in population-based screening for prostate cancer. METHODS: Between 1998 and 2000, 106 patients who were followed up in the outpatient clinic for bladder cancer (case cohort) and 1060 age-matched men who participated in screening for prostate cancer (control cohort) were enrolled in this study. Serum prostate-specific antigen (PSA) levels were measured for all participants, and all participants underwent digital rectal examination (DRE). The PSA distribution and prevalence rate of prostate cancer were compared between these two cohorts. RESULTS: The serum PSA levels were significantly greater in the case cohort than in the control cohort. The detection rate of prostate cancer was 12.3% (13 of 106) and 1.5% (16 of 1060) in the case and control cohorts, respectively. The biopsy compliance for those with abnormal PSA and/or DRE findings was significantly lower (31%) in the control cohort than in the case cohort (84%). If all those in the control cohort with abnormal PSA and/or DRE findings had undergone prostate biopsies, another 26 cases of prostate cancer might have been detected. The expected detection rate of prostate cancer in the control cohort was high at 4.0% (42 of 1060); however, this was still significantly lower than that in the case cohort. CONCLUSIONS: Patients with a present or past history of bladder cancer could be a high-risk group for developing or having prostate cancer. Additional studies should be conducted to confirm this.

Adenocarcinoma↗

PubMed2004

Ribosomal protein S18 identified as a cofilin-binding protein by using phage display library.

We previously reported that an actin-binding protein, cofilin, is involved in superoxide production, phagocytosis, and chemotaxis in activated phagocytes through cytoskeletal reorganization. To elucidate the functions of cofilin in greater detail we tried to identify cofilin-binding proteins by using a phage-displayed cDNA library constructed from human brain mRNAs. Several phage clones capable of binding to cofilin were obtained, and the phage with the strongest binding affinity contained the C-terminal half of ribosomal protein S18. To confirm the interaction between the S18 protein and cofilin, we investigated whether cofilin would bind to His-tagged S18 protein immobilized in Ni-NTA-agarose gel. Cofilin and the S18 protein co-eluted with a low pH (4.5) buffer, suggesting that the proteins interact with each other. Preincubation of cofilin with actin abrogated the binding to protein S18, indicating that cofilin interacts with S18 protein at the actin-binding site, and cofilin co-immunoprecipitated with FLAG-tagged S18 protein expressed in COS-7 cells. These results suggest that some cofilin molecules bind the ribosomal S18 protein under physiological conditions.

Actin Depolymerizing Factors↗

PubMed2004

Androgen-dependent blood flow control and morphological changes of the capillaries in rat prostate.

To clarify the effect of androgens on the microcirculation of the prostate, organ blood flow and ultrastructural features of the capillaries were investigated. In the ventral prostate (VP) of adult Wistar rats, organ blood flow was measured using a laser Doppler flowmetry, and the morphological features of the subepithelial capillaries were investigated and their luminal area was measured using transmission electron microscopy and a computed image analyzer at 1, 2, 3, and 7 days after castration, and 2 days after castration and gradational testosterone supplementation. The capillaries of the VP were classified into three types; oval opened (type 1), intermediate (type 2) and collapsed (type 3). Organ blood flow reduced from 40.5 to 27.7 mL/min/100 g (p < 0.0001) and the luminal area of the capillaries reduced from 13.5 to 4.5 microm2 (p < 0.0001) 2 days after castration. These reductions of the blood flow and the luminal area were gradationally prevented by testosterone supplementation. In the morphological features of the capillary, type 1 had rapidly shifted to types 2 and 3 after castration, and the shift of the capillary type was significantly prevented by the testosterone supplementation. These results clearly demonstrated that the androgen-dependent ultrastructural and morphological features in subepithelial capillaries revealed local microcirculatory conditions correlating the organ blood flow changes in VP.

Animals↗

PubMed2004

Augmentation of NK cell-mediated cytotoxicity to tumor cells by inhibitory NK cell receptor blockers.

NK cells monitor expression of MHC class I by inhibitory receptors and preferentially kill cells that lose or down-regulate MHC class I expression. One possible mechanism by which tumor cells evade NK cell killing is continued expression of appropriate MHC class I ligands to engage inhibitory receptors on NK cells. We show here that small-mol.-wt blockers against the mouse inhibitory NK cell receptor Ly49A enhance NK cell killing of such tumor cells. We identified Ly49A-binding peptides by selecting phages with the capacity to bind recombinant Ly49A expressed in Escherichia coli from a phage display random peptide library. The Ly49A-binding peptides could also bind Ly49A expressed on mammalian cells. Importantly, the Ly49A-binding peptides blocked Ly49A recognition of its MHC class I ligands H-2Dd and H-2Dk. Moreover, blockade of Ly49A by the peptides enhanced cytotoxicity of Ly49A+ NK cells towards H-2Dd-expressing tumor cells. These results clearly indicate effectiveness of small-mol.-wt blockers of inhibitory NK cell receptors in enhancing NK cell-mediated killing of tumor cells that are otherwise resistant because of MHC class I expression.

Animals↗

PubMed2004

The risk of rapid prostate specific antigen increase in men with baseline prostate specific antigen 2.0 ng/ml or less.

PURPOSE: We estimated the risk of a rapid prostate specific antigen (PSA) increase in men with a low baseline PSA range of 0.0 to 2.0 ng/ml to investigate the validity of setting a re-screening interval of more than 1 year. MATERIALS AND METHODS: Between 1988 and 1999, 6,252 men with baseline PSA 2.0 ng/ml or less without suspicious findings on digital rectal examination (DRE) and 7,304 with the same baseline PSA who did not undergo DRE at the time of baseline PSA measurement were re-screened. The risks of a PSA increase to 4.1 to 10.0, 10.1 to 20.0 and greater than 20.0 ng/ml were investigated and stratified by re-screening interval, baseline DRE status, and subdivided baseline PSA ranges of 0.0 to 1.0 and 1.1 to 2.0 ng/ml. RESULTS: A total of 28 cases (0.2% of 13,556) of prostate cancer were detected after an average re-screening interval of 3.6 years. High PSA above 10 ng/ml at diagnosis was noted in 5 patients (18%), including 2 with a great PSA increase to 1,928 and 298 ng/ml at re-screening intervals of 4 and 6 years, respectively. CONCLUSIONS: Setting 4 to 5-year re-screening intervals for PSA measurements in men with PSA 1.0 ng/ml or less can decrease the cost of PSA tests without lowering sensitivity. A re-screening interval for PSA measurement should be set annually for men with PSA 1.1 to 2.0 ng/ml to minimize the risk of missing aggressive cancer.

Aged↗

PubMed2004

Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitors III. Effect of ring opening of piperazinone moiety on inhibition.

Compounds containing an ethylenediamine structure in place of the piperazine ring of M55113 (1) and M55551 (2) were synthesized to investigate the effects of a piperazine moiety and evaluated for activity as factor Xa (FXa) inhibitors. Most such compounds, however, exhibited lower activity (1/10-1/100) than that of M55113 and M55551 as FXa inhibitors.

Factor Xa Inhibitors↗