Search PubMed⌕ Search

Biomedical subjects

T Imamura

Publications and source records attributed to T Imamura.

At least 523 records · Page 29Linked to original sources

Investigations into the mechanism of immunosuppression caused by acute treatment with O,O,S-trimethyl phosphorothioate: generation of suppressive macrophages from treated animals.

At concentrations normally found in the spleen, macrophages from animals treated with O,O,S-trimethyl phosphorothioate (OOS-TMP) for 24 hr were previously shown to be immunosuppressive (Rodgers et al., 1985b). In addition, it was shown that macrophages from OOS-TMP-treated animals had a diminished capacity to present antigen (Rodgers et al., 1985c). In this report, it was shown that lowering the number of splenic adherent cells (95% macrophages by morphology) utilized in cell-mixing experiments to reconstitute the nonadherent splenic populations returned the humoral immune response to control levels. One day following acute administration of OOS-TMP, resident peritoneal cells were able to suppress the proliferation of P815 tumor cells. In addition, proliferative responses to concanavalin A and lipopolysaccharide were decreased at suboptimal concentrations of mitogen. Fresh supernatants from splenocytes cultured for 24 hr from OOS-TMP-treated animals blocked the generation of a humoral immune response. However, supernatants from splenocytes of control animals generated in the same manner did not block the generation of a humoral immune response. These data suggest that OOS-TMP induced the generation of suppressive macrophages which may potentially act through the release of labile factors which block proliferation or antigen- or mitogen-induced lymphocyte stimulation.

Animals↗

Effects of O,S,S-trimethyl phosphorodithioate on immune function.

The effect of acute administration of 20-80 mg/kg O,S,S-trimethyl phosphorodithioate (OSS-TMP) to C57BL/6 female mice on the murine immune system was determined. The parameters examined to evaluate overt toxicity of the compound included body weight, plasma cholinesterase levels, splenic nucleated cell number and thymic weight and nucleated cell number. Acute administration of 60 or 80 mg/kg OSS-TMP led to a 75 or 63% decrease, respectively, in plasma cholinesterase levels and a decrease in thymic size. At a dose of 80 mg/kg OSS-TMP, the animals also exhibited some lethargy and body weight loss. Below 60 mg/kg OSS-TMP, no overt toxic manifestations were observed. These studies were carried further to determine the effect of OSS-TMP on the generation of in vivo primary and in vitro secondary cellular and humoral immune responses. At nontoxic doses of the compound, i.e. 20 and 40 mg/kg OSS-TMP, the in vivo generation of a primary cytotoxic T lymphocyte (CTL) response to alloantigen was significantly elevated, but this response was unaffected following restimulation of the splenocytes by alloantigen in vitro. The generation of an in vivo primary and in vitro secondary humoral responses to sheep red blood cells (SRBC) was elevated following a single dose of 40 mg/kg OSS-TMP. Administration of toxic doses of OSS-TMP, i.e. 60 and 80 mg/kg, did not alter the ability of splenocytes to generate a primary or secondary CTL response, but suppressed the generation of humoral immune responses. These results differ significantly from those observed in a similar system following acute administration of a structural analog, O,O,S-trimethyl phosphorothioate which was previously shown to have potent immunosuppressive activity at nontoxic doses.

Animals↗

Polydactyly of the hands and feet.

Polydactyly of the hand, of the foot, and of the hand combined with the foot were studied. As noted in previous reports of polydactyly, inherited cases represent about 10% of polydactyly of the hand or foot, and unilateral involvement is more common than bilateral. In 495 cases of polydactyly 27 patients had polydactyly of the hands and feet. The extra digits in 21 of those 27 were in the same digital rays of the hand and foot. There were 14 inherited cases (51.9%) and most were an autosomal dominant, but some were an autosomal recessive. Both hand and/or feet were involved in 22 cases. Most cases of preaxial polydactyly of the hand combined with central polydactyly of the foot were sporadic and unilateral. All cases of both preaxial and postaxial (polyaxial) polydactyly were inherited and bilateral. Two pairs of sisters had the same clinical features. The parent (mother or father) also had the same deformities in the inherited cases.

Female↗

Nonoperative treatment of camptodactyly.

Twenty-four patients with camptodactyly of their small fingers were treated with a dynamic splint. Most of the patients could extend the proximal interphalangeal (PIP) joints within a few months by using the dynamic splint 24 hours a day. After almost full extension of the proximal interphalangeal joint was achieved, splinting for 8 hours a day produced good final results. However, after the splint was removed, contracture tended to recur. Although further studies are needed to determine the optimum termination of treatment, in our opinion it should be when the growth plate is closed, and longitudinal growth of the finger no longer occurs.

Adolescent↗

Hyperventilation thallium-201 myocardial imaging for the diagnosis of vasospastic angina.

In seven patients with vasospastic angina, a transient myocardial perfusion defect was demonstrated on Tl-201 myocardial imaging after hyperventilation (HV). The development of spasm on one or more coronary arteries after HV was confirmed by later coronary arteriographic studies, with the perfusing area of the coronary arteries being compatible with the scintigraphic location of the defect. Repeated 12-lead electrocardiograms failed to establish the diagnosis in one of the seven patients. It is concluded that HV Tl-201 myocardial imaging provides invaluable information in establishing a diagnosis of vasospastic angina.

Adult↗

Expression of hepatitis B virus middle and large surface antigen genes in Saccharomyces cerevisiae.

The hepatitis B virus genome carries the surface antigen (SAg) gene and an open reading frame that encodes two SAg-related polypeptides: SAg with a 55-amino-acid N-terminal extension polypeptide and SAg with a 174-amino-acid N-terminal extension polypeptide. These are termed middle S and large S, respectively. These polypeptides or their glycosylated derivatives have been detected in Dane particles, but their chemical and biological properties have remained largely unknown because of their limited availability. We attempted to produce these proteins in Saccharomyces cerevisiae by placing the coding regions under the control of the promoter of the yeast glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Yeast cells carrying middle S and large S coding sequences produced 33,000- and 42,000-dalton products, respectively, each of which reacted with anti-S antibody and bound to polymerized human serum albumin, in accordance with the known properties of pre-S proteins from particles in human sera (K. H. Heermann, U. Goldmann, W. Schwartz, T. Seyffarth, H. Baumgarten, and W. H. Gerlich, J. Virol. 52:396-402, 1984; A. Machida, S. Kishimoto, H. Ohnuma, K. Baba, Y. Ito, H. Miyamoto, G. Funatsu, K. Oda, S. Usuda, S. Togami, T. Nakamura, Y. Miyakawa, and M. Mayumi, Gastroenterology 86:910-918, 1984). The middle S polypeptide is glycosylated and can be assembled into particles whose size and density are similar to those of SAg. However, this polypeptide was highly susceptible to proteolytic degradation into 29,000- and 26,000-dalton polypeptides, of which only the former retained the binding activity to polymerized albumin. The large S polypeptides are nonglycosylated, relatively stable, and do not seem to assemble into particles by themselves.

Cloning, Molecular↗

Relationship of glucagon suppression by insulin and somatostatin to the ambient glucose concentration.

The glucagon-suppressing activity of insulin and somatostatin were compared at high and low glucose concentrations. In normal dogs made hyperglucagonemic by phloridzin pretreatment, insulin and somatostatin suppressed glucagon at rates of 47 +/- 8 and 35 +/- 8%/h (NS), respectively, despite profound hypoglycemia. In severely hyperglycemic alloxan-diabetic dogs, insulin and somatostatin suppressed glucagon at rates of 48 +/- 13 and 54 +/- 6%/h, respectively, not different from the nondiabetic dogs. After phloridzin pretreatment to eliminate hyperglycemia in the diabetic dogs, insulin and somatostatin suppressed 51 +/- 8 and 31 +/- 10%/h (NS), respectively. Glucose infused in the phloridzin-pretreated insulin-deprived group suppressed glucagon only partially; insulin was required to reduce it further. We conclude that insulin and somatostatin suppress glucagon at similar rates irrespective of ambient glucose levels, and that diabetic hyperglucagonemia represents the summation of stimulation by insulin lack minus suppression by the associated hyperglycemia.

Animals↗

[Digital subtraction angiography of the coronary artery: evaluation of morphological aspects].

The usefulness of digital subtraction angiography (DSA) in coronary angiography was evaluated in terms of its ability to delineate the coronary artery and aortocoronary (A-C) bypass grafts. First, 59 intra-arterial injections of contrast media were made for 23 patients with ischemic heart disease. With aortic root injection, the proximal coronary artery was moderately well visualized, but visualization of the peripheral arteries was inadequate. By selective coronary injection, good images of the coronary arteries were obtained using small quantity of contrast media; however, detailed evaluations of the degrees of stenosis and collateral circulation were difficult, because of limitations in spatial resolution and misregistration artifacts due to cardiac pulsations. In addition, the patencies of 12 A-C bypass grafts were evaluated using intravenous (IV-) DSA for three cases and intraaortic (IA-) DSA for five cases. Ten grafts were shown to be patent. With IV-DSA, the graft was imaged as superimposed on the ascending aorta. In IA-DSA, a small (4F) catheter was introduced via the right brachial artery and advanced to the ascending aorta where an aortic root injection was performed. With aortic root injection, not only the anastomotic portion but also the distal native coronary artery were visualized. Lateral and severe left anterior oblique projections were best to visualize the grafts. IA-DSA using 4F catheter could be performed for outpatients without complications. The patency of a graft can be evaluated with the time density curve between two points in the graft, and the coronary blood flow can be calculated using the time density curve measurements and the diameter of the artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗

Effect of induction of T-cell-dependent antibody with sheep red blood cells on P-450-dependent and -independent xenobiotic metabolizing enzymes.

The effect of an antigenic challenge with sheep red blood cells (SRBC) on the activities of cytochrome P-450-dependent and -independent xenobiotic metabolizing enzymes and on lipid peroxidation in the liver was investigated. The studies were carried out using three mouse strains of C57B1/10 and three strains of C3H backgrounds which are cogenic, differing genetically at the H-2 complex. The basal levels of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (7-Ec) were different among congenic strains. The activity of 7-Ec was lower in C3H background mice than in B10 background mice. Similarly, the difference due to the strain and the H-2 locus was detected in the activities of P-450-independent enzymes such as malathion and diethyl succinate carboxylesterases, glutathione S-transferase, and epoxide hydrolases in microsomal and cytosolic fractions. The degree of immune responsiveness in these mice was determined by a plaque forming cell assay. Within the same background, the H-2b mouse strain was a high responder and the H-2k a low responder to SRBC. However, treatment with SRBC had no significant depressive effect on P-450-dependent enzyme activities except in C3H/He. Activity of AHH was suppressed in C3H/He mice. Treatment with SRBC had no effect on P-450-independent enzyme activities except for malathion carboxylesterase: the activity was increased in C3H/He and C3H.JK, whereas it was decreased in B10. The basal level of lipid peroxidation was lower in C3H/He and C3H.JK. The treatment produced a significant enhancement in lipid peroxidation in C3H/He, B10 and B10.BR (P less than 0.05) with a concomitant increase in xanthine oxidase activity (P less than 0.05). Thus, the present study revealed that a specific antigenic challenge, unlike non-specific immunostimulants (e.g. poly IC, endotoxin), does not necessarily inhibit P-450-dependent xenobiotic metabolizing enzymes even though antigen challenge increased XO activity and lipid peroxidation. The possible roles of an increase in lipid peroxidation and xanthine oxidase activity in immune response to SRBC and xenobiotic metabolizing enzymes are discussed.

7-Alkoxycoumarin O-Dealkylase↗

Influence of H-2 haplotypes on poly IC induction of xanthine oxidase and poly IC induced decreases in P-450 mediated enzyme activities.

Polyriboinosinic-polyribocytidylic acid (poly IC), a potent interferon inducer, induced xanthine oxidase 24 hours after treatment with 5 mg/kg ip to different degrees among four H-2 congenic mice (P less than 0.05): B10 (H-2b: 236 +/- 27% of the control value) greater than B10.RIII (H-2r: 171 +/- 29%) = B10.F (H-2n: 161 +/- 12%) greater than B10.BR (H-2k: 136 +/- 15%). Aryl hydrocarbon hydroxylase (AHH) activity showed an inverse correlation with inducibility of xanthine oxidase (r = -0.71, P less than 0.01). However, there were no significant changes in activities of heme pool associated enzymes, such as catalase, tryptophan pyrrolase and d-aminolevulinic acid synthase in these mice. H-2 haplotype seems to have an influence on poly IC induction of xanthine oxidase thereby causing a decrease in AHH.

Animals↗

Treatment with poly I.C. enhances lipid peroxidation and the activity of xanthine oxidase, and decreases hepatic P-450 content and activities in mice and rats.

Treatment of mice and rats with polyriboinosinic acid-polyribocytidylic acid (poly I.C., 5 mg/kg i.p.), a potent interferon inducer, decreased hepatic cytochrome P-450 system content and activities without influencing P-450-independent xenobiotic metabolizing enzymes. Treatment with poly I.C. decreased the content of P-450 by 28% in mice (P less than 0.05) and 30% in rats (P less than 0.05) but did not alter the activity of cytochrome c reductase. With treatment of poly I.C., the activity of XO increased 87% in mice (P less than 0.01) and 30% in rats (P less than 0.01). Lipid peroxidation was enhanced by 82% in mice (P less than 0.01) and 95% in rats (P less than 0.05). These results raise the possibility that a part of the depression of P-450 system content and activities by poly I.C. might be caused by enhanced lipid peroxidation associated with increased activity of XO.

Animals↗