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Biomedical subjects

F Okada

Publications and source records attributed to F Okada.

At least 127 records · Page 7Linked to original sources
PubMed1987

Xenogenization of a mouse lung carcinoma (3LL) by transfection with an allogeneic class I major histocompatibility complex gene (H-2Ld).

We investigated the tumorigenicity and immunogenicity of tumor cells transfected with an allogeneic class I major histocompatibility complex gene. A single clone (3LL/3) from a Lewis lung carcinoma in the C57BL/6 strain (H-2b) was cotransfected with a BALB/c genomic clone containing an H-2Ld gene and a bacterial neo gene conferring resistance to G418. Three Ld-positive, three Ld-negative, and two Neor clones were selected by means of a 125I-protein A binding assay using an anti-H-2Ld monoclonal antibody. The antigenic expression of the H-2Ld gene products was only 20-40% on the Ld-positive clones compared with Meth-A tumor cells of BALB/c mice. The 50% lethal tumor dose of these clones in C57BL/6 mice was 5.6 X 10(6) in the Ld-positive clones, but only 1.3 X 10(5) in the 3LL/3 parent clone, 1.2 X 10(5) in the Neor clones, and 2.2 X 10(5) in the Ld-negative clones. The tumorigenicity of the Ld-positive clones was, therefore, reduced to less than 1/40 of that of the parent tumor cells. The decreased tumorigenicity of the Ld-positive clones was abrogated in mice irradiated with 600 rads. After inoculation and spontaneous regression of the viable Ld-positive clone cells, the mice acquired transplantation resistance against the challenge of a parental 3LL/3 tumor. However, the immunogenicity variation between Ld-positive, Ld-negative, Neor, and 3LL/3 parent clones showed no statistical difference. These results indicate that tumor cells transfected with an allogeneic class I H-2 gene can express an H-2 foreign antigen, can regress in syngeneic hosts, and can induce antitumor transplantation resistance against the original tumors, although they are not able to enhance their immunogenicity.

Animals↗
PubMed1987

Changes in the tumorigenic and metastatic properties of tumor cells treated with quercetin or 5-azacytidine.

The effect of quercetin, a flavonoid derivative, on the transplantability (tumorigenicity) and metastatic behavior of mouse tumor cells was studied. BMT-11 c1-9 fibrosarcoma cells were treated in vitro with quercetin, and after cloning by limiting dilution, cell suspensions of each clone were injected subcutaneously (s.c.) into syngeneic C57BL/6 mice at a dose of 2 X 10(5) cells per mouse. Out of 17 clones examined, 8 were nontumorigenic in normal mice ("regressor" clones), whereas these clones were able to grow in immunosuppressed (600-rad-irradiated) mice. Furthermore, 1 out of 9 tumorigenic clones metastasized spontaneously to the lungs despite the very low metastatic potential of the parent BMT-11 c1-9 cells. In contrast, all 15 clones selected from the untreated parental line grew progressively in normal mice with no evidence of metastases. The appearance of both regressor and metastatic clones was also observed after treatment with a DNA hypomethylating agent, 5-azacytidine. These altered phenotypes resulting from treatment with both chemicals, however, were not necessarily stable if maintained in culture for several months. The data suggest that quercetin may be a useful new material for obtaining regressor or metastatic clones from parental tumor lines.

Animals↗
PubMed1987

Enhancement of therapeutic effects of recombinant interleukin 2 on a transplantable rat fibrosarcoma by the use of a sustained release vehicle, pluronic gel.

We have tested the feasibility of pluronic F-127 gel (PLF-127; a polyoxyethylene-polyoxypropylene surface active block copolymer) as a sustained release vehicle for topical administration of interleukin 2 (IL-2) in order to enhance the therapeutic effects of IL-2 against a rat fibrosarcoma, KMT-17. Injection of human DNA recombinant IL-2 (3 X 10(4) units s.c.) in 30% (w/w) PLF-127 into rats provided detectable serum IL-2 levels for up to 10 h, while injection of IL-2 alone provided detectable IL-2 levels for 3 h. When, following s.c. inoculation with 1 X 10(5) KMT-17 tumor cells into rats, IL-2 (6 X 10(4) units/day) in PLF-127 gels was injected s.c. around the growing tumor inoculum every 2 days for 10 days from Day 1 to Day 19, the survival days of rats were more prolonged [mean survival day, 32.3 +/- 5.4 (SD)] as compared with that of rats treated with saline [20.7 +/- 2.1] than mean survival days of rats treated with IL-2 alone [27.3 +/- 4.5] or PLF-127 alone [22.9 +/- 3.3]. Moreover, the span of mean survival days of rats treated with IL-2 in PLF-127 locally (31.7 +/- 5.9) was much longer than that of rats given IL-2 in PLF-127 systemically (22.8 +/- 3.4). By means of a Winn assay, stronger tumor neutralizing activities were observed in regional lymph node cells obtained from tumor bearing rats treated with IL-2 in PLF-127 than were observed in lymph node cells from rats treated with IL-2 alone or PLF-127 alone (percentage of inhibition, 90.3, 12.2, and -15.5%, respectively). The therapeutic effects of IL-2 were thus found to be consistent with the antitumor activity in regional lymph node cells. These results suggest that the enhanced therapeutic effects of IL-2 in PLF-127 are due to enhancement of antitumor immune responses induced by sustained IL-2 activity at the tumor sites.

Animals↗
PubMed1987

Variations in the enzymatic properties of human complement subcomponent C1s by treatment with human plasma kallikrein.

We have investigated the effect of plasma kallikrein digestion upon hydrolytic activities of human C1s. Incubation of C1s (85 kDa) with plasma kallikrein led to progressive cleavages on the heavy chain to yield C1s-K1 (70 kDa) then C1s-K2 (53 kDa). Although these cleavages caused little change in the C2 hydrolytic and esterase activities of C1s, a marked loss in the C4 hydrolytic activity was observed. C1s-K1 and C1s-K2 were purified by DE-52 chromatography and it was found that the proteolysis of C1s into C1s-K1 was accompanied with a decrease in the C4 hydrolytic activity. Although the turnover numbers for the hydrolysis of C4 by C1s-K1 and C1s-K2 were almost the same as that of intact C1s, the Kms for C4 of C1s-K1 and C1s-K2 were found to be increased to 10 times that of intact C1s. This result suggests that the apparent decrease in the C4 hydrolytic activity upon plasma kallikrein digestion of C1s is not due to disruption in the active site but is due to decrease in the affinity between C4 and the C1s derivatives. In support of this assumption, C1s-K1 was found to be devoid of the ability to bind C4b-Sepharose. C1s is capable of forming a dimer through the C1s-binding domain in the N-terminal side of the heavy chain. Although C1s-K1 is still capable of forming a dimer, C1s-K2 fails to form a dimer, suggesting that the N-terminal C1s-binding site is released during cleavage of C1s-K1 into C1s-K2.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Affinity↗
PubMed1987

Intensification of rheological destruction of rat fibrosarcoma KMT 17 cells by elimination of divalent cations.

In an effort to find a method to intensify the rheological destruction of tumor cells, rat fibrosarcoma KMT 17 cells in ascitic form were exposed to rheological stresses in test solutions; modified Eagle medium with EDTA, and phosphate buffer solution without divalent cations or with verapamil. KMT 17 cells were exposed to a uniform shear stress produced by the rotation of a rotating cone plate viscometer for 1 to 2 hours and to the strong deformation by the passage through Nuclepores of 10, 8 and 5 micrometer. KMT 17 cells suspended in the test solutions were more effectively destroyed by the stresses than those suspended in normal solutions containing divalent cations without any other calcium-suppressing agents. These results suggest that the elimination of divalent cations and/or the block of calcium ion channels of cell membranes intensify the rheological destruction of tumor cells migrating in the circulatory system.

Animals↗
PubMed1987

[Five male cases of wrist-cutting with suicidal intent].

Five male student cases of wrist-cutting with suicidal intent were reported. They had only one or two wrist-cutting episodes. They are compared to cases with wrist-cutting syndrome reported by Rosenthal et al. Four of the five cases occurred during a period with depressive symptom, and the fifth during a period with hallucinatoric and delusional state. One case was diagnosed as a schizophrenic, another as depressive and the other three had no clear diagnosis. Two of the five cases had one depressive or schizophrenic parent, and two other cases had one suicidal or accidental death of brother or father. Three of the five cases had tried other methods of suicide, drugs, electricity and gas. However, the prognosis of all five cases is good, three graduating and two remaining in the university. The male cases here have only one or two wrist-cutting episodes different from female cases where a larger number of episodes is common. However, it is necessary to remember that diagnosis for both males and females is very difficult and other symptoms are similar.

Adult↗
PubMed1987

Two cases of transient partial amnesia in the course of transient global amnesia.

In the course of transient global amnesia, two patients showed symptoms of transient partial amnesia. Close observation showed that at some time during the episode the patients had some degree of nonverbal memory, which recovered earlier than verbal memory. Careful observation of the progression of symptoms during an episode of transient global amnesia may often reveal symptoms of transient partial amnesia.

Amnesia↗
PubMed1986

Desensitization of beta-adrenergic receptor-coupled adenylate cyclase in cerebral cortex after in vivo treatment of rats with desipramine.

Continuous treatment (1-10 days) of rats with desipramine (10 mg/kg, twice per day) caused desensitization of the beta-adrenergic receptor-coupled adenylate cyclase system of cerebral cortical membranes. The decrease in the isoproterenol-stimulated adenylate cyclase activity was more rapid and greater than the decrease in the number of beta-adrenergic receptors in membranes during treatment of the membrane donor rats with desipramine, indicating that the desensitization occurring at an early stage of the treatment was not accounted for solely by the decrease in the receptor number. Neither the guanine nucleotide regulatory protein (N) nor the adenylate cyclase catalyst was impaired by the drug treatment, since there was no decrease in the cyclase activity measured in the presence or absence of GTP, guanyl-5'-yl-beta-gamma-imidodiphosphate [Gpp(NH)p], NaF, or forskolin. Gpp(NH)p-induced activation of membrane adenylate cyclase developed with a lag time of a few minutes in membranes from control or drug-treated rats. The lag was shortened by the addition of isoproterenol, indicating that beta-receptors were coupled to N in such a manner as to facilitate the exchange of added Gpp(NH)p with endogenous GDP on N. This effect of isoproterenol rapidly decreased during the drug treatment of rats. Thus, functional uncoupling of the N protein from receptors was responsible for early development of desensitization of beta-adrenergic receptor-mediated adenylate cyclase in the cerebral cortex during desipramine therapy.

Adenylyl Cyclases↗
PubMed1985

Deranged metabolism of cyclic nucleotides in liver diseases.

To clarify the factor(s) responsible for changes in the plasma cyclic GMP concentration in liver diseases, we measured the plasma levels of cyclic GMP, along with cyclic AMP, in various clinical stages of chronic liver diseases and acute hepatitis. The level of cyclic GMP was found to increase significantly in the early stage of acute hepatitis, in the decompensated stage of liver cirrhosis, and in malignant diseases. In the former two states, it is postulated that decreased hepatic mass is responsible for the changes in the plasma cyclic GMP concentration. The retention rate of indocyanin green (ICGR15) was highly correlated with the plasma cyclic GMP level. The result suggests that the determination of plasma cyclic GMP is useful as an index of the reserve function of the liver in disease states.

Carcinoma, Hepatocellular↗
PubMed1985

Depression after treatment with thiazide diuretics for hypertension.

The authors reports eight cases of depression induced by thiazide diuretics prescribed for hypertension and discusses possible mechanisms behind this action. The side effects of thiazide diuretics may be overlooked when they are used with other hypertensives known to cause depression.

Adult↗
PubMed1983

Plasma cyclic nucleotide responses to psychological stress in normal and neurotic subjects.

The mirror drawing test (MDT) was performed to induce acute psychological stress in 10 normal volunteers and 23 neurotic patients. Plasma cAMP and cyclic guanosine 3',5'-monophosphate (cGMP) were determined serially before, during, and after the test. In controls, the MDT caused a significant increase in the plasma cAMP level, whereas no change was observed in plasma cGMP. This increase was suppressed by simultaneous administration of propranolol, although it was not affected by simultaneous injection of phentolamine. In neurotic patients, the instruction for the MDT itself resulted in increased cAMP and cGMP levels, although there were no further significant increases during and after the MDT. The results indicate: 1) the increase in plasma cAMP during the MDT reflects a beta-adrenergic stimulation; 2) in neurotics, the response of cAMP and cGMP to the MDT is different from the controls. This difference may be a potential parameter in the diagnosis and discrimination of neurotic disorders.

Adolescent↗
PubMed1983

Plasma cyclic AMP responses to adrenaline administration in patients with spinocerebellar degeneration, bronchial asthma, and diabetes mellitus--a preliminary report of a clinical test for detecting beta-adrenergic dysfunctions.

Plasma cyclic AMP responses to adrenaline administration in normal volunteers, patients with spinocerebellar degeneration, bronchial asthma, pulmonary emphysema, and diabetes mellitus were studied. Intramuscular administration of low doses (0.1--0.4 mg/person) of adrenaline caused a dose-dependent increase in plasma cyclic AMP. The increase in cyclic AMP was completely prevented by propranolol, while it was not affected by phentolamine or atropine. In patients with spinocerebellar degeneration, the concentrations of plasma cyclic AMP both before and after adrenaline administration were lower than in normal subjects. In asthmatic patients, the plasma cyclic AMP increase after adrenaline administration was smaller than that of the healthy controls. The plasma concentration of cyclic AMP in patients with insulin-dependent diabetes reached the peak level more slowly than in diabetic patients with dietary control alone. Examining changes in the plasma cyclic AMP level after adrenaline administration appears to be a useful means for assessing the degree of beta-adrenergic dysfunction.

Adult↗
PubMed1983

[Argyll-Robertson and other pupillary abnormalities in neurosyphilis--with special reference to the detection of peripheral lesions].

The pupillary disturbances in twenty five neurosyphilitic patients were investigated. Miotic, light-rigid pupils, i.e., Argyll-Robertson pupils were found in only three of these patients. One of three patients showed unilateral Argyll-Robertson pupil. Irregular margins of the iris were associated with these miotic, light-rigid pupils. Abnormal striations of the iris were found in four of eight non-miotic (medium size), light-rigid pupils. Cocaine or ephedrine produced dilatation of two of these pupils, and, following this mydriasis, the pupils were capable of constricting to light. These abnormalities of the iris were not found in slightly light-reactive pupil. The light-rigid pupil induced by long-term administration of neuroleptics and antiparkinson drug in comparison with Argyll-Robertson pupil was also mentioned, and the findings of many authorities who have proposed a peripheral nerve pathogenesis of the Argyll-Robertson syndrome were reviewed.

Antipsychotic Agents↗