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Biomedical subjects

J Shimizu

Publications and source records attributed to J Shimizu.

At least 271 records · Page 15Linked to original sources
PubMed1986

Non-H-2-linked genetic regulation of cytotoxic responses to hapten-modified syngeneic cells. I. Non-H-2-linked Ir gene defect expressed on T cells is not predetermined at the stage of bone marrow cells.

Spleen cells from C3H/He or BALB.K mice immunized to the newly synthesized amino-reactive hapten 5-sulfo-1-naphthoxy acetic acid N-hydroxysuccinimide ester (AED-NH2) were stimulated in vitro with AED-NH2-modified syngeneic cells. After 5 days of culture, effector cells were assayed for their cytotoxic activity against AED-NH2-modified target blast cells. C3H/He and BALB.K mice exhibited the respective high and low anti-AED-NH2 cytotoxic T lymphocyte (CTL) responses. This contrasted with the observation that both of these H-2k strains generated potent CTL responses against aminoreactive haptens, e.g., trinitrophenyl (TNP). Because C3H.SW and BALB.B strains, which are the H-2b counterpart of the above two strains, also represented the respective high and low responders to AED-NH2 hapten, this hapten model enabled us to investigate cellular mechanisms underlying the above non-H-2-associated genetic regulation of CTL responses (C3H vs BALB non-H-2 backgrounds). The results demonstrated that there was no detectable difference between C3H/He and BALB.K strains in the lysability of target cells and the ability of stimulating cells to activate primed spleen cells. Anti-AED-NH2 CTL responses were only marginal when antigen-presenting cells (APC) were eliminated from the primed spleen cells of high responder C3H/He or (C3H/He X BALB.K)F1 mice. The addition of APC to cultures free of APC regained an appreciable CTL response in C3H/He or (C3H/He X BALB.K)F1 mice, irrespective of whether APC were derived from high (C3H/He) or low (BALB.K) responders. We have also demonstrated that allogeneic radiation bone marrow chimera (BALB.K----C3H/He) exhibited a CTL response comparable to that induced by C3H/He mice, whereas the reverse direction of allogeneic chimera (C3H/He----BALB.K) induced a marginal CTL response. These results indicate that this non-H-2-associated Ir gene defect is expressed on T cells (CTL precursors and/or helper T cells) rather than APC, and that this T cell defect is not predetermined at the level of bone marrow cells. The results are discussed in the light of the genetic and cellular mechanisms underlying non-H-2-linked Ir gene control.

Animals↗
PubMed1986

Susceptibility to ischemic insult in hypertensive rats: correlation between degree of ischemia and hypertension.

The Wistar rat, with a blood pressure range of 120-160 mmHg, and two strains of spontaneously hypertensive rats (SHR), stroke-prone (SHRSP, range 210-270 mmHg) and stroke-resistant (SHRSR, range 160-240 mmHg), were used to determine the degree of damage after ischemic insult induced by bilateral carotid artery ligation (BLCL). The survival rate and McGraw Stroke Index correlated well with the degree of hypertension. After BLCL, impairment of cerebral blood flow is abrupt and residual flow is near zero in rats with initial blood pressures greater than 200 mmHg. A markedly deteriorated aerobic metabolism, as measured by the concentrations of ATP, c-AMP and lactate, is seen to precipitate in rats with initial blood pressures greater than 180 mmHg and severe edema occurs if the pressure is more than 160 mmHg. The degree of hypertension that produces high vulnerability to stroke and severe damage to the brain after ischemic insult is indicated as beginning at about 180 mmHg.

Adenosine Triphosphate↗
PubMed1986

[Effect of long-term prior antihypertensive treatment on cerebral ischemia induced by bilateral common carotid artery ligation in SHRSR].

The susceptibility to cerebral ischemia was studied in stroke-resistant spontaneously hypertensive rats (SHRSR) treated by a long-term antihypertensive treatment, and compared with untreated SHRSR and Wistar rats (WR). Male SHRSR, aged 8 weeks, were divided into two groups and a long-term antihypertensive treatment for 4-6 weeks was started on one group (treated SHRSR: T-SHR) while the other group was left untreated as control (untreated SHRSR: U-SHR). The changes of blood pressure were checked on these rats. The prior treatment of hypertension was achieved by administration of hydroflumethiazide (120 mg/kg/day) and captopril (15-30 mg/kg/day) orally for 4-6 weeks by mixing in drinking water. All the experiments were performed at the age of 12-16 weeks and WR of similar age served as normotensive untreated control. Cerebral ischemia was induced by bilateral common carotid artery ligation (BLCL) and blood pressure was always checked before BLCL. The survival ratio was observed from 1 hour to 24 hours after BLCL. The regional cerebral blood flow (rCBF) were measured before and 4 hours after BLCL periodically. The brain energy metabolites were measured 4 hours after BLCL. rCBF were measured at the thalamus by the hydrogen clearance method. ATP concentrations were determined by luciferine-luciferase method, c-AMP was measured by RIA and lactate by enzymatic method. The brain water content was measured by freeze-dry method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Arachidonic acid-induced brain ischaemia: different severity between stroke-resistant spontaneously hypertensive rats and Wistar-Kyoto rats.

A thrombo-embolic stroke model was produced by the internal carotid artery (ICA) infusion of arachidonic acid (AA). The differences in responses to AA ICA infusion were investigated in stroke-resistant spontaneously hypertensive rats (SHRSR) and Wistar-Kyoto (WKY) rats. The SHRSR showed a higher mortality, more severe brain oedema and brain metabolic impairment, more prominent elevation of TXB2 and 6-keto-PGF1 alpha. Electron microscopic observation revealed more severe endothelial damage, mitochondrial swelling and perivascular oedema and earlier thrombus formation in SHRSR than in WKY rats.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Expression of H-2 antigens and inducibility of antitumor immune responses in various tumor cell clones established from methylcholanthrene-induced fibrosarcomas.

A large number of fibrosarcoma cell lines was established in vitro from a tumor mass induced freshly by inoculating 3-methylcholanthrene (MCA) subcutaneously (sc) into C3H/HeN mice, and more than five clones were isolated from each cell line by the limiting dilution technique. The present study investigated a) qualitative and quantitative comparison of the immunogenicity [tumor-associated transplantation antigen (TATA) activity] of different tumor clones and b) the relationship between such immunogenicity and the expression of H-2 class I antigens. When TATA were compared between different clones from the same tumor, these TATA were revealed to be cross-reactive to each other. On the other hand, the comparison of TATA between clones from different tumors demonstrated the existence of individually unique TATA in these clones. In addition to qualitative heterogeneity of TATA from different tumors, the magnitude of immunogenicity was also heterogeneous in the individual clones established. Whether or not such quantitative heterogeneity of immunogenic strength was related to the expression of H-2 (class I) antigens was examined by flow microfluorometry studies using anti-H-2k antibodies. The results demonstrated that there was no correlation between TATA activity capable of inducing in vivo tumor resistance and the expression of H-2 antigens. This contrasted with parallelism between the expression of H-2 antigens and inducibility of cytotoxic T lymphocytes (CTL) or lysability of tumor cell clones by CTL. These results are discussed in the context of the cellular mechanism of tumor cell eradication in vivo and the regulation of cell surface H-2 expression in vitro and in vivo.

Animals↗
PubMed1986

[Effect of bilateral common carotid artery ligation on prostaglandin levels (TXA2, PGI2) in spontaneously hypertensive rats (SHRSP, SHRSR) and normotensive rats (WKY)].

Three different levels of global forebrain ischemia were induced in rats and their plasma levels of Thromboxane B2 (TXB2) and 6 Keto PGF1 alpha were determined to investigate the relation between severity of ischemia and eicosanoid production. Ischemia stimulates the activity of cellular lipase whose actions cause deacylation of brain phospholipids and release of free fatty acids. Arachidonic acid (A.A.) is one of the predominant fatty acids which is liberated in brain after ischemia. A.A. is the primary substrate for the synthesis of prostaglandins (PGs), Thromboxane A2 (TXA2) and Prostacyclin (PGI2), which play an important role in regulation of platelet aggregation and vasotonus. Thromboxane is a potent platelet aggregator and vasoconstrictor. On the other hand, PGI2 has the opposite nature. Therefore it can be considered that PGs and moreover, the balance of TXA2 and PGI2 may have an intimate relation to the development of cerebral ischemia. Three different levels of ischemia were produced by bilateral carotid artery ligation (BLCL) using three kinds of rats with different blood pressure ranges, namely, SHRSP (Stroke-prone spontaneously hypertensive rats), SHRSR (Stroke-resistant spontaneously hypertensive rats) and WKY (Wistar kyoto rats). It is known that higher pressure groups suffer severe ischemia by BLCL procedure. Hypertensive rats (SHRSP, SHRSR) were originally produced from WKY. The experimental animals used were about 300 gr and 16 weeks old male rats. The plasma and brain TXB2 and 6 Keto-PGF1 alpha, stable metabolites of TXA2 and PGI2 were measured by radioimmunoassay. The chronological changes of brain and plasma PGs levels after ischemia using SHRSR were also investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1986

[A neurochemical study of rat brain maldevelopment induced by MAM treatment at different stages of gestation].

The regional levels of several cell marker proteins in the brain and the ability of operant discrimination learning on a multiple fixed ratio (FR), fixed interval (FI) schedule were determined in rats with microencephaly induced by prenatal treatment with methylazoxymethanol (MAM), an antimitotic agent, on the 11 th to 13 th days (Group A) or on the 15 th day (Group B) of gestation. The cell marker proteins were determined with a sensitive enzyme immunoassay. Neuron-specific enolase (NSE; gamma gamma-enolase) had a significantly lowered level in the neocortex anterior in Group A. Non-neuronal enolase (NNE; alpha alpha-enolase) was significantly reduced in the superior colliculus, lateral geniculate body and optic nerve, but increased 1.5 fold in the retina in Group A. S-100b protein, a marker of astroglial cells, showed no significant change. As for the learning performance, the Group B animals showed an elevated behavioral activity and made evident discrimination between the FI and FR schedule. But Group A animals had prolonged FR components requiring responses to light on, and their spontaneous activity counts recorded by Automex showed an inhibition of behavior in light environments. These findings suggest a causative role of some developmental abnormality in the central visual system, indicated by the aberrant cell marker levels, in the disturbed learning ability of the Group A animals.

Abnormalities, Drug-Induced↗
PubMed1986

[Protective effect of thromboxane A2 synthetase inhibitor (trapidil) on acutely-induced cerebral ischemia].

The experimental study presented was undertaken to evaluate the role of thromboxane A2 contributing to aggravating cerebral ischemia, and to examine the effect of a thromboxane A2 synthetase inhibitor, trapidil on cerebral ischemia. Cerebral ischemia model was induced in 16 week old spontaneously hypertensive rats (SHR) by bilateral common carotid artery ligation (BLCL). Two doses of trapidil 15 mg/kg was intraperitoneally administered one dose 2 hr before and one dose 15 min after BLCL in SHR. While control animals only underwent BLCL. Brain tissue metabolites such as ATP, lactate and pyruvate, brain water content and plasma thromboxane B2 and 6 Keto PGF1 alpha were determined 3 hr after BLCL. Scanning electron microscopic observations were also recorded. ATP concentrations were 1.36 +/- 0.23 n moles/mg wet tissue in the trapidil treated group, 0.61 +/- 0.26 n moles/mg wet tissue in the control group, the difference between the treated and the control being significant (P less than 0.001). Lactate concentrations were 4.70 +/- 1.20 n moles/mg wet tissue in the treated group, 12.17 +/- 8.53 n moles/mg wet tissue in the control group, the difference between the treated and the control being significant (P less than 0.02). Pyruvate concentrations were 0.59 +/- 0.11 n moles/mg wet tissue in the treated group, 0.43 +/- 0.16 n moles/mg wet tissue in the control, the difference was also significant (P less than 0.05). Average water content was 78.87 +/- 0.59% in the treated group, 79.82 +/- 0.33% in the control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1985

[Clinical value of postoperative chemotherapy for non-small cell lung cancer--with special reference to long-term combined chemotherapy combined with immunotherapy].

The main reason for unfavourable surgical outcome of lung cancer is latent distant metastases over looked during surgery, which ultimately cause recurrence, or death of the patients even in cases undergoing curative surgery. This fact necessitates the indispensable use of systemic adjuvant therapy in patients under going surgery for lung cancer. There have been mary reports concerning the clinical efficacy of surgical adjuvant chemotherapy for non-small cell lung cancer using various kinds of drugs in various treatment modalities, but the results have been controversial. During the past eleven years, we have used postoperative chemotherapy in three ways over three different periods: in the earliest period, short-term combined chemotherapy (STCC) was used, in the middle period, intermittent long-term combined chemotherapy (ILTCC) was used in combination with immunotherapy for a randomized group, and in the latest period, when continuous long-term combined chemotherapy (CLTCC) with immunotherapy was employed. A comparison was then made between these three kinds of treatment groups. In Comparing of the results obtained for the earliest and middle periods, ILTCC showed a significantly improved beneficial effect over STCC in terms of further increased survival rate. Furthermore, by randomized study, it was clarified that the favourable effect of ILTCC was further improved by concomitant use of immunotherapy. CLTCC with immunotherapy carried out in the latest period seemed to be prevent early recurrences in patients with stage I or II who underwent curative surgery, even though a short-term observation period of for 20 months was employed. It is conceivable that the latest treatment modality used will exerted best the most favourable beneficial effect in comparison with the two early treatments. A review of the literature was presented along with a discussion of the clinical value of chemotherapy and immunochemotherapy as a surgical adjuvant.

Adenocarcinoma↗
PubMed1985

[Effects of S-adenosyl-L-methionine on experimental cerebral ischemia].

Effects of S-adenosyl-L-methionine (SAMe) on experimental cerebral ischemia were investigated using two different ischemic models. Cerebral energy metabolites (ATP, lactate, c-AMP) and brain water content were measured. It is reported that SAMe accelerates synthesis of phosphatidyl choline and increases erythrocyte membrane fluidity. Complete ischemia was produced by heart excision using wistar kyoto rats. SAMe (100 mg/kg, I.P.) was administered twice at one hour and immediately before inducing ischemia. The brain of rats were irradiated by microwave to stop the enzyme activity exactly 60 seconds after inducing ischemia and brain energy metabolites were measured. Recirculation model was produced by one hour recirculation following two hours ischemia induced by clipping of bilateral common carotid arteries using stroke-prone spontaneously hypertensive rats. SAMe (100 mg/kg, I.V.) was administered twice one hour after clipping and ten minutes after recirculation. The brain metabolites and water content were measured one hour after recirculation. In the complete ischemia, ATP and c-AMP levels were statistically high in the SAMe treated group compared to the untreated group (vehicle). But there was no statistical difference in lactate between the treated group and the untreated group. In the recirculation model, lactate elevation was suppressed in the SAMe treated group compared to the vehicle group with statistical difference, but there was no difference in ATP and c-AMP. Also, there was no difference in water content between the treated and the untreated group. SAMe protected energy failure in ischemia and accelerated recovery from ischemia. It is indicated that this agent is beneficial for treatment of cerebral ischemia in the acute stage.

Acute Disease↗
PubMed1985

The influence of thymic abnormalities on the development of autoimmune diseases.

The relationship between thymic abnormalities and development of autoimmune diseases was studied in MRL/l and NZB/NZW F1 (NZB/W F1) mice. Thymic abnormalities, including plasma cell infiltration into the thymus, were observed in 25% of MRL/l mice as early as 1 mo and in all mice after 2.5 mo. The thymic abnormalities preceded both infiltration of lymphoid cells into the kidney and salivary glands, and also preceded an increase in the titer of circulating immune complexes (CIC). When MRL/l and NZB/W F1 mice were divided into two groups for each strain at the critical age when the mice had begun to show thymic abnormalities, the group with abnormal thymuses showed more marked pathological findings in other organs and a higher level of CIC than the group with more normal appearing thymus. In addition, the group with abnormal thymus demonstrated lower responsiveness of their lymphocytes in mixed-lymphocyte culture than the group with normal thymus. Thymus grafts from donors of autoimmune or non-autoimmune strains into nude mice revealed that thymic functions, reconstitutive of immunologic parameters of nude mice, are rapidly lost with age. These results suggest that morphological and functional abnormalities of the thymus are involved in the pathogenesis of autoimmune diseases.

Age Factors↗
PubMed1984

Effects of water temperature and weight of wheel load on water wheel turning behavior of imipramine administered mice.

This experiment investigated the effect of imipramine on water wheel turning behavior in relation to the water temperature and the wheel load. It was shown that the higher the water temperature, the more the mice rotated the wheel, and the greater the wheel load, the less mice rotated it. However, these factors did not reduce the effect of imipramine, which increased the number of responses. It was suggested that the water wheel test shows promise as a screening test for antidepressants.

Animals↗
PubMed1984

[Decreased beta-adrenergic receptor binding in the rat's brain on the activity-stress paradigm].

It was recently suggested that beta-adrenergic receptor binding in the rat brain was decreased by repeated electric shocks. In order to examine whether this phenomenon is observed under another stressor, the activity-stress paradigm was used in the present study. Rats were divided into 3 groups of AS, DC and AC.AS was housed in a cage with a running wheel and fed 1 hour daily. DC was fed in the same condition as AS, but housed in a cage without the wheel. AC was housed in a running wheel cage and fed in standard condition. AS exhibited excessive running and subsequently revealed sharp reduction of activity, body weight and food consumption on 7 or 8th experimental day. When these decrement was seen in AS, each rat was decapitated and beta-receptor binding was measured. AS showed excessive stomach ulcers, but DC and AC didn't. beta-Receptor binding in the cerebral cortex of AS was significantly lower than that of other groups. These results indicate that beta-receptor binding in the rat cortex was also decreased by the activity-stress paradigm.

Animals↗
PubMed1984

The activation of mice's behavior and reduction of brain beta-adrenergic receptor binding following repeated administration of antidepressant drugs.

In view of the fact that antidepressant drugs have almost no effect on a normal person's emotion and behavior, it seems necessary to examine their effects on animal behavior under abnormal, or stressful conditions. When mice were put into a water wheel apparatus, they tried to escape from the water by turning the wheel. This "wheel-turning behavior" was activated by repeated doses of imipramine or amitriptyline. The increase was paralleled by a reduction of brain beta-adrenergic receptor binding. It was speculated that chronic doses of antidepressants would increase escape behavior in mice when they were placed in a critical situation. The causal relationships between this behavioral change and beta-receptor function in brain remains to be further examined.

Administration, Oral↗