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Biomedical subjects

H Mizoguchi

Publications and source records attributed to H Mizoguchi.

At least 109 records · Page 6Linked to original sources
PubMed1999

Prospective evaluation of prostate cancer detection by prostate-specific antigen-related parameters.

BACKGROUND: The diagnostic value of prostate-specific antigen (PSA) for differentiating prostate cancer from benign prostatic conditions is limited by its lack of specificity. Several PSA-related parameters have been suggested as enhancing the discriminatory power of total PSA values, but their clinical utility should be considered preliminary until established in a prospectively evaluated cohort. METHODS: In a prospective cohort study, results of ultrasound-guided biopsy and/or transurethral resection of the prostate gland were assessed in 706 consecutive Japanese men. The clinical usefulness of total PSA, free PSA, percentage of free PSA, PSA density (PSAD), PSA density for transition zone (PSADT) and gland volume for predicting prostate cancer was investigated using receiver operating characteristic (ROC) curve analysis in 16 different patient subgroups. RESULTS: Overall, 150 of the 706 patients (21.2%) had prostate carcinoma. The ROC curve analysis showed that PSAD and PSADT were more powerful predictors of prostate cancer than total PSA in most of the 16 patient subgroups tested. The improvement in performance was modest, however. No substantial difference was noted between PSAD and PSADT. Total gland volume did not significantly affect the performance of these parameters. The use of a PSAD threshold value of 0.11-10.15 ng/mL per cm3 (or a PSADT value of 0.23-0.27 ng/mL per cm3) would have avoided 24-48% (or, for PSADT, 34-40%) of unnecessary biopsies at the cost of missing 5-10% of detectable cancers in a patient subgroup with intermediate total PSA levels. The performance of free PSA and percentage of free PSA was worse than that of any other test in this study. This may be due to inappropriate handling of sera prior to measurement. CONCLUSIONS: The discriminatory potential of total PSA for predicting prostate cancer was modestly improved by the use of PSAD and PSADT. No substantial advantage of PSADT over PSAD could be demonstrated. Stringent and standardized storage conditions should always be maintained when applying free PSA-related parameters.

Aged↗
PubMed1999

A phase II study employing combination regimens containing KRN8602 in drug-resistant acute myeloid leukemia and acute lymphoblastic leukemia. KRN8602 Leukemia Study Group.

We conducted a phase II multicenter study in order to evaluate the efficacy and toxicity of two combination regimens containing KRN8602 (MX2) for drug-resistant acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). AML was treated with KRN8602, 15 mg/m2 i.v. push for 5 days, and cytarabine (AraC), 100 mg/m2 by 24 h coutinuous infusion for 7 days. ALL was treated with KRN8602, 15 mg/m2 i.v. push for 5 days, vincristine (VCR), 1.4 mg/m2 i.v. push, once weekly, and prednisolone (PSL), 40 mg/m2, 3 h infusion for 5 days. In AML and ALL, the complete remission (CR) rate was 36.4% (16 of 44) and 24.1% (seven of 29), and the overall response rate (CR+PR) was 52.3% (23 of 44) and 51.7% (15 of 29), respectively. Among the 29 relapsed cases of AML, a higher CR rate, 51.7% (15 of 29), was obtained. A high incidence of nausea/vomiting and anorexia was observed, and some patients experienced central nervous system disorders and peripheral neuropathy. There was a low incidence of severe neurotoxicities; all other toxicities were manageable. KRN8602 was found to overcome drug resistance clinically, confirming results based on the preclinical studies. We conclude that KRN8602 is an effective novel anthracycline for drug-resistant acute leukemias.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Pharmacokinetics and pharmacodynamics of bunazosin in patients with renal insufficiency.

The pharmacokinetics and pharmacodynamics of the alpha ( 1 ) -blocker bunazosin were studied in 9 patients with renal insufficiency and 11 healthy control subjects after a single oral administration of 3 mg. Plasma and urinary drug concentrations were determined using high-pressure liquid chromatography. The pharmacokinetic parameters of bunazosin elimination half-life and time to peak level were not statistically significantly affected by renal insufficiency. Peak level and area under the plasma concentration-time curve were significantly increased in patients with renal insufficiency compared with control subjects. In addition, plasma clearance and the apparent volume of distribution were significantly smaller in patients with renal insufficiency than in normal subjects. The urinary excretion of bunazosin was not affected by renal insufficiency. Although the normal subject group was not age matched with the patient group, it has been reported that the pharmacokinetics of bunazosin are not affected by age. These results suggest that hepatic metabolism is decreased in renal insufficiency. Concerning the pharmacodynamic effects, the changes in diastolic blood pressure and heart rate were weak but statistically significantly related to plasma bunazosin concentrations. There was no correlation between systolic blood pressure and plasma bunazosin levels. Hysteresis was observed between plasma drug levels and the pharmacodynamic effects.

Adrenergic alpha-Antagonists↗
PubMed1999

Protective effect of Irsogladine on monochloramine induced gastric mucosal lesions in rats:a comparative study with rebamipide.

AIM:To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH(2)Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotective a ctivity.METHODS AND RESULTS:Oral administration of NH(2)Cl-(120mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs.Both irsogladine (1mg/kg-10mg/ kg,po) and rebamipide (30mg/kg-100mg/kg, po) dose dependently prevented the development of these lesions in response to NH(2)Cl, the effect of irsogladine was significant at 3mg/kg or greater, and that of rebamipide only at 100mg/kg. The protective effect of irsogladine on NH(2)Cl induced gastric lesions was significantly reduced by N( G) nitro L arginine methyl ester (L-NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indomethacin but not by L-NAME. Topical application of NH(2)Cl-(20mM)caused a marked reduction of potential difference (PD) in exvivo stomachs. This PD reduction was not affected by mucosal application of irso-gladine, but significantly prevented by rebamipide. The mucosal exposure to NH(4)OH (120mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH(4)OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L-NAME sensitive manner.CONCLUSION:These results suggest that (1)NH(2)Cl gen-erated either exogenously or endogenously damages the gastric mucosa, (2)both irsogladine and rebamipide protect the stomach against injury caused by NH(2)Cl,and (3)the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins.

Journal Article↗
PubMed1999

[Implication of two additional lateral peripheral zone biopsy in the detection of prostate cancer].

BACKGROUND: Despite the strenuous efforts in improving detection of prostate cancer, no standard technique for prostatic biopsy has been established to date. Extended tissue sampling in peripheral zone may possibly lead to enhanced prostate cancer detection. METHODS: Four hundred thirty-three candidates for ultrasound-guided prostatic biopsy were alternately assigned to two groups regarding biopsy techniques between January 1997 and June 1998, Group A, sextant biopsy group and Group B, two additional lateral peripheral zone sampling after standard sextant biopsy. The outcomes of prostatic biopsy were compared. RESULTS: Cancer detection rates were 19.2% (43/217) in Group A and 18.5% (40/216) in Group B. No statistically significant difference was noted (p > 0.05). Clinical stage, Gleason score and the presence of metastasis did not differ significantly between groups (p > 0.05). The incidence and duration of hematuria, hematospermia were essentially the same between groups (p > 0.05). High fever due to possible bacteremia developed only in Group B patients (p = 0.04). CONCLUSIONS: Routine use of additional peripheral zone biopsy is not recommended owing to the equivalent cancer detection rates between groups. The application of additional biopsy should be determined carefully since this may lead to increased incidence of serious complications.

Aged↗
PubMed1999

[Laparoscopic radical nephrectomy for renal cell carcinoma--transperitoneal anterior approach].

PURPOSE: To evaluate the usefulness of transperitoneal anterior approach in laparoscopic radical nephrectomy for patients with renal cell carcinoma. MATERIAL: Ten patients (Eight males and two females) with small renal cell carcinoma less than 7 cm in diameter were treated with laparoscopic radical nephrectomy between June 1997 and May 1999. Clinical stage was T1aN0M0 in 6 cases and T1bN0M0 in 4 cases. METHOD: Of the 10 patients, the initial four received preoperative embolization of the renal artery. Under general anesthesia laparoscopic radical nephrectomy via transperitoneal anterior approach was performed in all patients. This procedure facilitates initiated early access to the renal vessels as does open radical nephrectomy. The kidney was dissected en bloc with Gerota's fascia and delivered from the small skin incision without morcellation. RESULT: Two patients needed conversion to open surgery. The mean operating time of eight patients except for conversion cases was 247 minutes and the mean blood loss was 258 ml. There was no major complication associated with laparoscopic procedure. CONCLUSION: Transperitoneal anterior approach in laparoscopic radical nephrectomy is a suitable and useful procedure for the treatment of small renal cell carcinoma because it enables us to avoid possible tumor manipulation by early access to the renal vessels as open radical nephrectomy.

Adult↗
PubMed1999

[Thrombopoietin: current and future status].

Thrombopoietin (TPO), which is a major physiological regulator of platelet production, was cloned in 1994. It has already been shown that the administration of recombinant TPO increases platelet production and accelerates platelet recovery after cytoablative therapy in preclinical and clinical trials. In addition, recent results indicate that the effects of TPO on hematopoiesis are more widespread than initially anticipated. In this article, physiological activities of TPO and results of clinical trials are briefly reviewed, and possible clinical application and some problems in its clinical use are discussed.

Animals↗
PubMed1999

[Phase I clinical study of SH L573 (fludarabine phosphate) in patients with chronic lymphocytic leukemia and adult T-cell leukemia/lymphoma].

We have conducted a phase I clinical study of fludarabine phosphate, a new purine nucleoside derivative, in patients with chronic lymphocytic leukemia and adult T-cell leukemia/lymphoma. The patients were given intravenous administration at a dose of 15 mg/m2/day followed by 20 mg/m2/day and 25 mg/m2/day, each dose given consecutively for 5 days. The dose limiting factors were thrombocytopenia and neutropenia. The thrombocyte count and neutrocyte count dropped to their lowest value in week 1 to 2 after administration, but the changes were reversible, and these counts recovered in most patients. The maximum tolerated dose of the study drug was 25 mg/m2/day, and it was decided to administer 20 mg/m2/day as the recommended dose for the subsequent phase II clinical study.

Adult↗
PubMed1999

A prospective randomized trial of KRN8602 and cytosine arabinoside vs. daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. The KRN8602 Leukemia Study Group.

A prospective randomized study was conducted to compare the efficacy and toxicity of two anthracyclines for the treatment of patients with acute myelogenous leukemia (AML). Fifty-eight patients were randomized and received induction therapy consisting of cytosine arabinoside (AraC) 100 mg/m2/day for 7 days combined with either KRN8602 (3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride [KRN]) 15 mg/m2/day for 5 days (KRN/AraC group) or daunorubicin (DNR) 40 mg/m2/day for 3 days (DNR/AraC group). Complete remission rate was 78.6% (22/28) in the KRN/AraC group and 73.1% (19/26) in the DNR/AraC group. There was a higher incidence of nausea/vomiting and anorexia observed in the KRN/AraC group compared to the DNR/AraC group, while the incidence of other adverse effects (stomatitis, diarrhea, and infectious complications) were similar between both groups. No electrocardiogram (ECG) abnormalities were observed after treatment in the KRN/AraC group, while in the DNR/AraC group, one patient showed ECG abnormality and three patients exhibited either arrhythmia, heart failure, or tachycardia. Mental disorder was reported in two cases in the KRN/AraC group. These findings suggest that KRN/AraC is similar in effectiveness to DNA/AraC but more toxic in central nervous system and gastrointestinal symptoms and less toxic regarding cardiac function in patients with previously untreated AML.

Adolescent↗
PubMed1999

Ecotropic viral integration site-1 is activated during, and is sufficient for, neuroectodermal P19 cell differentiation.

Expression of the ecotropic viral integration site-1 (Evi1) proto-oncogene during murine embryonal development is observed by in situ hybridization in primary head folds and neural crest-derived cells associated with the peripheral nervous system and embryonic mesoderm. To elucidate whether expression of Evi1 is involved in early neuroectodermal or mesodermal differentiation, we used murine embryonal carcinoma P19 cells as a model for the study of early embryonic differentiation. After retinoic acid (RA) treatment with aggregation, expression of Evi1 was detected during neural differentiation in P19 cells. However, Evi1 was not expressed in P19 cells during mesodermal differentiation after DMSO treatment with aggregation. Enforced expression of Evi1 in P19 cells induced neuron-specific microtubule-associated protein-2 microtubule-associated protein-2 and TrkA expression in the absence of RA under monolayer culture. After incubation with RA with aggregation, the Evi1 clones expressed microtubule-associated protein-2 continuously but did not express glial fibrillary acidic protein as an astrocyte marker protein until 12 days of culture. Thus, the overexpression of Evi1 leads to neural differentiation of P19 cells and blocks further differentiation into astrocytes by RA treatment, suggesting that Evi1 might be an important transcription factor for regulation of early neuroectodermal differentiation.

Animals↗
PubMed1999

Dual action of nitric oxide in pathogenesis of indomethacin-induced small intestinal ulceration in rats.

We investigated the pathogenic role of nitric oxide (NO) in indomethacin-induced intestinal ulceration in rats. Nonfasting animals responded to a single administration of indomethacin (10 mg/kg, s.c.), resulting in multiple hemorrhagic lesions in the small intestine, mostly the jejunum and ileum. The damage was first observed 6 hr after indomethacin, the severity increasing progressively with time up to 24 hr later, accompanied with the gene expression of inducible NO synthase (iNOS) and the increase of nitrite and nitrate (NOx) contents in the mucosa. The ocurrence of damage was significantly prevented when iNOS induction was inhibited by dexamethasone given either once 0.5 hr before or twice 0.5 hr before and 6 hr after indomethacin. Likewise, aminoguanidine (a relatively selective iNOS inhibitor) reduced the severity of damage, irrespective whether given twice or as a single injection 6 hr after indomethacin. By contrast, the non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) exhibited a biphasic effect, depending on the time of administration; the pre-administration worsened the damage, while the later administration reduced the severity of these lesions, yet both responses occureed in a L-arginine-sensitive manner. Pre-administration of L-NAME, but not aminoguanidine, significantly decreased NOx production in the intestinal mucosa of normal rats, while the increase of NOx production following indomethacin was significantly suppressed by the later administration of aminoguanidine as well as L-NAME. These results suggest that NO exerts a dual action in the pathogenesis of indomethacin-induced intestinal ulceration; NO generated by cNOS is protective against indomethacin, by maintaining the integrity of intestinal mucosa, while NO derived by iNOS plays a key pathogenic role in the ulcerogenic process.

Animals↗
PubMed1999

Evidence for viability of coccoid forms of Helicobacter pylori.

It is an open question whether the coccoid form of Helicobacter pylori is alive in the dormant state or is degenerative and in the process of cell death. We studied the viability of the coccoid form of H. pylori to explore the possibility of infectivity to the host by evaluating its protein synthesis and acid response. Coccoid H. pylori conserved the capability to produce proteins for at least 100 days when stored at 4 degrees C in either phosphate-buffered saline (PBS) or distilled water. After 20 days of storage in distilled water exposure of the coccoids obtained to acidic pH induced expression of the several proteins but inhibited those induced after 20 days of storage in PBS. However, after extending the incubation of the coccoid forms in PBS up to 100 days, the organisms acquired the ability to induce the proteins in response to acid stress. The induction of protein expression may be involved in the biological event of transformation into the spiral form. Furthermore, this altered response of the coccoids to acid shock may determine the potential for morphological reversion during incubation.

Bacterial Proteins↗
PubMed1999

[Phase II clinical study of SH L 573 (fludarabine phosphate) in patients with chronic lymphocytic leukemia].

We conducted a multicenter phase II clinical study of fludarabine phosphate, a new purine nucleotide analogue, in patients with chronic lymphocytic leukemia (CLL). Fludarabine phosphate was administered at a dose of 20 mg/m2/day intravenously for 5 days every 4 weeks as one course. Six courses as a maximum were repeated. The response rate was 38.5% (95% confidence intervals: 20.2% to 59.4%), with 1 complete remission and 9 partial remissions out of 26 treated patients. Major drug-related adverse reactions were fever, nausea, weakness, and paresthesia of the fingers; as a grade-3 reaction, varicella was also reported. Neutropenia and thrombocytopenia were observed as manifestations of hematologic toxicity. Clinical laboratory test results revealed abnormalities in hepatic function, including increased GPT, but none of these was rated grade 3 or 4.

Adolescent↗
PubMed1998

Chromosome band 1p36 contains a putative tumor suppressor gene important in the evolution of chronic myelocytic leukemia.

Chronic myelocytic leukemia (CML) is a common neoplasm of hematopoietic pluripotent stem cells. Although the evolution from chronic phase to blast crisis (BC) in CML patients is an inevitable clinical feature, little is understood about the mechanisms responsible for the transformation. We have previously performed allelotype analysis in CML BC and have detected frequent loss of heterozygosity (LOH) on the short arm of chromosome 1. To know the common region of LOH where a putative tumor suppressor gene may reside, deletional mapping was performed using 33 microsatellite markers spanning chromosome 1 in 30 patients with CML BC (21 myeloid and 9 lymphoid). DNA was extracted from slides of bone marrow smears or from bone marrow mononuclear cells. In each patient, DNA from chronic phase was analyzed alongside DNA from either their BC or accelerated phase. Allelic loss on 1p was observed in 14 of the 30 individuals (47%): 10 of the 21 myeloid and 4 of the 9 lymphoid BC cases. Serial cytogenetic information was available in 10 cases with LOH on 1p; interestingly, deletions in this region were not detected. Two samples showed LOH at all informative loci on 1p, whereas the other 12 samples showed LOH on at least one but not all loci on 1p. The common region of LOH resided proximal to D1S508 and distal to D1S507 (1p36). Our results suggest that a tumor suppressor gene that frequently plays an important role in the evolution to BC resides on 1p36 in CML.

Adult↗
PubMed1998

Antisense oligodeoxyribonucleotide against the MLL-LTG19 chimeric transcript inhibits cell growth and induces apoptosis in cells of an infantile leukemia cell line carrying the t(11;19) chromosomal translocation.

To clarify the role of the multiple lineage leukemia gene-leukemia translocation gene of chromosome 19 (MLL-LTG19) protein in leukemogenesis, we synthesized antisense oligodeoxyribonucleotide (ODN) against the fused region of the MLL-LTG19 chimeric transcript and treated KOCL33 cells carrying the t(11;19) translocation with antisense ODN. The antisense ODN inhibited cell growth and induced apoptosis in KOCL33 cells but not in Daudi cells, which have no t(11;19). The levels of MLL-LTG19 mRNA and MLL-LTG19 protein in KOCL33 cells treated with antisense ODN were shown to decrease with time by reverse transcription-PCR and Western blot analysis. These results suggest that the MLL-LTG19 fusion protein contributes to cell proliferation and malignant transformation in infantile acute leukemia cells carrying the t(11;19) translocation.

Apoptosis↗
PubMed1998

Characterization of endomorphin-1 and -2 on [35S]GTPgammaS binding in the mouse spinal cord.

In the present study, G-protein activation by newly-isolated opioid peptides, endomorphin-1 and -2, was examined in the mouse spinal cord by monitoring the binding of the non-hydrolyzable analog of GTP, guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS). Both endomorphin-1 and -2 increased [35S]GTPgammaS binding to mouse spinal cord membranes in a concentration-dependent and saturable manner and reached a maximal stimulation of 57.3+/-5.0 and 60.2+/-3.2%, respectively, at 10 microM. In contrast, the synthetic selective micro-opioid receptor agonist [D-Ala2,NHPhe4,Gly-ol]enkephalin (DAMGO) had a much greater efficacy and produced 103.4+/-5.4% of the maximal stimulation. The receptor specificity of endomorphin-stimulated [35S]GTPgammaS binding was verified by co-incubating membranes with endomorphins in the presence of specific micro-(beta-funaltrexamine and D-Phe-Cys-D-Tyr-Om-Thr-Pen-Thr-NH2 (CTOP)), delta-(naltrindole) or K-(nor-binaltorphimine) opioid receptor antagonists. Co-incubation with either beta-funaltrexamine or CTOP blocked both endomorphin-1- and-2-stimulated [35S]GTPgammaS binding in a concentration-dependent manner, whereas neither naltrindole nor nor-binaltorphimine had any effect on the [35S]GTPgammaS binding stimulated by either endomorphin-1 or -2. The data presented indicate that either endomorphin-1 or -2 activate G-proteins by specific stimulation of micro-opioid receptors, and may act as partial agonists with moderate catalytic efficacies in the mouse spinal cord.

Animals↗
PubMed1998

Growth inhibition by overexpression of human DEAD box protein rck/p54 in cells of a guinea pig cell line.

We transfected cells of a guinea pig cell line with RCK cDNA inserted in a pIRES1neo expression vector. The overexpression of rck/p54 was confirmed by Western blot and RT-PCR analysis. In two clones expressing rck/p54, the cell growth was highly inhibited; and their anchorage-independent growth, which is an important character of malignant transformation, was not found. These findings are the first evidence that the overexpression of a DEAD box protein/RNA helicase could inhibit substantially cell growth at the translational level.

Animals↗