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Biomedical subjects

F Kobayashi

Publications and source records attributed to F Kobayashi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Rectal absorption of ozagrel from a suppository containing its commercial tablet in healthy human subjects.

A suppository containing an ozagrel tablet was prepared using Witepsol H-15 as a base, and its rectal absorption was studied in male human volunteers. In comparison, a commercially available ozagrel tablet was administered orally to all the individuals in a cross-over design. After rectal dosing, ozagrel was absorbed rapidly at a Tmax of 0.75 h, and its elimination half-life was longer than after oral dosing. The extent of absorption of ozagrel after both administration routes was similar. However, the bioavailability of the rectal suppository is 92 +/- 37% (mean +/- S.D.; n = 6) relative to the oral tablet. The tablet-containing suppository is easy to prepare, with its content being accurate and reproducible. Thus, the present study suggests that the rectal administration of an ozagrel suppository is a practical and promising alternative to oral administration, especially for patients who cannot take tablets orally. This study demonstrated for the first time the possibility of an ozagrel suppository in human subjects.

Adult↗
PubMed1996

Rapid growth of an ovarian clear cell carcinoma expressing LH/hCG receptor arising from endometriosis during early pregnancy.

The complete clinical course of a case of ovarian clear cell carcinoma expressing luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor arising from endometriosis in a pregnant woman is presented. A 31-year-old woman visited a private clinic in May 1993 for screening tests for infertility. Transvaginal ultrasonography revealed no abnormal findings in the uterus or ovaries. Her menstrual cycle was regular; however, a slight luteal insufficiency was noted. She had been treated with clomiphene, and soon became pregnant. She was diagnosed to be at 5 weeks gestation in June, and at the same time, an ovarian tumor with the diameter of 5 cm was identified. Since the tumor had grown rapidly and was 9 cm in diameter 1 week later, she was referred to our hospital. When she was admitted to our hospital at 9 weeks gestation, the tumor diameter was 14 cm and we found the solid portion within the ovarian tumor. The levels of the tumor markers CA125 and CA19-9 were 106 and 51 U/ml, respectively. The crown-rump length of the fetus (24 mm) was compatible with the gestational age, and fetal heartbeat was confirmed. Under the diagnosis of ovarian carcinoma, right salpingo-oophorectomy was performed at 10 weeks of gestation. Postoperative histological examination revealed a clear cell carcinoma and endometriosis of the right ovary. Immunohistochemically, the clear cell carcinoma stained positively for LH/hCG receptors and estrogen receptors, but not progesterone receptor. No malignant cells were detected by ascitic cytology. Exploratory specimens obtained at the time of operation from the left ovary and pelvic lymph nodes exhibited no malignant cells. Based on these findings, the pregnancy was allowed to proceed, and she delivered a 3010-g male baby at 39 weeks of gestation. She had no signs of recurrence for 2 years after the operation.

Adenocarcinoma, Clear Cell↗
PubMed1996

Production of interleukin 10 during malaria caused by lethal and nonlethal variants of Plasmodium yoelii yoelii.

We investigated the induction of T-helper cell subsets during the course of lethal or nonlethal bloodstage Plasmodium yoelii 17X infection in C57BL/6 mice, which are relatively susceptible to these intraerythrocytic parasites. C57BL/6 mice infected with the nonlethal variant (PyNL) showed a moderate level of parasitemia and resolution of primary acute infection by week 4. Mice infected with the lethal variant (PyL) developed fulminating parasitemia and ultimately died. T-helper subset function was assessed during infection by determining the kinetics of in vitro production of the Th1-derived cytokine interferon-gamma (IFN-gamma) and the Th2-derived cytokine interleukin 10 (IL-10) by means of bioassay and enzyme-linked immunosorbent assay (ELISA), respectively. Spleen cells obtained from mice infected with PyL within the 1st week of infection produced high levels of IL-10 and IFN-gamma in response to malaria antigen. IL-10 also appeared in sera from PyL-infected mice at the same time at which the in vitro IL-10 response peaked. In contrast, spleen cells from mice infected with PyNL failed to produce IL-10 during the course of infection. CD4+ T-lymphocytes from mice infected with the lethal variant were a major source of IL-10, although non T-cells were also involved in the production of IL-10 during this malaria infection. In addition, the initial burst of IL-10 in response to malaria antigens was seen concomitantly with the production of IFN-gamma within the 1st week of infection. These results indicate that both Th1 and Th2 subsets of T-helper lymphocytes are activated during infection with the lethal variant of P. yoelii and support the contention of other investigators that a strong Th2 response early in infection is associated with the lethal outcome of malaria.

Animals↗
PubMed1996

Immunogenicity of Leucocytozoon caulleryi sporozoites and their reactivity with specific immune sera.

The immunogenicity of Leucocytozoon caulleryi sporozoites for chickens and their reactivity in vitro with specific immune sera were studied. Almost all of the chickens that had been immunized with the sporozoite antigens survived the sporozoite challenge. The degree of parasitemia observed in the immunized chickens was significantly lower than that found in the nonimmunized chickens. Specific antibodies against sporozoites were tested by the circumsporozoite precipitation (CSP) reaction. Antibodies were demonstrated in the sera of chickens that had been immunized with the sporozoite antigens or chickens that had recovered from a primary infection with L. caulleryi sporozoites. When viable mature sporozoites were incubated in vitro with serum from immune chickens, agglutination and a long, thread-like precipitate at one end of the sporozoite could be seen within a few minutes under a phase-contrast microscope. The effects of specific immune serum on the infectivity of sporozoites were examined by the sporozoite neutralization activity (SNA) test. Sporozoites that had been incubated in vitro with serum from immune chickens lost their infectivity to chickens. The CSP reaction and the SNA test in L. caulleryi infection were stage- and species-specific.

Animals↗
PubMed1996

Characterization of oviductal aromatase in the northern leopard frog, Rana pipiens.

Previous work has shown that the oviduct of the northern leopard frog, Rana pipiens, can convert testosterone to estradiol. The present paper examines the characteristics of the aromatase responsible for this reaction and compares it with human placental aromatase. Microsomes were isolated from the oviducts, and aromatase activity was assayed by a tritiated water release method. The Km and the Vmax for androstenedione were 188.1 +/- 30.2 nM and 1.42 +/- 0.11 fmol of estrogen produced/min/mg protein, respectively. Using the same method, human placental aromatase had a Km of 123.0 nM and a Vmax of 113.57 fmol of estrogen produced/min/mg protein. When tested at four temperatures between 15 and 45 degrees C, the frog enzyme showed maximum activity at 37 degrees C. The enzyme had a broad pH optimum between 7.4 and 10.4. The aromatase inhibitor 4-hydroxyandrostenedione inhibited activity by 20% at 0.3 microM and 40% at 0.5 microM. The present study provides additional evidence that an aromatase is present in the frog oviduct. Characterization of this enzyme revealed similarities to human placental aromatase, but the specific activity was much lower in the frog oviduct.

Androstenedione↗
PubMed1996

Attenuation of Eimeria caviae by selection for precocious development.

An attenuated line of Eimeria caviae was produced by selection for early maturation of oocysts during serial passage in guinea pigs. The prepatent period of the parasite was reduced from 11 to 6 days. Parasites of the precocious line and the parent strain were found in the crypts of the epithelial cells of caecum and colon and were morphologically indistinguishable. The period of development of type I, type II and type III merozoites of the E. caviae precocious line in guinea pigs was similar to that of the parent strain until the 3rd day. The time of the transition from gametocytes to oocysts was 2 days in both the precocious line and the parent strain. The maximum number of oocysts per gram of faeces and the pathogenicity of the precocious line were less than those of the parent strain.

Aging↗
PubMed1996

Alterations in macrophages after exposure to root canal filling materials.

The process of engulfment of overextended root canal filling materials was investigated in rat peritoneal macrophages in vitro. Root canal filling materials tested were Finapec APC, Sealapex, Canals-N, and Canals. The phagocytosis rate of macrophages for the Finapec APC was significantly (p < 0.05) higher than that for other three root canal filling materials. That for Canals was the lowest. About 95% of the cells exposed to Finapec APC were viable at 60 and 120 min. For Canals the percentage was 74% and 63% at 60 and 120 min, respectively. Ruffle formation in macrophages was observed by scanning electron microscopy after exposure to Finapec APC for 60 or 120 min. Many vacuoles were observed in macrophages exposed to Canals for 60 min. It was concluded that the phagocytic rate of macrophages for Canals that showed a strong cytotoxicity was lowest and that the rate for Finapec APC that showed a low cytotoxicity was the highest.

Animals↗
PubMed1996

Gene expressions of c-met and hepatocyte growth factor in chronic liver disease and hepatocellular carcinoma.

BACKGROUND/AIMS: The roles of c-met proto-oncogene and hepatocyte growth factor in human livers have not been shown. METHODS: Gene expressions of both c-met and hepatocyte growth factor were quantified in livers with chronic active hepatitis and in cirrhotic livers with hepatocellular carcinoma as well as in normal controls, using competitive reverse transcription polymerase chain reaction. RESULTS: C-met expression was significantly increased in chronic active hepatitis compared with control livers, and c-met expression in chronic active hepatitis correlated with serum alanine aminotransferase levels. Hepatocyte growth factor expression was increased in some patients with chronic active hepatitis compared with controls, and there was a significant correlation between c-met expression and hepatocyte growth factor expression. On the other hand, in hepatocellular carcinoma tissues, c-met expression was increased in some cases, while that in the surrounding non-carcinomatous tissues was similar to normal controls. Hepatocyte growth factor expression was not detected in the hepatocellular carcinoma tissues and was low in the surrounding non-carcinomatous tissues. CONCLUSIONS: These findings suggest that hepatocyte growth factor may be involved in the regeneration of hepatocytes via paracrine mechanism in chronic active hepatitis, while in regulation of c-met expression in hepatocellular carcinoma tissues may be independent of hepatocyte growth factor stimulation.

Alanine Transaminase↗
PubMed1996

Effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary biliary cirrhosis: a prospective randomized study.

BACKGROUND/AIMS: Although ursodeoxycholic acid is effective for the treatment of primary biliary cirrhosis, some patients do not respond to this treatment. The objective of the present study was to investigate the effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. METHODS: Twenty-two patients with primary biliary cirrhosis treated with ursodeoxycholic acid (600 mg/day) for 30 months were randomly assigned to two groups: group 1, colchicine (1 mg/day) and ursodeoxycholic acid (n = 10); group 2, ursodeoxycholic acid alone (n = 12). RESULTS: In group 1, there were significant decreases in mean serum levels of alkaline phosphatase, total bilirubin, gamma-glutamyltranspeptidase, alanine aminotransferase, aspartate aminotransferase, and IgM, and these changes were more remarkable in those who responded poorly to ursodeoxycholic acid. In contrast, there were no significant changes in those values in group 2. CONCLUSIONS: Additional administration of colchicine to ursodeoxycholic acid may be beneficial for patients with primary biliary cirrhosis, especially those who respond poorly to ursodeoxycholic acid. It is necessary, however, to further confirm the efficacy of colchicine by examining histological changes and following the patients for longer periods.

Aged↗
PubMed1996

Spontaneous conception and intrauterine pregnancy in a symptomatic missed abortion of ectopic pregnancy conceived in the previous cycle.

We encountered a rare case of combined intrauterine and extrauterine pregnancy that occurred following separate spontaneous ovulations. A 33 year old woman visited our hospital with the chief complaint of abdominal pain on April 16, 1993. Her last menstruation was from March 23 for 6 days. However, the urinary human chorionic gonadotrophin (HCG) on April 19 was 1024 IU/l. Pelvic examination and ultrasonography indicated an extrauterine pregnancy, which was confirmed by laparotomy and histological identification of trophoblast cells. The urinary HCG concentration markedly decreased after the operation. However, the HCG level increased again on the fifth post-operative day, and a gestational sac (11 mm) was identified in the uterine cavity on the 11th post-operative day, indicating that this intrauterine pregnancy was established following spontaneous ovulation which occurred before the removal of the extrauterine pregnancy. This case indicates that a combined pregnancy can occur not only after simultaneous multiple ovulations but also after the separate spontaneous ovulations.

Adult↗
PubMed1996

Improvement of peripheral blood lymphocyte subsets in primary biliary cirrhosis after ursodeoxycholic acid therapy.

Immunological abnormalities frequently observed in patients with primary biliary cirrhosis are considered to be related to the pathogenesis of this disease. We performed a prospective trial to evaluate whether immune mechanisms play a role in the effectiveness of ursodeoxycholic acid (UDCA) therapy. Fifteen female patients with primary biliary cirrhosis were followed for 1 year and were then treated with UDCA (600 mg/day) for another year. Laboratory tests, including peripheral blood lymphocyte subsets assessed by dual colour fluorescence analysis using monoclonal antibodies against respective T cell markers, were evaluated at the beginning of the study, at the start of therapy and at the end of therapy. In primary biliary cirrhosis, the proportion of cytotoxic T cells, suppressor inducer T cells and alpha beta-receptor bearing T cells were significantly lower than in healthy controls. No significant changes were observed in the proportions during the year before the therapy. These reductions, however, recovered to normal ranges after 1 year of UDCA therapy. These changes were associated with an improvement in the serum levels of aspartate aminotransferase, alkaline phosphatase, gamma-globulin and IgM. The close correlation between the improvement in the imbalance of lymphocyte subsets after the therapy and the clinical status suggests that an immunological process may play a role in the effectiveness of therapy in primary biliary cirrhosis.

Aged↗
PubMed1996

[Influence of KU-1257 on the recurrence and relapse of acetic acid-induced chronic gastric ulcers in rats].

The influence of KU-1257 on the recurrence and relapse of acetic acid ulcers in rats was investigated grossly and histologically in comparison with that of cimetidine. The ulcer was induced by topical application of glacial acetic acid at the junction of the corpus and antrum on the anterior wall of the stomach. The drug was administered from the 5th to the 153rd day after the ulcer induction and then discontinued to the 238th day. The healing rates of the control groups (control) rose until the 119th day after the ulcer induction, followed by ups and downs. The quality of healing in the regenerated mucosa and the granulation tissue of the healed ulcer was poor, resulting in the recurrence and relapse of ulcers. The recurrence and relapse of ulcers also occurred in the cimetidine groups (CIM). On the other hand, the KU-1257 groups (KU-1257) showed much lower recurrence and relapse rates of ulcers than the control and CIM groups. Moreover, KU-1257, unlike CIM, improved the quality of ulcer healing throughout the period of its administration and even after it was discontinued. These results suggest that KU-1257 improves the quality of ulcer healing, and this may contribute to the low recurrence and relapse rates of ulcers.

Acetates↗
PubMed1996

Endothelin-1-like immunoreactivity and endothelin receptors in the human placenta from normotensive and hypertensive pregnancies.

The levels of endothelin-1-like immunoreactivity (ET-1-LI) and characteristics of endothelin receptors in the chorionic villous tissue of human placenta were determined. The ET-1-LI level in chorionic villous tissue obtained from normal term placenta was 2,450 +/- 940 pg/g wet weight (mean +/- SD, n = 4). Further analysis using gel permeation chromatography and reverse-phase high performance liquid chromatography showed that the main ET-1-LI constituent of ET-1-LI in this tissue was ET-1. Scatchard analysis of [125I]ET-1 binding to the membrane fraction of chorionic villous tissue obtained from term placenta showed high affinity receptor sites with an apparent dissociation constant (Kd) of 23.6 +/- 11.1 pM and a Bmax value of 388 +/- 238 fmol/mg protein (n = 5). The same binding study with [125I]ET 3 showed a Kd of 13.9 +/- 3.8 pM and a Bmax value of 176 +/- 78 fmol/mg protein (n = 5). These results suggest that both ET-A and ET-B receptors (ET-AR and ET-BR) are expressed in chorionic villous tissue. This finding was further confirmed by Northern blot analysis showing the expression of both ET-AR and ET-BR mRNAs in this tissue. ET-1-LI in the umbilical venous plasma of the newborns from women with pregnancy-induced hypertension (PIH) (38.3 +/- 10.4 pg/mL, n = 5) was significantly (P < 0.05) higher than that in the normal newborns from normotensive pregnant women (26.3 +/- 5.2 pg/mL, n = 12). However, in placental chorionic villous tissue obtained from PIH women, both ET-1-LI level and ET binding profile were not different from those in chorionic villous tissue from normotensive pregnant women. These results suggest that the abundant ET-ET receptor system is present in the placental chorionic villous tissue and that this system is not the major factor of the pathogenesis of placental dysfunction occurring in PIH because these systems are similar in normotensive and hypertensive pregnancies.

Chorionic Villi↗
PubMed1996

Cardiorespiratory responses to cycling exercise in trained and untrained healthy elderly: with special reference to the lactate threshold.

The fastest growing age group in the United States and Japan is the elderly. There is a need to develop appropriate exercise training guidelines designed specifically for healthy older persons. Recent reports have shown that the lactate threshold (LT) can be used to evaluate the clinical significance of aerobic power (VO2max) and its effect of exercise training in the elderly. However, there is a lack of research comparing the LT between well-trained and sedentary elderly individuals. Also, the effect of exercise training on the heart rate (HR) at LT needs further investigation. The purpose of this study was to compare the LT levels between the older trained men (T group; n = 72, age = 71.3 +/- 5.8 yr, range 60-85 yr) and apparently healthy but untrained elderly men (U group; n = 172, age = 72.2 +/- 5.7 yr, range 60-93 yr). The LT was measured during an incremental cycle ergometer test. A low relationship was found between VO2 corresponding to LT (VO2LT) and age in the T (r = 0.20, P < 0.05) and U groups (r = 0.43, P < 0.05). A significant difference was found in the VO2LT between the T and U groups. The absolute VO2LT corresponded to approximately 6 and 4 METs for the T and U subjects, respectively. However, there was no significant difference in HR corresponding to LT (HRLT) between the two groups (T; 109 +/- 19 b.min-1, U; 107 +/- 13 b.min-1). The data show that the absolute VO2LT is higher for T than U elderly subjects and is associated with a HR of approximately 108 b.min-1 for both groups. Recommended exercise intensity in terms of HR may not differ between trained and untrained elderly men.

Aged↗
PubMed1996

[Evaluation of risk factors of interferon-associated retinopathy in patients with type C chronic active hepatitis].

The risk factors of retinopathy associated with administration of interferon have not been fully clarified. We prospectively examined the retinal condition in 50 patients with type C chronic active hepatitis during alpha-interferon treatment. 43 patients (86%) were shown to have retinopathy during the course of interferon treatment, and were divided into three groups. Grades I, II and III were patients having a single episode of transient retinopathy with soft exudate or hemorrhage (34%), frequent episodes of retinopathy (42%), and exacerbating retinopathy requiring change or cessation of interferon treatment (10%), respectively. The patients with grade II and III were found to have the first retinal changes within 8 weeks after initiation of the interferon therapy. Early onset of retinopathy and presence of systemic disease such as diabetes mellitus or hypertension were risk factors for serious retinopathy with statistical significance. The grades of retinopathy were also well correlated with dosage and duration of interferon treatment. These results suggest that careful fundus examination is required up to 8 weeks after initiation of interferon treatment, especially for the patients with risk factors such as early onset of retinopathy, presence of systemic diseases, and large dosages and long duration of interferon therapy, in order to prevent serious ocular complications.

Adult↗