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Biomedical subjects

M Ono

Publications and source records attributed to M Ono.

1,114 records · Page 62Linked to original sources

Pharmacokinetics, N1-glucuronidation, and N4-acetylation of sulfa-6-monomethoxine in humans.

Sulfamonomethoxine (S) is metabolized by O-dealkylation, N4-acetylation, and N1-glucuronidation. In humans, only N1-glucuronidation (12%) and N4-acetylation (36%) takes place. The N1-glucuronide is directly measured by HPLC. When N4-acetylsulfamonomethoxine (N4) is administered as the parent drug, N1-glucuronidation does not occur. After an oral dose, fast and slow acetylators show a similar t1/2 for S (25.0 +/- 4.6 hr vs. 29.8 +/- 4.8 hr; p = 0.459), and the t1/2 of the N4-acetyl conjugate is also similar in fast and slow acetylators (25.0 +/- 4.64 hr vs. 29.8 +/- 4.8 hr, p = 0.459). The intrinsic mean residence time of N4 is 7.1 +/- 2.3 hr. The mean total body clearance of S is 5.0 +/- 1.3 ml/min, the renal clearance is 0.84 +/- 0.26 ml/min, and the volume of distribution at steady state is 11.7 +/- 3.4 liters. The renal clearance of N4 is 17.89 +/- 4.19 ml/min. No measurable concentrations of the N1-glucuronide of S are found in plasma. The protein binding of S is 92%. N1-glucuronidation results in an 80% reduction in the protein binding of S (11%). N4 shows a high protein binding of 98%. Approximately 60% of the oral dose of S is excreted in the urine.

Acetylation↗

Isolation of serotype 2 Marek's disease virus from birds belonging to genus Gallus in Japan.

Serotype 2 of Marek's disease virus (MDV) was isolated from apparently healthy birds belonging to genus Gallus that had no history of vaccination with MDV or herpesvirus of turkeys (HVT). Buffy-coat cells from these birds were inoculated onto chicken embryo fibroblast (CEF) cultures for primary isolation. Thirteen isolates from one golden pheasant and three white silky fowls, three black silky fowls, three Japanese long crowers, and three Japanese bantams produced herpes-like cytopathic effects (CPE) in the CEF cultures. Using serotype-specific monoclonal antibodies to MDV and HVT, 11 isolates were identified as serotype 2 MDV by indirect fluorescent antibody tests. The other two isolates were complicated with serotypes 1 and 3 of MDV-related viruses. Of 13 isolates, three cloned by the limiting-dilution method were further characterized as serotype 2 MDV biologically, genetically, and serologically. The results showed that the birds of the genus Gallus were naturally infected with serotype 2 MDV. This is the first report ever published about the distribution of serotype 2 MDV among healthy birds of the genus Gallus.

Animals↗

Clinical value of deconvolution analysis in radionuclide renal study.

Deconvolution analysis was applied to radionuclide renal study. The purpose of this study was to clarify the underlying renal physiology that determines the shape and values of the transfer function. Analysis of the renal models revealed that the initial height of the transfer function is the ratio of the radioactivity extracted by the kidney to that in the input function. In addition, the shape of the transfer function displayed the distribution of the transit times and enabled us to evaluate the percentage of nephrons having a particular transit time. Based on the relation between the input and output function, a new method for measuring GFR or ERPF was developed in which the input function was corrected by the plasma radioactivity at 5 min after injection of the tracer. As one of the advantages of the transfer function, it was proved clinically that the contribution of the blood background is automatically eliminated from the amplitude of the transfer function. From these findings, our method for the measurement of GFR was considered superior to that proposed by Gates and highly useful for routine radionuclide renal study.

Glomerular Filtration Rate↗

Cervicovaginal and endometrial cytology in ovarian cancer.

The clinical significance of cytologic examination was studied in 114 patients with ovarian cancer who had received preoperative cytologic examinations. The overall positive rate of the cytologic examinations was 26.3% (30 of 114): 22 (19.3%) of the 114 cases had positive cervicovaginal smears while 13 of 31 endometrial aspiration smears (41.9%) were positive. The positive rate was not related to the volume of ascites but rather to its presence or absence. Thus, if ascites was observed, the positive rate was about 2.1 times higher than if it was absent. In two of four cases of ovarian cancer with no endometrial invasion but a positive cytologic examination of ascitic fluid, fallopian tube specimens contained cancer cells; this suggests that ovarian cancer cells may reach the cervix and/or vagina by passing through the fallopian tube, particularly if ascites is present. Since cytologic examination, especially of endometrial aspiration smears, shows a high positive rate if ovarian cancer cells are observed in the abdominal cavity, cytology should be used as an important ancillary method for the assessment of ovarian cancer.

Adenocarcinoma↗

CT retrograde pancreatography using an indwelling balloon catheter.

We report a new technique for computed tomography (CT) of the pancreas during retrograde injection of contrast material into the pancreatic duct via an in situ balloon catheter placed by duodenoscopy (CT-RP). The method resulted in more stable ductgrams at CT than were obtained with other methods. Our data suggest that CT-RP provides useful information in evaluating pancreatic lesions that produce subtle or insignificant abnormalities of the outline of the pancreas and the ductal system on conventional CT and ERP.

Catheterization↗

Electron capture detection-gas chromatographic determination of diaminotoluenes in polyurethane foam as heptafluorobutyryl derivatives.

A simple gas chromatographic (GC) method has been developed to determine 2,4- and 2,6-diaminotoluenes in polyurethane foam. Diaminotoluenes were reacted with heptafluorobutyric anhydride in toluene, and the products, bis-heptafluorobutyrates, were determined by GC, using a 3% silicone OV-330 column. The 2,4- and 2,6-diaminotoluenes can be detected as heptafluorobutyryl derivatives by using an electron capture detector at levels of 5 and 2 pg, respectively. Finally, 2.7-3.0 micrograms/g of 2,4- and 1.3-1.9 micrograms/g of 2,6-diaminotoluene were detected in 3 commercial polyurethane foams.

Chromatography, Gas↗

Computed tomographic evaluation of adrenal glands in patients with bronchogenic carcinoma.

One hundred thirty-four patients with histo-pathologically proven bronchogenic carcinoma underwent computed tomography (CT) of the thorax and adrenal glands. Prospectively, 23 of the 134 patients had adrenal metastasis, based on CT criteria for enlargement of the gland. Retrospectively, however, some proved to be false positives. In addition, the diagnosis of adrenal metastasis frequently altered the initial staging and the treatment modality. We suggest that valid diagnoses of adrenal metastases on CT scan be made on the basis of altered shape as well as on altered size of the gland.

Adenocarcinoma↗

In vivo augmentation of the intratumoral concentration of 5-fluorouracil by cepharanthine--a biscoclaurine alkaloid.

We have investigated the interaction between Cepharanthine (CEP), a multi-functional alkaloid that has the capacity to stabilize the cell membrane, and 5-fluorouracil (5-FU) against a human colon cancer cell line (RPMI 4788) transplanted into nude mice. Their anti-tumor effects were assessed in a group of 7 mice intravenously injected with CEP (5 mg/kg/day) and/or 5-FU (15 mg/kg/day) during a 3-week treatment. The results were compared with a control and a 5-FU group, which received saline solution and 5-FU alone, respectively. The tumors were harvested 2 h after 5-FU administration. On an additional 4 groups of 5 mice, the intratumoral concentration of 5-FU was assessed by a high performance liquid chromatographic (HPLC) method 2, 4, 6 and 12 h following CEP (5 mg/kg) injection 1 h prior to, simultaneously, and 1 h after injection of 5-FU (30 mg/kg). The mean (SD) intratumoral concentration of 5-FU was 0.16 (0.05) mu g/g, 0.32 (0.19) mu g/g, 0.32 (0.16) mu g/g and 0.21 (0.13) mu g/g in the control and the three other groups treated with CEP, respectively. This concentration was about twice as high in mice simultaneously treated with CEP compared to those treated by 5-FU alone. Relatively higher concentrations of 5-FU were noted up to 4 h following 5-FU injection in mice treated with CEP than in those injected only with 5-FU. CEP also enhanced the inhibitory effects of the 5-FU on tumor growth rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

Cerebellar arteries originating from the internal carotid artery.

PURPOSE: To study the incidence of cerebellar arteries originating directly from the internal carotid artery, and to discuss the probable embryological origin and clinical implications of this anatomical anomaly. METHODS: We reviewed 5500 angiographic studies done at our institution in the last 4 years, searching for these anomalous vessels as well as for other anatomical variants. RESULTS: Eleven cerebellar arteries originating directly from the internal carotid artery and nine embryonic cerebral arteries were found. CONCLUSION: These arteries are considered persistent trigeminal artery variants and seem to occur as the result of the persistence of a primitive trigeminal artery associated with an incomplete fusion of the longitudinal neural arteries. These anomalous vessels are clinically significant particularly because of their role in endovascular therapeutic and surgical complications and the paradoxical lesions in the cerebellum that occur as a result of carotid disease.

Arteries↗

Comparative study of the effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on generation and mobilization of neutrophils in cyclophosphamide-treated neutropenic mice.

To examine the differential in vivo effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the recovery from neutropenia caused by chemotherapy, we directly compared the actions of these CSFs on neutrophil count in the bone marrow, spleen, and peripheral blood of mice treated with an anticancer drug, cyclophosphamide (CPA). Both G-CSF and GM-CSF stimulated the generation of neutrophils in bone marrow, but GM-CSF is only about 1/20 as effective as G-CSF. Both CSFs also stimulated the release of the generated neutrophils therefrom. G-CSF mobilized the neutrophils into both the circulation pool and the marginal pool, and these neutrophils were able to migrate into the inflammatory site when stimulated by casein. On the other hand, GM-CSF mobilize the neutrophils into the marginal pool but not the circulation pool, and they were not able to migrate into the inflammatory site. These findings indicate that G-CSF physiologically plays an important role as a factor which stimulates neutrophil mobilization from bone marrow into circulation as well as neutrophil generation in the bone marrow.

Animals↗

Granulocyte colony-stimulating factor shortens the optimal interval of repetition of chemotherapy with cyclophosphamide in mice.

To examine the effect of human granulocyte colony-stimulating factor (G-CSF) on the hemopoietic response to repeated treatment with the anticancer drug cyclophosphamide (CPA) in mice, we determined the optimal time interval between CPA doses which was required to equalize the recovery of neutrophils in the first and second cycle. G-CSF-treatment significantly shortened the optimal time interval of CPA doses when compared with treatment with the control vehicle. The studies on resistance to a second CPA cycle and hemopoietic parameters indicated that the resistance correlated positively with the granulocyte colony-forming cel (G-CFC) population in marrow, in both control and G-CSF-treated mice. In G-CSF-treated mice, moreover, the resistance correlated positively with the ratio of G-CFC in proliferative state and negatively correlated with the neutrophil levels in peripheral blood. These results suggest that G-CSF shortens the optimal time interval between CPA doses not only by accelerating the recovery of G-CFC but also by affecting the hemopoietic environment.

Animals↗

MR imaging of focal nodular hyperplasia of the liver: value of contrast-enhanced dynamic study.

To clarify the role of MR imaging of hepatic focal nodular hyperplasia (FNH), MR images of 11 patients with 13 FNH were retrospectively reviewed. MR imaging with T1- and T2-weighted spin echo sequences was performed for all lesions. Dynamic studies using the SPGR technique followed by postcontrast delayed T1-weighted images were performed in four patients with five lesions. Gd-DTPA enhanced T1-weighted images were obtained in five patients with six lesions. Two patients with single lesions received no contrast agent. The signal intensity, morphologic appearance, and enhancement patterns were evaluated. Dynamic MR study revealed homogeneous early vigorous enhancement and prolonged enhancement in all five lesions. On T1-weighted images, three lesions were hypointense, six were isointense, and four were hyperintense to the surrounding hepatic parenchyma. On T2-weighted images, four lesions were isointense and nine were hyperintense. A central scar was identified in eight lesions and showed delayed enhancement. It is concluded that dynamic MR studies are mandatory for diagnosing FNH.

Adolescent↗

Lung cancer associated with punctate calcification: CT and histological correlation.

The etiology of punctate calcifications in lung cancer was evaluated on the basis of CT and histological correlations. Seven cases of lung cancer with punctate calcifications were demonstrated on CT. The patients had undergone surgical resection (five men and two women, 60-70 years old; six adenocarcinomas and one squamous cell carcinoma), and each case was evaluated for its CT appearance and histological findings. The number of calcifications observed on CT varied from one to six. Most were eccentric, but some calcifications in four cases were within the more central portion of the nodules. Overall, in six of seven cases the calcifications were histologically estimated to be due to preexisting old granulomatous fibrotic changes or fragments of bronchial cartilage incorporated within the growing tumors. In only one case were the calcifications psammoma bodies within the tumor. We conclude that punctate calcifications in lung cancers correspond mostly to preexisting calcified granuloma or degenerated bronchial cartilage.

Adenocarcinoma↗

Positive interaction of bisbenzylisoquinoline alkaloid, cepharanthin, with vinca alkaloid agents against human tumors.

Cepharanthin (CE), a bisbenzylisoquinoline alkaloid drug, was tested in vitro and in vivo with chemotherapeutic agents, vincristine (VCR), vinblastine (VLB), and vindesine (VDS). The activity of these agents alone or in combination was tested against a human colon cancer cell line (RPMI 4788) or a human uterine cervical cancer cell line (HeLa), using a modified microcytotoxicity-viable cell staining assay. In the in vitro study, the antiproliferative activities of each vinca alkaloid were enhanced additively or synergistically by combination with CE in RPMI 4788 cells as well as HeLa cells. The sequential exposure of the RPMI 4788 cells or HeLa cells to both CE and each vinca alkaloid agent showed evidence of a more significant potentiation. The antiproliferative activity of the combination of each vinca alkaloid agent(VCR, VLB, or VDS) with CE was almost equivalent to the effect of each vinca alkaloid agent alone which was potentiated by CE tenfold through several hundredfold. In an experimental model of tumor growth and survival, in which RPMI 4788 cells were transplanted subcutaneously or intraperitoneally into BALB/c nu/nu mice respectively, CE (1 mg/kg) alone exerted not significant inhibitory activity against tumor growth or survival, and VCR (0.25 mg/kg) alone partially inhibited these antitumor activities. Furthermore, the antitumor effects of VCR were elevated synergistically by the simultaneous administration of CE. These studies indicate that due to their therapeutic potential, combinations of vinca alkaloid agent with CE might be a promising therapy for some human cancers.

Alkaloids↗