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Biomedical subjects

A Fujii

Publications and source records attributed to A Fujii.

At least 73 records · Page 4Linked to original sources

Imbalance between serum matrix metalloproteinase-2 and its inhibitor as a predictor of recurrence of urothelial cancer.

Serum levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) were evaluated as prognostic indicators of the recurrence of urothelial cancer. Sera were obtained from 127 healthy control subjects and 97 urothelial cancer patients who underwent complete resection and were measured for MMP-2 and TIMP-2 using a one-step enzyme immunoassay. The relationship between the serum MMP-2/TIMP-2 ratio and the recurrence of urothelial cancer was examined. The mean serum MMP-2/TIMP-2 ratio in the 31 advanced urothelial cancer patients with recurrence was significantly higher than that in the 22 patients without recurrence (P = 0.0029) and in the 44 superficial bladder cancer patients (P < 0.0001). The 1- and 3-year disease-free survival rates in the patients with high MMP-2/TIMP-2 ratios (50% and 12%) were significantly poorer than those of the patients with normal ratios (82% and 56%) (P = 0.0152). Univariate and multivariate analyses of recurrence demonstrated that the serum MMP-2/TIMP-2 ratio is a significant independent indicator of advanced urothelial cancer. Our results indicate that an imbalance between the serum levels of MMP-2 and TIMP-2 could be a new predictor of recurrence in advanced urothelial cancer patients.

Adult↗

Results of transurethral resection plus adjuvant intravesical chemotherapy for superficial bladder cancer.

BACKGROUND: We analyzed the results of conservative therapy for superficial bladder cancer to determine the risk factors for recurrence and progression. METHODS: Between May 1984 and February 1997, 111 patients with primary superficial bladder cancer were treated by a transurethral resection with or without intravesical instillation of chemotherapy, or for patients with concomitant carcinoma in situ (CIS), bacillus Calmette-Guérin. We examined the relationship between tumor stage, grade, incidence of concomitant CIS and recurrence-free survival according to pathologic findings and the drugs instilled. RESULTS: The incidence of concomitant CIS in pT1, grade 3 tumors was significantly higher than that in pTa, grade 1 tumors (42% vs. 3%, P= 0.006). The 5-year recurrence-free survival rate of all patients was 73%. There was no significant difference in recurrence-free survival and pathologic stage, tumor grade, presence of concomitant CIS, or drugs used for instillation. However, the recurrence-free survival in patients with > or = 5 tumors was significantly lower than in patients with less than 5 tumors. Of the 111 patients, only 3 patients demonstrated disease progression and underwent a radical cystectomy, while 1 patient with a pT1b, grade 3 tumor developed a tumor in the ureter. No patient died of bladder cancer. CONCLUSION: Our results indicate that the prognosis of superficial bladder cancer patients with a high-stage, high-grade (pT1, grade 3) tumor is favorable when treated by a transurethral resection and intravesical instillation. Bacillus Calmette-Guérin therapy is useful to prevent the recurrence of tumors with concomitant CIS.

Administration, Intravesical↗

Optical Monitoring of Cerebral Hemodynamics and Oxygenation in the Neonatal Piglet

> Objective: Optical spectroscopy can monitor changes in cerebral oxyhemoglobin (HbO), deoxyhemoglobin (Hb), and total hemoglobin (HbT = Hb + HbO). The purpose of this study was to identify which one of these three optical variables would be the best correlate of cerebral hemodynamics and oxygenation accompanying different physiological conditions known to affect cerebral perfusion pressure and oxygenation. Methods: Eleven anesthetized and ventilated newborn piglets were subjected to: 1) hyperoxic hypercapnia, 2) asphyxia from room air, 3) hypertension, 4) hypotension, and 5) cerebral venous congestion. Optical measurements were recorded continuously along with carotid blood flow (CaBF) measured by the transit time Doppler technique and arterial hemoglobin oxygen saturation (SaO2) measured by pulse oximetry. Results: A good positive HbT-CaBF correlation was recorded during hypercapnia (r = 0.816), asphyxia (r = 0.846), hypertension (r = 0.72), and hypotension (r = 0.95), where as negative correlation was recorded during venous congestion (r = -0.91). A good positive correlation HbO-SaO2 was recorded during asphyxia (r = 0.842) and hypotension (r = 0.86), whereas no HbO-SaO2 agreement occurred during hypercapnia (r = 0.23), hypertension (r = 0.19), and venous congestion (r = 0.34), when SaO2 did not change at all. A good positive HbO-SaO2 correlation was recorded during hypercapnia (r = 0.84), hypertension (r = 0.91), and hypotension (r = 0.94), suggesting a high HbO dependence on changes in CaBF. Conclusions: We demonstrated that none of the optical variables (Hb, HbO, HbT) alone can be used as a correlate of cerebral hemodynamics and oxygenation over a broad range of cerebral perfusion pressure and oxygenation. However, all three variables combined (i.e. optical patterns) strongly reflect the changes in cerebral hemodynamics and oxygenation accompanying those physiological conditions. These and similar patterns could potentially serve as a reference model for future studies in the human fetus where "gold standard" correlation methods do not exist.

Journal Article↗

Optical Brain Monitoring of the Cerebrovascular Effects Induced by Acute Cocaine Exposure in Neonatal Pigs.

> Objective: The purpose of this study was to assess the direct effects of cocaine on cerebral blood flow and oxygenation in newborn piglets using optical spectroscopy. Optical spectroscopy is capable of monitoring changes in cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin continuously, noninvasively, and in real time. Methods: Five anesthetized and ventilated newborn piglets were injected intravenously with 1 mg/kg cocaine through a central venous catheter over 60 seconds. Cerebral blood flow and oxygenation were assessed by optical spectroscopy and standard physiologic monitoring: mean arterial pressure, carotid blood flow, cerebrovascular resistance, and arterial hemoglobin oxygen saturation (by pulse oximetry). Results: Cocaine induced a profound increase in cerebrovascular resistance, a decrease in carotid blood flow, and a decrease in mean arterial pressure and heart rate. Cerebrovascular changes were detected readily by optical spectroscopy (i.e. a decrease in cerebral oxyhemoglobin was associated with an increase in deoxyhemoglobin). The hypotensive response augmented the cerebral vasoconstriction effect on carotid blood flow. A good correlation existed between the changes in carotid Doppler blood flow and total hemoglobin in each animal and for all animals combined. Peripheral arterial hemoglobin oxygen saturation measured by pulse oximetry remained normal throughout the experiment. Conclusions: The cause for the apparent idiosyncratic hypotensive response to intravenous injections of cocaine is uncertain and requires further investigation. Our study clearly demonstrates that optical spectroscopy might become an extremely useful tool for monitoring cerebral hemodynamics and oxygenation in cocaine-exposed fetuses and infants.

Journal Article↗

[Diagnosis of organ-confined prostate cancer by systematic biopsy under guidance of TRUS].

Systematic biopsy is useful to diagnose of prostate cancer. However, the usefulness of systematic biopsy for detection of organ-confined prostate cancer is unclear. There are three biopsy parameters, 1) percentage of biopsy cores involved with cancer (number of cores involves with cancer divided by total number of biopsy cores), 2) millimeters of cancer per biopsy core (total millimeters of cancer in the biopsy specimen divided by total number of biopsy cores) and 3) percentage of cancer in the biopsy specimen (total millimeters of cancer in the biopsy specimen divided by total millimeters of biopsy tissue). Although each biopsy parameter alone is not sufficient to detect organ-confined prostate cancer, the combination with these biopsy parameters and serum prostate-specific antigen levels improved the detection rates of organ-confined prostate cancer.

Biopsy↗

Detection of prostate carcinoma using prostate specific antigen, its density, and the density of the transition zone in Japanese men with intermediate serum prostate specific antigen concentrations.

BACKGROUND: This study was undertaken to determine whether the prostate specific antigen (PSA) density (PSAD) and PSAD of the transition zone (PSADT) are useful in the detection of prostate carcinoma in Japanese men with intermediate levels of serum PSA. METHODS: Two hundred and eighty-seven Japanese men with intermediate serum PSA levels (2.1 ng/mL to 10 ng/mL) underwent measurement of prostate volume by transrectal ultrasound (TRUS) and systematic biopsy under TRUS guidance. The volume of the transition zone was also measured by TRUS in 134 patients. The PSAD and PSADT were determined for each patient, and their relationship to prostate carcinoma detection was examined. RESULTS: Prostate carcinoma was detected in 30 of 287 patients (10.5%). Although the serum PSA levels were similar in patients with benign and malignant prostate disease (P = 0.541), the prostate volume (P 0.0009) and PSAD (P < 0.0001) differed significantly in the two groups; in the patients with prostate carcinoma, the prostate volume was smaller, and the PSAD higher, than in the patients with benign disease. At the PSAD cutoff value of 0.18 ng/mL/cm3 or greater, the sensitivity was 70% and the specificity was 67% for the diagnosis of prostate carcinoma. The PSAD was found to be significantly better in the differentiation between benign and malignant prostate disease than the serum PSA in the receiver operating characteristic analyses (P = 0.045). However, the receiver operating characteristic curve for PSAD was not significantly different compared with that for PSA in the men with negative digital rectal examination findings. Prostate carcinoma was detected in 9.0% (12 of 134) of the patients who underwent PSADT determination. Receiver operating characteristic analyses showed that PSADT was not superior to PSA in the detection of prostate carcinoma. CONCLUSIONS: In Japanese men with intermediate serum PSA concentrations, PSAD offers additional information useful in the detection of prostate carcinoma, but PSADT does not. Although use of PSAD may decrease the number of unnecessary biopsies, a significant number of prostate carcinomas may be overlooked. Therefore, the authors recommend that serum PSA levels continue to be used as an indicator for biopsy in Japanese men.

Adult↗

Inhibitory effect of ethanol on the 5-HT3 receptor-mediated tachycardia in isolated guinea-pig atrium.

The influence of ethanol on 5-hydroxytryptamine (5-HT)-induced tachycardia mediated by 5-HT3 receptor activation in the isolated guinea-pig atrium was studied. Ethanol at 200 mM significantly inhibited 5-HT - but not isoproterenol- or histamine-induced tachycardia in the isolated guinea-pig atrium. The same inhibitory effect was observed in response to 2-propanol and chloral hydrate application. Both 2-propanol at 100 mM and chloral hydrate at 1 mM exhibited inhibitory effects on 5-HT -induced tachycardia as potent as those of ethanol at 200 mM. These alcohols did not inhibit the tachycardia induced by isoproterenol or histamine. The inhibitory effects of the alcohols seemed to be specific for 5-HT and to increase according to their lipophilicity. Our results suggest that the inhibitory effects of ethanol on 5-HT3 receptor-mediated tachycardia are related to the direct effect of ethanol on 5-HT3 receptors in the atrium.

1-Propanol↗

The ratio of free to total serum prostate specific antigen and its use in differential diagnosis of prostate carcinoma in Japan.

BACKGROUND: To improve the clinical usefulness of prostate specific antigen (PSA), unique methods have been proposed. The percentage of free PSA in serum facilitates the distinction between benign histologic conditions and prostate carcinoma while retaining high sensitivity. METHODS: Using monoclonal antibodies, an AIA total PSA assay system was established that recognized PSA equally in free or complex form. The clinical usefulness of the ratio of two different molecular forms of PSA was investigated using 268 archival serum samples. RESULTS: Men with prostate carcinoma had significantly lower ratios of free to total PSA than those with benign prostatic hyperplasia (BPH) (P = 0.0001). At total PSA levels between 2.1 and 10 ng/mL, medians of total PSA were not significantly different between men with prostate carcinoma and men with BPH. Differences in median percentages of free PSA for these two groups were statistically significant (P = 0.0001). The ratio of free to total PSA was useful for identifying prostate carcinoma in palpably benign glands with total PSA of 2.1-10 ng/mL (P = 0.0001), whereas total PSA was not useful for such identification. When calculated for low total PSA levels between 2.1 and 4 ng/mL, sensitivity and specificity were 91.7% and 72.2%, respectively, with a cutoff value of 17%. This ratio of free to total PSA was as useful as PSA density in receiver-operating curve analysis. CONCLUSIONS: The use of the ratio of free to total PSA renders total PSA of greater use of distinguishing prostate carcinoma and is applicable to patients with low total PSA. Elderly men with a clinical diagnosis of BPH who are scheduled for surgery may benefit from the determination of this ratio.

Aged↗

Clinicopathologic study of angiogenesis in Japanese patients with breast cancer.

To evaluate the clinicopathologic significance of angiogenesis as a prognostic factor and the objective methods for evaluating angiogenesis, we immunohistochemically stained a representative section of breast tumors with factor VIII-related antigen staining. There were 109 patients with primary breast cancer from 1971 to 1979. The two methods of identifying angiogenesis were the average microvessel count per square millimeter (AMC) and the highest microvessel count per square millimeter (HMC). There was no relation between microvessel count (AMC or HMC) or age, menopausal status, clinical tumor size (T), histologic classification, nuclear grade, node status, histologic grade (HG), mitosis index, or lymphatic invasion (LI). There was a relation between microvessel count and blood vessel invasion (BVI) (HMC:p = 0.0007) and tumor necrosis (TN) (HMC:p = 0.0050). Univariate analysis showed that AMC or HMC was a statistically significant predictor of overall survival in all patients (p = 0.0086 and p = 0.0307, respectively). Multivariate analysis showed that AMC was an independent predictor of node status when we fitted a model with node status, BVI, and either AMC or HMC; but HMC was not independent. However, when we fitted a model including all 11 of the other indicators and AMC or HMC, the node status, HG, and LI were independent predictors, but AMC and HMC were not. Although AMC was a better method than HMC for evaluating angiogenesis, we cannot confirm angiogenesis as a significant independent prognostic factor associated with long-term survival in Japanese breast cancer patients.

Adult↗

An assessment of the usefulness of serum prostate-specific antigen level and cancer volume in biopsy specimens to predict the extent of prostate cancer.

OBJECTIVE: To evaluate the usefulness of the combination of serum prostate-specific antigen (PSA) and cancer volume in biopsy specimens as markers to predict the extent of prostate cancer. PATIENTS AND METHODS: Of patients presenting at our hospital with urinary symptoms suggesting prostatic disease, 311 (median age 70 years, range 42-88) with either nodules in the prostate detected by digital rectal examination or with elevated serum PSA levels (> 2.0 ng/mL) underwent systematic biopsy; 69 had prostate cancer. The cancer volume in the biopsy specimens was examined pathologically by measuring the percentage of the biopsy core involved with cancer, the length of cancer tissue per biopsy core and the percentage of cancer in the biopsy specimen. The relationship of serum PSA level, cancer volume in the biopsy specimen and the extent of disease was examined. RESULTS: The volume of cancer in the biopsy specimens increased with increasing serum PSA concentration and the incidence of skeletal metastasis. The number of patients with extraprostatic disease or bony metastasis was significantly higher for these Japanese patients with a serum PSA of < 10 ng/mL. All six patients with a positive bone scan and who had a serum PSA level of < 10 ng/mL had a larger volume of cancer in their biopsy specimens. Among patients who underwent radical prostatectomy and pelvic lymphadenectomy, the incidence of extraprostatic disease increased with the value of each biopsy variable. Among patients with similar serum PSA levels, those showing higher values for the biopsy variables also showed extraprostatic disease. Among those with extraprostatic disease, seminal vesicles were involved by cancer in four of six patients with > 40% positivity in the biopsy cores, > 1.5 mm of cancer per biopsy core or > 20% cancer in the biopsy specimens. Lymph node metastasis was found in four of five patients with serum PSA levels of > 20 ng/mL and a large cancer volume in the biopsy specimen. CONCLUSIONS: These results indicate that a combination of serum PSA level and cancer volume in the biopsy specimen could be useful markers for predicting the extent of prostate cancer.

Adult↗

"Collision phenomenon" of prostate and bladder cancers in lymph node metastases.

We report here the case of a 78-year-old man who, 15 months after orchiectomy for palliation of prostate adenocarcinoma, was diagnosed as having squamous cell carcinoma of the urinary bladder. The bladder cancer was treated surgically, including dissection of pelvic lymph nodes. Some of these nodes were observed at surgery to be swollen, and were found on pathologic examination to exhibit the collision phenomenon: the mixing and mingling of cancer cells representing 2 distinct topographic origins. This case suggests that the possibility of collision phenomenon should be considered whenever any metastasis (but especially one in the lymph nodes) is found in a patient diagnosed with 2 different types of cancer. Moreover, it reminds us that diagnosis of one type of cancer does not rule out the possibility of another.

Adenocarcinoma↗

Evaluation of the AMPLICOR CMV test for direct detection of cytomegalovirus in plasma specimens.

We evaluated the AMPLICOR CMV test (PCR) for the direct detection of cytomegalovirus in plasma. Sixty-eight specimens were involved for the comparison between the AMPLICOR test and the antigenemia assay. The sensitivities, specificities, and positive and negative predictive values were 97.1, 100, 100, and 97.1%, respectively, for the AMPLICOR test and 79.4, 100, 100, and 82.9%, respectively, for the antigenemia assay.

Antigens, Viral↗

[MPO-ANCA related vasculitis with pulmonary hemorrhage during propylthiouracil (PTU) therapy].

We described a case of pulmonary hemorrhage associated with myeloperoxidase-antineurophil cytoplasmic antibodies (MPO-ANCA) without renal involvement during propylthiouracil (PTU) treatment. A 36-years old female was admitted to our hospital because of progressive dyspnea with hemosputum after flu-like symptom and episcleritis. She had been receiving PTU for three years to Graves' disease. On admission her chest Xp showed bilateral massive infiltrative shadow and bronchofiberscopy demonstrated pulmonary hemorrhage. MPO-ANCA and anti-thyroperoxidase antibodies were positive, but she had normal urinalysis and normal renal function. After withdraw of PTU, pulmonary hemorrhage disappeared. But 15 days later pulmonary hemorrhage recurred associated with high MPO-ANCA titer. Corticosteroid bolus therapy and oral cyclophasphamide administration improved pulmonary hemorrhage, and MPO-ANCA titer also decreased. It is suggested that MPO-ANCA and PTU might be closely related to the pathogenesis of pulmonary hemorrhage in this case.

Adult↗

Elevation of serum levels of matrix metalloproteinase-2 and -3 as new predictors of recurrence in patients with urothelial carcinoma.

BACKGROUND: The relationship between serum levels of matrix metalloproteinase-2 (MMP-2) and MMP-3 and recurrence in patients with urothelial carcinoma after complete resection was studied to determine whether the enzymes could be a new predictor of recurrence. METHODS: Serum levels of MMP-2 and MMP-3 in 146 healthy controls, 52 patients with superficial (noninvasive) and 35 patients with advanced (invasive or metastatic) bladder carcinoma, and 30 patients with advanced upper urothelial carcinoma (renal pelvis and ureter) were measured by a one-step sandwich enzyme assay. RESULTS: Among the 53 patients with advanced urothelial carcinoma who underwent complete resection, the 1- and 3-year disease free survival rates of patients with elevated serum levels of either or both of the enzymes were 51% and 19%, respectively, whereas those of patients with normal serum levels of these enzymes were much higher, 86% and 79%, respectively (P < 0.005). In pT2N0M0 and pT3N0M0 patients who underwent complete resection, the recurrence rate in those with preoperative elevated serum levels of either or both of the enzymes was significantly higher than that in patients with normal levels (75% vs. 8%; P < 0.001). The 1- and 3-year disease free survival rates of pT2N0M0 and pT3N0M0 patients with elevated serum levels of either or both of the enzymes were 55% and 21%, respectively, which was significantly lower than that of patients with normal levels (92%; P < 0.001). CONCLUSIONS: The results of this study indicate that the elevation of serum levels of either MMP-2 or MMP-3 or both could be new predictors of recurrence in patients with advanced urothelial carcinoma after complete resection.

Adult↗

Cell kill kinetics of an antineoplastic nucleoside, 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine.

The cytotoxic properties of 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine (DMDC) were compared with those of 1-beta-D-arabinofuranosylcytosine (ara-C), using SK-MEL-28(P-36) human melanoma cells. DMDC and ara-C were most cytotoxic to cells in the S phase of the cell cycle. Cell cycle progression in S phase was blocked by both compounds. Treatment with DMDC (1 microgram/mL) or ara-C (1 and 30 micrograms/mL) did not increase cytotoxicity against asynchronous cells when the exposure time was prolonged from 1 to 6 hr, but did increase cytotoxicity thereafter. These findings suggest that cells in S phase are rapidly killed by the treatment but are temporarily prevented or delayed entry into the drug-sensitive S phase. On the other hand, DMDC treatment at a higher concentration (30 micrograms/mL) increased cytotoxicity in a time-dependent manner. Intracellular DMDC 5'-triphosphate (DMDCTP) increased in proportion to exogenous DMDC concentration, which was not saturated by treatment with a maximum concentration of the compound at 80 micrograms/mL. In contrast, intracellular ara-C 5'-triphosphate reached peak level when the cells were treated with ara-C at 8 micrograms/mL. The cytotoxicity of DMDC treatment for 4 hr increased relative to the intracellular DMDCTP accumulated during the period. These findings suggest that in cells treated with DMDC at a high concentration, an effective DMDCTP level is maintained for an extended period after washing out the compound from the medium. Consequently, the cells would be killed in the same way as in the case of extended exposures over 6 hr to DMDC at low concentration or to ara-C, in addition to acute S-phase-specific cytotoxicity.

Antineoplastic Agents↗

Prognostic significance of circulating matrix metalloproteinase-2 to tissue inhibitor of metalloproteinases-2 ratio in recurrence of urothelial cancer after complete resection.

The relationship between the serum matrix metalloproteinase-2 (MMP-2):tissue inhibitor of metalloproteinases-2 (TIMP-2) ratio and disease recurrence was examined in 53 urothelial cancer patients with muscular invasion or with lymph node metastasis who underwent complete resection. The mean MMP-2:TIMP-2 ratio in 31 patients with recurrence was significantly higher than that in 22 patients without recurrence (P < 0.05). Disease-free survival of patients with high MMP-2:TIMP-2 ratios was extremely poor compared with that of patients with lower ratios (P < 0.01). Cox's multivariate analysis suggests that the serum MMP-2:TIMP-2 ratio would be a new independent prognostic indicator of urothelial cancer recurrence.

Female↗