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Biomedical subjects

T Kusama

Publications and source records attributed to T Kusama.

At least 73 records · Page 4Linked to original sources
PubMed1989

Combined effects of radiation and caffeine on embryonic development in mice.

The combined effect of radiation and caffeine has been studied in mouse embryos. Radiation and/or caffeine were administered to ICR mice on Day 11 of gestation. Intrauterine death, gross malformation, and fetal body weight were selected as indicators of effects. Doses of whole-body gamma irradiation were 0.5 to 2.5 Gy and those of caffeine were 100 and 250 mg/kg maternal body wt. Intrauterine mortality increased with increasing radiation dose; this trend was more remarkable in combination with caffeine. Gross malformations such as cleft palate and defects of forelegs and hindlegs appeared frequently in the fetuses treated with both radiation and caffeine. Decreased fetal weight was observed even in mice treated with 0.5 Gy of radiation or 100 mg/kg caffeine. There was a linear relationship between dose and reduction of fetal weight. The fetal weight was a sensitive, precise, and easy-to-handle indicator for the effects of growth retardation. Intrauterine mortality and frequencies of cleft palate and defects of forelegs and hindlegs were higher than the sum of those induced by radiation and by caffeine separately. The results indicated that the combined action of radiation and caffeine on intrauterine death and malformations was synergistic.

Abnormalities, Drug-Induced↗
PubMed1988

Location of end-plate region and measurement of conduction velocity of action potential in human muscles by unidimensional latency-topography.

The conduction profile of an action potential elicited by weak voluntary contraction of the m. biceps brachii was graphically displayed by unidimensional latency-topography, UDLT. The end-plate location and conduction velocity (CV) were determined by UDLT. The end-plate location of the m. biceps brachii was measured as 12-15 cm proximal to the epicondylus medialis and remained at the same region independently of the elbow angle. The CV of the action potential of various muscles was also measured in five subjects to reveal inter-muscular variation. The variation in the CV among various muscles in the same subject and that among subjects was not statistically significant. The CV measured ranged from 3.4 to 3.8 m/s.

Action Potentials↗
PubMed1986

Micellar formation of spin-labeled fatty acyl derivatives of lipophilic muramyl dipeptides and their incorporation into liposomal membranes.

A lipophilic muramyl dipeptide (MDP) with a nitroxide moiety in its acyl chain (SL-MDP) and its N-methyl derivative (SL-methyl MDP) were synthesized. The SL-MDPs formed micelles (cmc, 0.1-0.3 mM). The ESR spectra of the SL-MDPs in phosphatidylcholine (PC) liposomes at 25 degrees C consisted of an anisotropic signal and three sharp lines, indicating that both SL-MDPs partitioned between membranes and aqueous phase. The amounts of the SL-MDPs in membranes depended on the phospholipid species and the cholesterol (Chol) content, but no appreciable difference was observed between SL-MDPs. The SL-MDPs partitioned well at 25 degrees C into egg yolk PC liposomes but not into pure dipalmitoylphosphatidylcholine (DPPC), suggesting that the incorporation may be related to the membrane fluidity. Chol enhanced the incorporation into both phospholipids. The mobilities of the SL-MDPs in the membranes were less than that of the corresponding spin-labeled fatty acid. Comparison of the mobilities among SL-MDPs, spin-labeled ganglioside and spin-labeled galactosylceramide showed that the hydrophilicity of the polar group may influence the immobilization of their acyl chains.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

Cross-reactivity between haptenic muramyl di- or tripeptide derivatives and Mycobacterium bovis BCG: potential application for enhancing tumor immunity.

Muramyl di- or tripeptide (MDP or MTP) hapten derivatives bearing various structures were synthesized, and the correlation of these structures with cross-reactivity with Mycobacterium bovis BCG and their applicability to enhance induction of syngeneic tumor immunity were investigated. The cross-reactivity of MDP or MTP haptens to BCG was examined by T-cell proliferation responses of lymph node cells from BCG-primed C3H/He mice in the stimulation with MDP- or MTP-coupled syngeneic cells. A haptenic MDP derivative (designated L4-MDP) stimulated proliferative responses appreciably. Derivatives in which alanine in the peptide portion of L4-MDP was replaced by methylalanine or valine failed to induce stimulation. However, the cross-reactivity with BCG was regained in the MTP derivative that was formed by adding lysine to dipeptide containing methylalanine or valine. Whether this cross-reactive pattern was correlated with enhanced induction of tumor immunity was further investigated. According to the established protocol for the augmented induction of tumor immunity, BCG-primed C3H/He mice were immunized with various haptenic MDP-coupled syngeneic X5563 tumor cells. Immunization with tumor cells conjugating BCG-cross-reactive haptens resulted in enhanced tumor immunity, whereas immunization with tumor cells coupling non-cross-reactive haptens failed to produce anti-X5563 tumor immunity. These results indicate that the peptide portion in these haptenic structures is critical in the generation of BCG cross-reactivity leading to enhanced tumor immunity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

The augmentation of tumor-specific immunity using haptenic muramyl dipeptide (MDP) derivatives. I. Synthesis of a novel haptenic MDP derivative cross-reactive with Bacillus Calmette Guerin and its application to enhanced induction of tumor immunity.

A new haptenic compound, a muramyl dipeptide (MDP) derivative (designated as L4-MDP-ONB) cross-reactive with Bacillus Calmette Guerin (BCG) was synthesized. The cross-reactivity of L4-MDP hapten to BCG was demonstrated from the following evidence; (a) lymph node cells from BCG-primed C3H/HeN mice exhibited appreciable L4-MDP-specific proliferative responses to the in vitro stimulation of L4-MDP-modified syngeneic cells (L4-MDP-self); (b) inoculation of L4-MDP-self into footpads of BCG-primed C3H/HeN mice elicited ample delayed type-hypersensitivity (DTH) responses in vivo as measured by footpad swelling; and (c) BCG-primed mice contained L4-MDP-reactive helper T cell activity which functions to augment the generation of effector T cell responses to cell surface antigens. This crossreactivity between L4-MDP hapten and BCG as measured by the helper T cell activity was applied to enhanced induction of tumor-specific immunity. When BCG-primed C3H/HeN mice were immunized with L4-MDP-modified syngeneic X5563 tumor cells, these mice could generate augmented tumor-specific in vivo protective (tumor neutralizing) immunity as well as in vitro cytotoxic T cell responses. These results indicate the effectiveness of L4-MDP hapten in augmenting tumor-specific immunity. The present approach is discussed in the context of potential advantages of this new hapten for its future application to clinical tumor systems.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Connections of the fronto-parietal operculum and the postcentral gyrus with the posterior ventral thalamic nucleus, especially its medial nucleus, in monkeys.

In 22 crab-eating monkeys (Macaca irus), either lesions or HRP injections were made in the frontol parietal operculum and, for the purpose of contrast, in the postcentral gyrus to observe their fiber connectionl with the posterior ventral nucleus (VP). The exposed opercular part, reported to consist of areas 3b, 1, and 2 showed scanty fiber connections with VP. The buried parietal operculum had connections with the media (VPM) and lateral (VPL) nuclei of VP, corresponding to the second somatic sensory cortex (SII). This cortica area was connected, in VPM, to its ventromedial part, while the base of the postcentral gyrus, the ordinary face area of SI, was connected to its lateral-most part. This suggests that the ventromedial part of VPM is more intimately related to SII, and its lateral-most part to SI. In contrast, the SI and SII areas of VPL overlapped more extensively with each other. The cortical area which received fibers from the parvocellular part of VPM (VPMpc) lay in the frontal operculum, especially in its buried part. This area extended caudally beyond the precentral dimple and included areas 1 and 2 of the buried frontal operculum, indicating that its posterior extent was wider than the pure taste cortical area. Spinothalamic terminations in VPL and the PO nuclear group were discussed in relation to cortical connections of these thalamic nuclei. It was suggested that spinothalamic input could be relayed to both postcentral and opercular cortices. The relation of the spinothalamic input to the PO group appeared to be minor.

Animals↗
PubMed1983

Effects of electrical constants on conduction velocity of action potentials measured with unidimensional latency-topography in frog skeletal muscle fibers.

Conduction velocity (CV) of an action potential recorded from a single muscle fiber of the frog was measured with a new method, unidimensional latency-topography, and electrical membrane constants were determined for the same muscle fiber. CV = 1.96 +/- 0.27 m/sec (n = 52) at about 20 degrees C. Temperature coefficient of CV: Q10 = 2.0. Electrical membrane constants in the same muscle fibers (n = 52): lambda = 3.25 +/- 0.83 mm, tau = 33.4 +/- 14.3 msec, Cm = 6.09 +/- 2.13 mu F/cm2, D = 129.4 +/- 28.9 micron (mean +/- S.D.). The CV decreased linearly with increment of time constant, tau, and membrane capacity per unit area, Cm. The space constant, lambda, and the fiber diameter of the muscle fiber, D, did not correlate with CV. It was concluded that the T-system, which contributes largely to membrane capacity, has a great influence on the CV.

Action Potentials↗
PubMed1982

Pharmacokinetics of neothramycin in animals and man.

The pharmacokinetics of neothramycin (NTM) was performed in mice, rabbits and man. Biological half-life of NTM in man after a 20 mg bolus injection produced an alpha phase half-life of 3.63 minutes, a beta phase half-life of 84.5 minutes and a volume of distribution at a steady state of 50.3 liters/body. Its human half-life was longer than those of adriamycin, mitomycin C and neocarzinostatin, and a little shorter than that of bleomycin. In mice and rabbits, NTM was well distributed in the kidney, urinary bladder, squamous tissues, lung, spleen and gastrointestinal tract and it was rapidly excreted in urine and bile. It was partially absorbed from the gastrointestinal tract. Concentrations of NTM in ascites and pleural fluids in man were also reported.

Adult↗
PubMed1981

Stimulation of nonspecific host resistance to infection induced by muramyldipeptides.

The effect of muramyldipeptide (MDP), N-acetylmuramyl-L-alanyl-D-isoglutamine [MDP(Ala)], and its analogs on bacterial infection was studied using the experimental model of sepsis infection in mice. Injection of MDP(Ala) gave mice definitive protection against E. coli infection, but only partial protection against P. aeruginosa or K. pneumoniae infection. Several factors influencing the protective activity of MDP(Ala) on E. coli infection were studied, and it was demonstrated that the activity was induced by various routes of administration of MDP(Ala), including the oral route, and was markedly influenced by the bacterial inoculum size. It was also shown that the effective dose of MDP(Ala) was 100 micrograms per mouse for intraperitoneal, intravenous or subcutaneous injections and 1,000 microgram per mouse when administered orally. Furthermore, the optimal interval between MDP-treatment and infection was 24 hr when the treatment was carried out before infection. Clearance of bacterial cells in blood was observed after E. coli infection in mice treated with MDP(Ala). The efficacy of MDP(Ala) and two analogs, N-acetylmuramyl-L-valyl-D-isoglutamine [MDP(Val)] and N-acetylmuramyl-L-seryl-D-isoglutamine [MDP (Ser)], was evaluated for the E. coli infection; MDP(Val) was proven to be slightly less active than MDP(Ala), and MDP(Ser) to be the least effective, although MDP(Val) or MDP(Ser) was reported to have higher adjuvanticity than MDP (Ala) for the development of delayed-type hypersensitivity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Stimulation of nonspecific resistance to infection induced by 6-O-acyl muramyl dipeptide analogs in mice.

The experimental system utilized in investigating the correlation between the chemical structures of muramyl peptides and their protective activities in the sepsis type of systemic infections caused by Escherichia coli was applied in evaluating the enhancement of resistance to infection induced by 32 synthetic glycopeptide analogs, including 6-O-acyl derivatives and 1-alpha-O-benzyl derivatives of muramyl dipeptide (N-acetyl muramyl-L-alanyl-D-isoglutamine). In assessing the 6-O-acyl derivatives of muramyl dipeptide, we found that the degree of protective activity was attributable to the kinds of fatty acids introduced. Acylation of the 6-hydroxy group on the muramic acid moiety in muramyl dipeptide with natural mycolic acid or a synthetic fatty acid possessing either an alpha-branched or an alpha-branched, beta-hydroxylated group resulted in a decrease in or a disappearance of the protective activity of muramyl dipeptide. Acylation with a normal fatty acid or an iso fatty acid resulted in a retention or enhancement of muramyl dipeptide activity. The activity of acylated derivatives containing linear fatty acids was stimulated by increasing the chain length up to 18 carbon atoms. The highest degree of protective activity occurred with the derivatives acylated with straight-chain fatty acids, particularly with the derivatives acylated with palmitic acid and arachidic acid. Benzylation of the 1-hydroxy group of muramyl dipeptide resulted in a decrease in or a loss of protective activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

High performance liquid chromatographic assay of neothramycin in biological fluids.

A high performance liquid chromatographic method for quantitative determination of neothramycin in plasma was developed. The procedure involves pretreatments for the removal of endogenous materials in plasma samples and separation on a reversed phase column. The antibiotic was monitored with a fluorescence detector and confirmed by a specific sulfite adduct shift of retention time. A linear response for serum samples containing neothramycin ranging from 50 to 500 ng/ml was obtained. The sensitivity of this method was sufficient to measure neothramycin in human plasma for 120 minutes after a 24 mg/m2 (body surface area) intravenous injection.

Benzodiazepinones↗