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Biomedical subjects

Y Ohsaki

Publications and source records attributed to Y Ohsaki.

At least 73 records · Page 4Linked to original sources

[Randomized trial of cisplatin plus ifosfamide versus cisplatin plus vindesine for non-small cell lung cancer (NSCLC)].

Between 2/87 and 10/89, 83 patients (pts) with previously untreated NSCLC were assigned at random to receive either the PI regimen (cisplatin 80 mg/m2 dl and ifosfamide 2 g/m2 d 1, 2, 3, q 3-4 wks) or the PV regimen (cisplatin 80 mg/m2 d 1 and vindesine 3 mg/m2 d 1, 8, 15, q 3-4 wks). Three pts (2 PI regimen, 1 PV regimen) were ineligible for the study and 13 pts (7 PI regimen, 6 PV regimen) did not complete it. Thirty-three PI regimen pts and 34 PV regimen pts completed 2 or more cycles of the treatment and were evaluated. Patient characteristics were almost identical in both groups in terms of sex, age, pathological types, stage, performance status and number of chemotherapy cycles. For the PI regimen, there were 1 C.R. and 6 P.R., and the response rate was 21.2% (7/33). In the PV regimen, there were 11 P.R., and the response rate was 32.4% (11/34). The median survival time (MST) for PI regimen was 29 weeks (range 12-156 wks) and for PV regimen 40 weeks (range 8-138 wks). The difference in the survival curves for the 2 regimens was not statistically significant. Toxicities for the 2 regimens were similar except for greater leukopenia and one treatment-related death due to renal toxicity on PI regimen. These results suggest that PI regimen is not superior to PV regimen in the treatment of NSCLC.

Aged↗

Immunohistochemical demonstration of amelogenin penetration toward the dental pulp in the early stages of ameloblast development in rat molar tooth germs.

In order to examine the synthesis and secretion of enamel protein by ameloblasts in their early stages of development, immunohistochemical localization was carried out at light and electron microscopic levels using a monoclonal antibody produced in a preliminary experiment. Materials used were tooth germs of mandibular first molars of rats at 0-5 days after birth. Immunoblot analysis after two-dimensional electrophoresis revealed that antigen molecules recognized by the monoclonal antibody were amelogenins of 26-28 kDa (pI, 6.6-7.0). An immunohistochemical examination using this monoclonal antibody demonstrated that the presecretory ameloblasts in their early stages of differentiation both synthesized amelogenin and secreted through a classical merocrine secretory pathway. In some presecretory ameloblasts as well as ameloblasts we observed the distended cisternae of rough endoplasmic reticulum (rER) which demonstrated heterogenous immunolabelling. The immunolabellings were also detected in the predentin as well as the intercellular spaces of odontoblasts and dental pulp cells which indicated penetration of amelogenin from the presecretory ameloblast layer to the dental pulp. The presence of coated pits at the plasma membrane of odontoblasts in close proximity to enamel protein along with the immunolabelling of lysosomes of the odontoblasts suggests the phagocytosis of the enamel protein into the odontoblasts. These observations suggest the possibility that the penetration of enamel protein toward the dental pulp and odontoblasts plays a role in the interaction between ameloblasts and odontoblasts.

Ameloblasts↗

Distribution of type I and type III collagen in the developing periodontal ligament of mice.

In order to localize type I and type III collagen in developing periodontal ligament, immunofluorescent and immunoelectron microscopic examinations were undertaken. The materials used were the maxillary molars of CF1 mice, 13 days to 6 months old. The antibodies used were monospecific polyclonal antibodies against type I or type III collagen raised in rabbits or guinea pigs, respectively. Single- and double-staining methods were employed in immunofluorescent as well as immunoelectron microscopic examinations. In immunofluorescent examinations, during the development of the periodontal ligament, periodontal fibers showed intense and homogenous staining for both type I and type III collagen; while Sharpey's fibers in the alveolar bone showed a heterogenous staining in cross and longitudinal sections for both types of collagen. In immunoelectron microscopic examinations, fibrils of periodontal fibers showed positive staining for type I and type III collagen simultaneously and had characteristic cross-banding and had a large diameter (ranging 40 approximately 80 nm) which remained constant during development. Sharpey's fibers in the alveolar bone or in the cementum showed the same staining pattern as the periodontal fibers, except for an afibrillar area which showed negative staining for both type I and type III collagen. The results obtained suggest that periodontal fibers and Sharpey's fibers consist of cofibrils of at least type I and type III collagen.

Aging↗

Immunohistochemical study of the relationship between extracellular matrix and root bifurcation in the mouse molar.

In order to investigate epithelial-mesenchymal interaction during root bifurcation, the distribution of type III and I collagen, fibronectin and laminin in the epithelial-mesenchymal junction between the dental epithelia (epithelial diaphragm and interradicular process) and the cells of the dental papilla (or pre-odontoblasts) was examined, using maxillary first molar tooth germs of CF1 mice from day 1-16 after birth. Three-dimensional reconstructions of the immunofluorescent patterns were made from serial sections of tooth germs from day 3-9, stained with the antibodies against the collagens. The findings were as follows. (1) Type III collagen was first seen in the epithelial-mesenchymal junction at the tip of the interradicular process, where it sprouted from the epithelial diaphragm, and spread along the interradicular process toward its base, accompanied its extension, and then disappeared on completion of root bifurcation. No staining was seen in the epithelial-mesenchymal junction at the epithelial diaphragm during and after root bifurcation. (2) Type I collagen appeared in the epithelial-mesenchymal junction at the base of the interradicular process, where it sprouted from the epithelial diaphragm and spread toward the tip of the interradicular process, following its extension, and increased on completion of the root bifurcation. No staining was seen in the epithelial-mesenchymal junction at the epithelial diaphragm during or after root bifurcation. (3) Fibronectin and laminin remained constant in the epithelial-mesenchymal junction, both at the interradicular process and the epithelial diaphragm, during and after root bifurcation. These findings suggest that type III collagen may play a significant role in the early stage of root bifurcation in the molar.

Animals↗

Proximal gastric vagotomy with carbon dioxide laser: experimental studies in animals.

Proximal gastric vagotomy has been widely used as a surgical treatment for peptic ulcer disease. However, it is technically complex and time-consuming. Moreover, it may cause circulatory problems in the gastric mucosa. We have reported a new method of blood flow-preserving vagotomy with a carbon dioxide laser (CO2 laser vagotomy) developed in our laboratory. To assess its efficacy, we used cysteamine-induced ulcer and measured gastric mucosal blood flow in rats. The incidence of cysteamine-induced ulcer formation was reduced significantly in the group that underwent CO2 laser vagotomy compared with a group treated with proximal gastric vagotomy. Gastric mucosal blood flow was significantly better in the CO2 laser vagotomy group. Long-term follow-up of acid reduction was evaluated in dogs by the pentagastrin-stimulation test. Acid reduction in dogs was satisfactory during the 12 months of this study. CO2 laser vagotomy is a new, easy, time-saving, and circulatory-preserving technique for peptic ulcer disease.

Animals↗

[Effects of chronic volume loading on atrial natriuretic peptide release in human].

In the present study, we investigated whether release of hANP increases during mild and long-term volume loading. Eight lung cancer patients in good performance state (five men and three women, 35 to 68 years), who needed to have pre-hydration for cancer chemotherapy with cisplatin, were infused with about seven liters of isotonic saline over 48 hours through Swan-Ganz catheter placed in the pulmonary artery. The mean infusion rate was 0.042 ml/min.kg body weight. During the infusion, change in plasma volume (delta PV) increased by 5.8 + 3.3 (mean +/- SE) %. Right atrial pressure (RAP) did not change significantly, and pulmonary artery wedge pressure (PAWP) increased from 4.3 +/- 1.0 to 5.8 +/- 0.7 mmHg. Plasma hANP was significantly elevated from 50.6 +/- 0.7 to 105.1 +/- 19.3 pg/ml by the second day of the infusion with a suppression of plasma renin activity (PRA) and aldosterone, though plasma ADH did not change. The infusion rate at 20:00 on the first day was the same as that on the second day. Further increase in plasma hANP was shown at 20:00 on the second day compared with the level at the same time on the first day, though RAP, PAWP and delta PV did not change. These results indicate that mild and chronic volume loading increases plasma hANP, and suggest that the prolongation of volume expansion plays an important role in the releasing of hANP in humans.

Adult↗

[A case of spontaneous regression of malignant lymphoma, complicated with miliary tuberculosis, liver dysfunction and pancytopenia].

An 82-year-old woman was admitted to Iwamizawa Rosai Hospital, Cardiovascular Medicine, for detailed examination of an aneurysm of abdominal aorta. CT scan revealed marked swelling of para-aortic lymph nodes which regressed spontaneously in three months. She was re-admitted to our hospital because of general malaise and gait disturbance. Her chest X-ray on the second admission revealed miliary disseminated shadows, which were confirmed to be tuberculous granuloma by lung biopsy. She was initially well controlled with anti-tuberculosis drugs, followed by severe liver dysfunction and pancytopenia, and died of respiratory and cardiac failure. At autopsy, wide-spread malignant lymphoma and miliary tuberculosis of the lung were found. The cause of liver dysfunction was strongly suspected to be due to infiltration of the lymphoma cells to portal triads of the liver. Hemophagocytosis found in the bone marrow, spleen and liver might be consistent with clinically so-called "hemophagocytic syndrome", causing pancytopenia, associated with infection.

Aged↗

[Combination effect of caffeine and cisplatin on a cisplatin resistant human lung cancer cell line].

The development of resistance to anti-cancer drugs is a major factor in limiting the response rate of cancer chemotherapy. Several mechanisms of such resistance are reported. Recently, expression of MDR gene and synthesis of p-glycoprotein by the MDR gene was reported as a mode of multi-drug resistance, but the mechanism of the resistance to cisplatinum (CDDP) remains unclear. Detoxification of CDDP, increase of the efflux of the drug and increase of DNA repair are considered to be the mode of CDDP resistance. It is widely documented that caffeine enhances the cytocidal effect of certain anti-cancer agents. The inhibition of DNA repair by caffeine has been considered to be one mechanism which enhances the cytocidal effect of such agents. We conducted the present study to evaluate the combination effect of caffeine and CDDP on the human lung adenocarcinoma cell line PC9/P and its CDDP resistant cell line PC9/R. Cell growth inhibition was measured by clonogenic assay and cell cycle analysis was performed with propidium iodide (PI) stain using flow cytometer (FCM). Caffeine enhanced the effect of CDDP on PC9/P synergistically. However, the combination effect of the two drugs was not apparent on PC9/R. Caffeine decreased G2M accumulation due to CDDP exposure in both cell lines. The data indicate that caffeine does not overcome the resistance of PC9/R, whereas caffeine enters PC9/R. It is suggested that increase of DNA repair might not be a mode of the CDDP resistance of PC9/R.

Adenocarcinoma↗

The effects of photosensitization by hematoporphyrin derivative on the protein content of cultured human lung cancer cells. A flow cytometric analysis.

In order to study the cytotoxic mechanisms of photodynamic therapy (PDT), the changes in the intracellular content of protein and DNA of cultured human lung cancer cells were examined by flow cytometry using the fluorescent dyes fluorescein isothiocyanate (FITC) and propidium iodide (PI). Immediately after PDT, the protein content increased while the DNA content showed little change. After more than 24 hours, the protein and DNA content were markedly decreased in lethally damaged cells; in sublethally damaged cells, however, the protein content gradually decreased to the level of that before PDT while the DNA content showed little change. These changes in the protein content may reflect the impairment of the plasma membrane function by PDT and its subsequent recovery in some cells.

DNA, Neoplasm↗

[Scanning electron microscopic observation of mouse ascitic carcinoma cells after intraperitoneal chemotherapy with cisplatinum].

The peritoneal surface of the lesion was observed after treatment by scanning electron microscopy (SEM) to evaluate the anticancer effect of Cisplatinum (CDDP). CDDP (0.1 mg/day bolus) was injected intraperitoneally to the DDN mice in which 3 X 10(7) MM2 tumor cells were inoculated the day before treatment. The anticancer effect was examined from 2nd to 7th consecutive day after tumor cells implantation, and the following results were obtained. 1) MM2 tumor cells were covered by powder-like material consisted with CDDP and were destroyed. 2) Mesothelial cells were also degenerated by powder-like material of CDDP. 3) In CDDP group, only a little intraperitoneal effusion and adhesion were observed. 4) These results suggested that CDDP exerted anti-tumor cell effects on peritonitis carcinomatosa.

Animals↗

Flow cytometric analysis of the kinetic effects of cisplatin on lung cancer cells.

The effects of cisplatin on the cell cycle and DNA synthesis of human lung adenocarcinoma cell line PC-9 were examined by flow cytometry. The cellular DNA content and the bromodeoxyuridine (BrdUrd) incorporation rate were measured simultaneously using a monoclonal anti-BrdUrd antibody. Following exposure to cisplatin (1.0 micrograms/ml) for 1 and 24 hr, the bivariate DNA/BrdUrd distributions revealed a delayed S-phase transit and an accumulation of cells in the G2M phase. The BrdUrd-linked green fluorescence intensity continued to decrease with the lapse of time. However, early- and mid-S-phase cells soon recovered DNA synthesis activity, and the former showed higher activity than the control cells. These findings suggested the vigorous DNA synthesis of cells in early S phase. However, for quantitative analysis of chemotherapeutic effects, some problems remained to be resolved regarding the condition for DNA denaturation and its alteration by the agents.

Adenocarcinoma↗

The relation between phenytoin-receptor and glucocorticoid in the induction of cleft palate with phenytoin in mice.

Both phenytoin (PHT) and glucocorticoid (GC) have been reported to be an effective teratogen for the production of cleft palate. The authors suggest the possibility that a part of GC-receptor to which PHT competitively bind (common receptor with PHT), participate in the production of cleft palate. In the present study, as one of the studies for the elucidation of the mechanism of cleft palate induction with PHT, we investigated the PHT-receptors and its relation with GC in the lung tissue of mice, which were either sensitive (CF1) or resistant (C57BL/6) to PHT or GC. Scatchard analysis of the specific binding of 14C-PHT to the cytosol protein revealed that the total capacity of PHT-receptor for CF1 (1,571 fmole/mg protein) was much greater than that for C57BL/6 (994 fmole/mg). The value of the Kd's for these strains, however, were 18.1 and 16.5 nM, respectively, indicating the absence of any great difference between both strains. The capacity of the common receptors with GC for CF1 (236 fmole/mg) was greater than that for C57BL/6 (126 fmole/mg). But, the value of the Kd's for these strains were 5.4 and 3.1 nM, respectively, indicating the absence of a great difference between the strains. The analysis indicated that the lung tissue cytosols of both strains also contain the proper receptor for PHT, which is in a much greater amount than that of the common receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

[Two cases of miliary tuberculosis with SIADH].

Two cases of miliary tuberculosis with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) were reported. Case 1. A 70-year-old woman suffering from general fatigue and appetite loss developed neck stiffness and stupor three days after admission. The chest X-ray film showed a miliary pattern in both lungs. The lumber puncture showed high pressure and increased leucocytes in the cerebrospinal fluid. Serum natrium concentration was 113 mEq/L. Tubercle bacilli were seen in the broncho-alveolar lavage fluid by the Ziehl-Nielsen staining. An improvement in electrolytes balance was produced by 2.5% NaCl and antituberculous treatment, then her mental function recovered. Case 2. A 71-year-old man was admitted with gastric ulcer. When he developed dry cough thirty days after admission, the chest X-ray film showed a miliary pattern in both lungs. Acute respiratory failure advanced concomitantly. Tubercle bacilli were seen in the sputum (Gaffky 5) by the Ziehl-Nielsen staining. Antituberculous treatment was started. Although the miliary shadow improved gradually, hyponatremia was rather progressing. The following values for serum constituents were determined: sodium, 118 mEq/L; antidiuretic hormone, 10.3 pg/ml. Antituberculous treatment and supplement of NaCl (10 g/day) improved serum natrium level. He had no mental disturbance in his clinical course. In both cases, thyroid, renal and adrenal function were normal. Systemic edema and dehydration did not exist at the state of hyponatremia, and it was very clear that laboratory data were compatible with SIADH criteria. Miliary tuberculosis is one of the least commonly recognized causes of SIADH.

Aged↗