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Biomedical subjects

H Oikawa

Publications and source records attributed to H Oikawa.

At least 73 records · Page 4Linked to original sources

Transfer of antibodies to kittens from mother cats chronically infected with Toxoplasma gondii.

By indirect immunofluorescence assay, anti-Toxoplasma gondii antibody levels were examined in fetuses and kittens born from chronically infected cats. Titer of anti-T. gondii IgG in sera of kittens born from infected cats was significantly high on the seventh day post-birth, and decreased to a serologically non-detectable level at 8-12 weeks post-birth under continuous suckling of maternal milk. Littermates nursed by a non-infected cat showed a faster rate of IgG antibody depletion. In sera of fetuses obtained from infected cats, anti-T. gondii IgG titer was lower than that of offspring born from infected cats. Anti-T. gondii IgM titer was non-detectable in sera of all kittens and fetuses. Kittens born from infected cats inoculated with T. gondii oocysts on Day 35 after birth shed oocysts and showed a transient increase of anti-T. gondii IgM titer. Findings in this study suggest that anti-T. gondii antibody IgG in kittens is transferred mainly via colostrum and the kittens that receive maternal anti-T. gondii antibodies develop inadequate resistance to T. gondii infection.

Animals↗

[Pharmacokinetic studies on continuous intraportal 5-fluorouracil infusion].

Pharmacokinetics of 5-FU administered by continuous intraportal infusion were studied by infusing 5 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg of 5-FU, respectively, into the ileocecal vein for an hour. Blood samples were collected from portal vein, femoral vein and liver, and small intestine specimens were obtained at proper intervals. The rabbits were sacrificed at 120 minutes from the start of 5-FU infusion. The results were as follows: Extremely high concentrations of 5-FU in the portal vein, femoral vein and liver tissue were observed in the 5-FU group infused with 40 mg/kg. This phenomenon was suggested to rely on the effect by which the 5-FU catabolic enzyme, dihydrouracil dehydrogenase, was saturated with a large inflow of 5-FU. FdUMP concentration of the liver was lower than that of the small intestine in all groups. These results suggest that a large dose of 5-FU infusion is effective to increase the FdUMP concentration in the liver with continuous intraportal 5-FU infusion.

Animals↗

[Experimental study on the effectiveness of PET tumor images for cancer diagnosis].

Positron emission tomography (PET) with 2-deoxy-2 [18F] fluoro-D-glucose (18FDG), a structural analog of glucose, allows tumor images to be obtained, based on increased glycolysis in cancer cells. In the present study, in order to confirm the effectiveness of 18FDG-PET tumor images for cancer diagnosis, 18FDG tumor uptake values were measured in human gastric cancer xenografts in nude mice. Firstly, comparison of 18FDG uptake and histological grade in four gastric cancers showed that 18FDG uptake increased with loss of differentiation. Secondly, reduction of 18FDG uptake values after administration of anticancer drug was found to correlate with chemosensitivity to anticancer agent, and the values were reduced prior to suppression of tumor growth. These data suggest that 18FDG-PET tumor images may provide reliable indications for assessment of the histological grade of the tumor and the efficacy of cancer chemotherapy.

Adenocarcinoma↗

Accumulation of 2-deoxy-2[18F]fluoro-D-glucose in human cancers heterotransplanted in nude mice: comparison between histology and glycolytic status.

UNLABELLED: The success of tumor imaging with PET and 2-deoxy-2-fluoro[18F]-D-glucose (18FDG) is based on preferential accumulation of 18FDG in tumors. METHODS: Fluorine-18-FDG uptake was measured in nine human cancers heterotransplanted in nude mice and compared with histologic subclassification. RESULTS: Mean 18FDG uptake by the human cancers was considerably less than that by the host's heart, but values at 60 min after injection were about 2.5 times as high as the liver and kidney, about two times as that for the muscle and about six times that for the blood. Comparison of 18FDG uptake and histological grade in four gastric, two pancreatic and three colonic cancers showed that 18FDG uptake increased with loss of differentiation. CONCLUSION: This nude mice model system is useful for studying correlations between physiological and morphological parameters of heterotransplanted human cancers.

Animals↗

Segregation of cerebrorubral and cerebellorubral synaptic inputs on rubrospinal neurons of fetal cats as demonstrated by intracellular recording.

Cerebrorubral and cerebellorubral inputs are localized to distal dendrites and somata of red nucleus neurons in adult cats, respectively. To examine if this segregation is established early in development, we performed intracellular recording from rubrospinal neurons of fetal cats aged from embryonic day 58 to 65. Stimulation of the contralateral cerebellar nuclei evoked excitatory postsynaptic potentials (EPSPs). EPSPs were also induced by stimulation of the ipsilateral pericruciate cortext but they were much slower in time course and smaller in amplitude compared to cerebellar ones. We suggest that cerebrorubral and cerebellorubral synapses are segregated on soma-dendritic membrane of rubrospinal neurons early in development.

Animals↗

Protective immune response of Isospora felis-infected mice against Babesia microti infection.

Protective response against Babesia microti was studied in Isospora felis-infected mice. Isospora felis-infected mice which were exposed to B. microti on the 28th day post-infection showed absolute resistance against Babesia microti. Interestingly, these mice showed no anti-B. microti antibodies. Mice that received spleen cells from I. felis-infected donors that were subsequently exposed to B. microti showed lower peak parasitemia (10.3% +/- 2.6) compared to those mice that received normal spleen cells (60.9% +/- 15.0), and no spleen cells at all (47.3% +/- 8.5). Treatment of I. felis-infected mice with monoclonal antibodies against L3T4+ cells resulted to a depression of their resistance to B. microti, as clearly manifested by high levels of parasitemia. Findings of the present study demonstrate the role of cell mediated immunity, specifically by L3T4+ T-cells induced by I. felis infection, in providing mice protection against B. microti.

Animals↗

[Arterial infusion chemotherapy of 5-FU and leucovorin for patients with liver metastases from colorectal cancer].

Fifteen patients with liver metastases from colorectal cancer were treated by arterial infusion of 5-FU and leucovorin. Two regimens were performed. One was weekly bolus infusion of leucovorin following bolus infusion of 5-FU (bolus group), the other was 5 days continuous infusion of 5-FU and leucovorin in 3 weeks (continuous group). One PR was obtained both in the bolus group and in the continuous groups. The objective response rate was 11% in the bolus group and 20% in the continuous group. The one- and 2-year survival rates for these patients were 40% and 0% in the bolus group, and 80% and 60% in the continuous group, respectively. These results suggest that continuous arterial infusion of 5-FU and leucovorin was more effective than individual bolus arterial infusion of leucovorin and 5-FU for patients with liver metastases from colorectal cancer.

Adult↗

[Lymphoscintigraphy with 99mTc-DTPA-HSA in the diagnosis of protein-losing gastroenteropathy].

We evaluated the diagnostic capability of technetium-99m-diethylene triamine pentaacetic acid-human serum albumin (99mTc-DTPA-HSA) lymphoscintigrapy in a patient with protein-losing gastroenteropathy. 99mTc-DTPA-HSA (total 740 MBq) was injected subcutaneously into the digital webs of the both feet. With a gamma camera, whole-body and abdominal lymphoscintigrams were obtained after the injection of the radioisotope: early images and delayed images taken 5-15 min and 50-60 min, respectively, after the injection. A few days later, the dynamic lymphoscintigraphy was also performed. Lymph fluid leakage into the small bowel and the sites of the leakage were detected. It was concluded that lymphoscintigraphy with 99mTc-DTPA-HSA was a useful diagnostic tool in patients with protein-losing gastroenteropathy.

Adult↗

Inhibitory effects of beta-alanine on the vagal efferent and afferent excitatory responses of the stomach to stimulation of vagal trunk in cats.

The effects of beta-alanine on the electrically evoked vagal efferent (hexamethonium-sensitive initial excitatory response) and afferent (hexamethonium-resistant delayed excitatory response) responses of the cat stomach were studied. beta-alanine (30 to 300 micrograms/kg, i.v.) dose-dependently inhibited both the efferent and afferent response. The IC50 values of beta-alanine on the efferent and afferent response were 296 +/- 65 micrograms/kg and 128 +/- 35 microgram/kg, respectively. Maximal inhibitory effects of beta-alanine (300 micrograms/kg, i.v.) appeared about 1 hr after the injection. Glycine and taurine (100 to 10,000 micrograms/kg) did not affect these responses. Treatment with hexamethonium (10 mg/kg, i.v.) prevented the efferent response, but augmented the afferent response. The treatment with hexamethonium abolished the inhibitory effect of beta-alanine on the afferent response. Both picrotoxin (100 and 500 micrograms/kg, i.v.) and bicuculline (2000 micrograms/kg, i.v.) antagonized the inhibitory effects of beta-alanine on the vagal efferent and afferent responses of the stomach. The present experiments clearly demonstrated that beta-alanine inhibited both the vagal efferent and afferent excitatory responses of stomach to electrical stimulation of vagal trunk in cats.

Animals↗

Altered cell tropism and cytopathicity of feline immunodeficiency viruses in two different feline CD4-positive, CD8-negative cell lines.

Two interleukin-2-dependent feline CD4-positive and CD8-negative cell lines, MYA-1 and the newly established FeL-039, were used as host cells for infection with feline immunodeficiency virus (FIV). All FIV strains used, the Petaluma strain and several new isolates, were highly cytopathic to MYA-1. In contrast, the kinetics of FIV replication in FeL-039 differed greatly depending on the strain tested, i.e., noninfectious strain, highly cytopathic strain, and less cytopathic strain producing a persistent state for a long period. It appears, therefore, that cell tropism for FIV differed with each FIV strain tested even in T-cell lines showing similar cell surface phenotypes. Cytopathicity of FIV is evidently due to both the FIV strain and the host T cell.

Animals↗

[Pharmacokinetic studies of continuous and bolus intraportal 5-fluorouracil infusion].

We studied the pharmacokinetics of continuous and bolus intraportal 5-FU infusion. In continuous intraportal infusion group, 20 mg/kg of 5-FU was infused into ileocecal vein for an hour and the same dose was infused bolusly in bolus intraportal infusion group. Blood samples were collected from portal vein continuously and liver specimens were obtained continuously. The rabbits were sacrificed at 180 minutes from the start of infusion of 5-FU and small intestine was obtained. The results were as follows: A significantly higher concentration of 5-FU in the portal vein was observed in the continuous intraportal infusion group compared with the one-shot infusion group. But the elimination rate of 5-FU was more rapid after cessation of infusion in the continuous infusion group. The rate of FdUMP elimination in the liver tended to be lower in bolus intraportal infusion. The FdUMP concentration in the small intestine was higher in the continuous intraportal infusion group than in the bolus infusion group. In the continuous intraportal infusion group, the FdUMP concentration in the liver was lower than in the small intestine. This depended on the effect of the 5-FU catabolic enzyme, dihydrouracil dehydrogenase, which is contained in the liver in large quantities. The results suggest that in order to increase the FdUMP concentration in the liver with continuous intraportal 5-FU infusion, suppression of the effect of this enzyme is necessary.

Animals↗

Synapses formed by ectopic corticofugal axons: an electron microscopic study of crossed corticorubral projections in kittens.

The corticorubral projections in newborn kittens are bilateral, while the projections are unilateral in adults. We addressed the question whether or not the crossed corticorubral projection in kitten forms synaptic contacts in the red nucleus. The neurons in the sensorimotor cortex of the kitten were labeled by Phaseolus vulgaris-leucoagglutinin or biocytin. Electron microscopic observations revealed that corticofugal axons form synapses both in the contralateral and the ipsilateral red nucleus; most of them were on small postsynaptic profiles, possibly dendritic spines or distal dendrites.

Animals↗

Functional reinnervation of carotid artery by implanted preganglionic trunk in the cat.

The preganglionic trunk of the superior cervical ganglion was implanted chronically into the carotid artery. A helical strip of the carotid artery with nerve was prepared, and electrical stimulation of the nerve caused a definite contraction. Part of the contraction was attenuated by phentolamine, and the remaining part of the contraction was nearly abolished by tubocurarine but not by hexamethonium and atropine. The present results clearly demonstrate that the carotid artery is reinnervated by preganglionic cholinergic fibers.

Animals↗

[Phase I trials--clinical studies of antineoplastic agents].

The establishment of the starting dose and the dose escalation are the principal issues of the Phase I trials of anticancer agents. We report the procedures and results of the Phase I studies we participated in Japan in the 1980's concerning 17 intravenous anticancer agents. The drugs indicated a correlation between the mouse LD10 and the man MTD (maximum tolerated dose) in mg/m2. Median mouse LD10 (135 mg/m2) approximated to median man MTD (137 mg/m2) in mg/m2. One fifth of the mouse LD10 was lower than the man MTD. Therefore, as recognized at the 23rd Annual Congress, Japan Society for Cancer Therapy, the lower one of either 1/5 the mouse LD10 or 1/3 the dog TDL (toxic dose low) in mg/m2 has to be determined as safe starting dose. The modified Fibonacci search scheme has been generally adopted for the dose escalation. 14 applicable drugs were examined including 7 drugs in the early 1980's and 7 drugs in the late 1980's. The real number of steps that reached the man MTD was compared to the number of the steps taken in the dose escalation by the Fibonacci's method. The real steps were more than the Fibonacci's ones in the late 1980's. It showed the tendency of a more careful and safer dose escalation, however, to put it critically, the dose escalation was not efficient enough. It is expected that the contradictory problem between safety and efficacy in the Phase I studies will be solved by developing methods like pharmacokinetic study in animals and man.

Antineoplastic Agents↗