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Biomedical subjects

M Shinkai

Publications and source records attributed to M Shinkai.

At least 73 records · Page 4Linked to original sources
PubMed1995

Inhibitory effects of d-nicotine on the responses evoked by 1-isomer in trachea and bronchus isolated from guinea-pig and rabbit.

1. The effects of d-nicotine on the responses induced by 1-isomer were studied in tracheae and bronchi isolated from guinea-pigs and rabbits. In guinea-pigs trachea 1-nicotine produced a biphasic response consisting of initial contraction and following relaxation. In other airway preparations 1-nicotine produced only contraction. 2. d-Nicotine did not produce any responses except for the case of guinea-pig trachea. d-isomer produced only relaxation and relative potency was approximately 0.44 in guinea-pig trachea. 3. Pretreatment with d-nicotine (30-300 microM) reduced concentration response curves for 1-isomer in a non-competitive manner in all preparations used in this study. 4. 1-nicotine at the concentration of 3 microns, which did not produce any response itself, reduced the concentration response curve of 1-nicotine in guinea-pig trachea. 5. Inhibition by d-nicotine or 1-nicotine (3 microM) of the concentration-response curve of 1-nicotine may be due to desensitization of nicotine receptors.

Animals↗
PubMed1995

Molecular detection of human cytomegalovirus and determination of genotypic ganciclovir resistance in clinical specimens.

The data presented in this article demonstrate how the polymerase chain reaction (PCR) can be used to detect human cytomegalovirus (HCMV) DNA in the plasma and cerebrospinal fluid (CSF) of infected individuals. Detection of HCMV DNA in plasma of transplant recipients and persons infected with human immunodeficiency virus identifies people with acute visceral disease and those at highest risk for development of HCMV disease. The detection of HCMV DNA in CSF is of particular help in identifying persons with HCMV-related central nervous system disease. In addition, specific mutations within the UL97 region, which encodes for a HCMV protein kinase, have been found to confer ganciclovir resistance and can be detected in plasma and CSF by direct sequencing of PCR products. These data will help provide tools for clinicians to better diagnose, manage, and treat persons with HCMV disease.

AIDS-Related Opportunistic Infections↗
PubMed1995

Antibody-conjugated magnetoliposomes for targeting cancer cells and their application in hyperthermia.

Magnetoliposomes for hyperthermia treatment of cancer were prepared by coating phospholipid on to magnetite particles. The optimum phospholipid composition for dispersibility was a phosphatidylcholine/phosphatidylethanolamine ratio of 2:1. The average size of the magnetoliposomes, which were aggregates of 10 nm core magnetite particles, was about 80 nm. The magnetoliposomes were coated with hydrazide pullulan to stabilize the phospholipid capsules and provide an anchor for the immobilization of antibodies. By this method, 90-180 molecules of a monoclonal antibody were immobilized on to a magnetoliposome particle. When the antibody-conjugated magnetoliposomes were incubated with cancer cells, they were adsorbed on to the cell surface and incorporated by the cells about 12 times more effectively than the control after 4 h. The amount of incorporated magnetite was 0.61-3.6 pg/cell, depending on the antigen-antibody system. The heating properties of the magnetoliposomes were also measured and found to vary with the size of the core magnetite.

Antibodies, Monoclonal↗
PubMed1995

Quantitation of human cytomegalovirus (HCMV) DNA in cerebrospinal fluid by competitive PCR in AIDS patients with different HCMV central nervous system diseases.

The current study was designed to quantitate human cytomegalovirus (HCMV) DNA in cerebrospinal fluid (CSF) of persons with AIDS with specific HCMV-related CNS disease. DNA present in CSF obtained from AIDS patients was initially detected by a qualitative PCR procedure and then quantitated using a competitive PCR assay. In a group of 21 AIDS patients with HCMV-related CNS disease, 12 patients with HCMV polyradiculopathy had a mean +/- SEM of 11,982 +/- 4,480 copies/microliters in their CSF compared to 1,747 +/- 929 for 9 patients with HCMV encephalitis p = 0.017). Of the 14 patients with > 1,000 copies/microliters of HCMV DNA in CSF, 11(79%) had HCMV polyradiculopathy including all 3 with > 10,000 copies/microliters. Ganciclovir treatment of 3 patients with HCMV-related CNS disease was associated with a decline in HCMV DNA detectable within CSF. These data indicate that quantities of HCMV DNA in CSF are higher in persons with HCMV-related polyradiculopathy than encephalitis, and that quantitation of HCMV DNA can be useful in monitoring antiviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed1995

[Treatment of aneurysm of aortic arch using selective cerebral perfusion].

The objective of this study is to evaluate safety and efficacy of the selective cerebral perfusion (SCP) for an adjunct to perform operation of aortic arch aneurysms. From November 1982 to June 1993, surgical treatment of aneurysm of aortic arch using SCP was performed in 22 patients. The hospital death was accounted in 5 cases (23%), the intraoperative stroke was observed in 3 cases (14%) and these patients died. The cause of intraoperative stroke was cerebral hypoperfusion due to multiple sclerosis of intracranial arteries or insufficient SCP. Variables of an increased operative risk seemed to be older age (over 70 y.o.) and rupture. SCP time more than 120 minutes did not promote the operative risk. Cerebral hypoperfusion was directly responsible for not only intraoperative stroke, but also operative death. Therefore, SCP seems effective and safe if hypoperfusion is prevented.

Aged↗
PubMed1995

Preparation and characteristics of magnetite-labelled antibody with the use of poly(ethylene glycol) derivatives.

With a view to the application of magnetic particles in cancer thermotherapy (hyperthermia), methods of preparing a bio-applicable magnetite with targeting activity towards cancer cells were investigated, and the properties of the material examined. Poly(ethylene glycol) (PEG)-magnetite consisting of magnetite (Fe3O4) and PEG with terminal carboxy or amino groups was prepared. Monoclonal antibody was then immobilized covalently on to the PEG-magnetite. Among three different immobilization methods employed, the highest immobilization density of 492 mg of protein/g of PEG-magnetite was achieved by using water-soluble carbodi-imide. However, with respect to residual antibody activity, only the method in which IgG sugar chains were oxidized to give aldehyde groups for coupling to N-terminal PEG-magnetite was satisfactory, with about 60% of the activity surviving. The immobilization density by this method (109 mg of protein/g of PEG-magnetite) was also sufficiently high. The product, termed magnetite-labelled antibody, was of sub-micrometre size and showed easy magnetophoresis. It was further elucidated that cancer-specific magnetite-labelled antibody bound to cancer cells at an amount of 50 mg of magnetite/cm3 of cells. The PEG-magnetite generates heat at an evolution rate of 31.5 W/g, and the amount adsorbed to the cells was calculated to be high enough to heat a tumour 1 cm in diameter to more than 42 degrees C in 30 s under an alternating magnetic field [at an intensity of 572 Oe (approx. 45.5 kA/m) and a frequency of 240 kHz]. This magnetite-labelled antibody is expected to be applicable clinically as a therapeutic agent for the induction of hyperthermia.

Antibodies, Monoclonal↗
PubMed1994

Pre- and postjunctional actions of endothelin in the rat iris sphincter preparation.

Effects of endothelins (ETs) were studied in the rat iris sphincter preparation. Three peptides (ET-1, ET-2 and ET-3) caused contractile responses, and the rank order of agonist potency was: ET-1 = ET-2 > ET-3. The concentration-response curve to ET-1 was shifted to the right by the ETA receptor antagonist cyclo [D-Asp-L-Pro-D-Val-L-Leu-D-Trp] (BQ-123: 10(-7) M), the pA2 value of which was 7.41 +/- 0.09 (n = 4). ET-1 and ET-3, at the concentration of 10(-9) M, potentiated cholinergic contractions evoked by electrical field stimulation (5 and 20 Hz) without affecting the postjunctional sensitivity to carbachol. This potentiating effect was not influenced by BQ-123 (10(-6) M). The ET-evoked percentage increase in the stimulation-induced contraction observed at 5 Hz was significantly greater than that at 20 Hz. A release of immunoreactive ET was detected when the preparation was stimulated at 20 Hz (1.81 +/- 0.36 pg/sphincter n = 6). ET release evoked by 20 Hz stimulation was completely abolished by tetrodotoxin (10(-7) M). In conclusion, ET interacts with two different receptor types, ETA and non-ETA receptors (probably ETB) which exist post- and presynaptically at cholinergic neuroeffector junctions of the rat iris preparation. Stimulation of ETA receptor results in a direct muscle contraction and non-ETA receptor activation facilitates the acetylcholine output from cholinergic nerve endings. It is suggested that ET released from a tetrodotoxin-sensitive site is involved in the modulation of acetylcholine release in the rat iris sphincter preparation.

Amino Acid Sequence↗
PubMed1994

Effects of ageing on regional differences in the contractile responses to acetylcholine and neurokinin A in rabbit airway.

1. Experiments were designed to study the effects of ageing on muscarine and NK2 receptor mechanisms in the three different regions of rabbit airway. 2. The pD2 value of acetylcholine changed with age in three different regions while that of carbamylcholine, which is resistant to acetylcholinesterase, did not. 3. The pD2 values of neurokinin A and the activity of protease, a degradative enzyme, changed with age. However, by the pretreatment with phosphoramidon, a protease inhibitor, the regional difference and age related change of the pD2 value of neurokinin A disappeared. 4. In conclusion, the observations about age related changes and regional differences of pD2 value of acetylcholine and neurokinin A were due to the difference of their degradative enzyme activities.

Acetylcholine↗
PubMed1994

Non-invasive Doppler technique for detection of flow velocity in left internal mammary artery grafts.

The capability of Doppler to detect patency of left internal mammary artery grafts through the supraclavicular approach was evaluated. A total of 37 patients with a left internal mammary artery graft to the left anterior descending artery were divided into three groups, according to postoperative coronary angiographic studies. Group 1 comprised 20 patients with no significant stenosis of the left internal mammary artery and subtotal or total obstruction in the left anterior descending coronary artery proximal to the anastomotic site. There were ten patients with no significant stenosis of the left internal mammary artery and 75% stenosis of the left anterior descending coronary artery in group 2. Seven patients with significant stenosis of the left internal mammary artery formed group 3. Analysis of the flow velocity pattern in the left internal mammary artery graft included: (1) systolic peak velocity (SPV), (2) diastolic peak velocity (DPV), (3) systolic time velocity integral (SI), (4) diastolic time velocity integral (DI), (5) diastolic peak velocity/systolic peak velocity and (6) diastolic time velocity integral/diastolic time velocity integral+systolic time velocity integral. There were no significant differences in systolic peak velocity and systolic time velocity integral between the three groups. The diastolic peak velocity and diastolic time velocity integral were greater in group 1 than in groups 2 (P < 0.05, P < 0.01) and 3 (P < 0.05). The diastolic peak velocity/systolic peak velocity and diastolic time velocity integral/diastolic time velocity integral+systolic time velocity integral ratios in group 3 were significantly smaller than in groups 1 and 2 (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1994

[An operative case of aortic regurgitation due to quadricuspid valve].

A case of quadricuspid aortic valve is described. A 43-year-old man admitted because of chest oppression on exercise. He had a ejection systolic murmur and decrescendo diastolic murmur. Electrocardiogram revealed severe left ventricular hypertrophy. Echocardiogram showed dilated left ventricle and supernumerary cusp between the right and left coronary cusp. Aortogram revealed quadricuspid aortic valve with grade 4 aortic regurgitation. At operation, quadricuspid aortic valve in which supernumerary cusp between right and left coronary cusp was smaller was found. Four cusps were excised and replaced with 23 mm Medronic-Hall prosthesis. His postoperative course was uneventful. Quadricuspid aortic valve has been extremely rare. Twenty operative cases has been reported. The clinical feature was presented.

Adult↗
PubMed1993

Effect of tachykinins on the acetylcholine output stimulated by nicotine from guinea-pig bladder.

Effects of tachykinins on contractile responses and acetylcholine release evoked by nicotine were determined by isotonic transducer and radioimmunoassay. A sympathetic nerve blocker guanethidine and tachykinin antagonist, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-substance P (rpwwL-SP) partially inhibited the acetylcholine release evoked by nicotine to much the same degree. In preparations treated with rpwwL-SP to block the tachykinin receptors, guanethidine had no effect on the response to nicotine and vice versa, suggesting an exclusive contribution of the sympathetic nerve communications to the action of tachykinins. A concentration response curve to neurokinin A but not SP methyl ester or Tyr0-neurokinin B was shifted to the left after cholinesterase inhibition with methanesulphonyl fluoride (MSF) and was partially inhibited by atropine. In the presence of guanethidine, an acetylcholine output by nicotine was facilitated in the presence of neurokinin A (10 nM) but not SP methyl ester (10 nM) or senktide (10 nM). These results indicate that acetylcholine release evoked by nicotine is increased by the coordinated action of sympathetic nerves and tachykinins. Tachykinin receptor subtype involved in acetylcholine release is NK2.

Acetylcholine↗
PubMed1993

Direct synaptic connections between thalamocortical axon terminals from the mediodorsal thalamic nucleus (MD) and corticothalamic neurons to MD in the prefrontal cortex.

A combined anterograde axonal degeneration with ibotenic acid and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) retrograde tracing study revealed that some degenerating thalamocortical axon terminals from the mediodorsal thalamic nucleus (MD) directly formed asymmetrical synaptic contacts predominantly with dendritic spines of apical dendrites of WGA-HRP-labeled corticothalamic projection neurons to MD in the prelimbic cortex of the rat. This result suggests that there is a monosynaptic feedback loop from and to MD via deeper layer neurons in the prelimbic cortex.

Animals↗
PubMed1993

Tachykinin receptors of the NK2 type involved in the acetylcholine release by nicotine in guinea-pig bladder.

1. The effects of guanethidine and tachykinins on nicotine- and electrical stimulation-induced cholinoceptor responses were studied in isolated urinary bladder from the guinea-pig. 2. Acetylcholine release and the contractile response stimulated by nicotine were partially reduced by a sympathetic nerve blocker, guanethidine. Neurokinin A (but not substance P methyl ester or senktide) enhanced both acetylcholine release and contraction by nicotine in the presence of guanethidine. 3. Frequency-contraction curves (1 to 50 Hz) for electrical field stimulation (EFS) were partially reduced by atropine (1 microM), and after desensitization to alpha,beta-methylene adenosine 5'-triphosphate, the atropine-resistant contraction to EFS was completely abolished. Guanethidine, the tachykinin antagonist [D-Arg1, D-Pro2, Trp7,9, Leu11]-substance P and application of neurokinin A or substance P did not change the contractile response to EFS. Preganglionic nerve stimulation (5 Hz and 20 Hz) also evoked a similar response to EFS and was not influenced at all by guanethidine or neurokinin A. 4. We conclude that the ability of nicotine to release acetylcholine is enhanced both by endogenous tachykinins (probably released from sympathetic nerves) and by exogenously applied tachykinins as a result of interaction with NK2 receptors in the urinary bladder.

Acetylcholine↗
PubMed1993

Synaptic organization and prefrontal corticothalamic termination in the mediodorsal thalamic nucleus of the cat.

The synaptic organization of the mediodorsal thalamic nucleus (MD) in the cat have been studied with the electron microscope, and correlated with the termination of the medial prefrontal corticothalamic afferents using the method of anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). The neuropil of MD was divided into glomerular and extraglomerular regions. A synaptic glomerulus was composed of a central dendrite and some different presynaptic profiles with astroglial ensheathment. The prevalent presynaptic elements in glomeruli were presynaptic dendrites (PSDs) that contained pleomorphic vesicles, and formed symmetric synaptic contacts and puncta adhaerentia junctions with central dendrites. One or two large terminals with round vesicles and asymmetric specializations (LR) also participated in glomerular formations. They were invariably presynaptic to central dendrites and PSDs. As terminals less frequently found within glomeruli, there were small-sized terminals with round vesicles and asymmetric synaptic junctions with PSDs. In the extraglomerular neurophils, small to medium-sized terminals with pleomorphic vesicles (SMP) were found besides the presynaptic profiles identified in glomerular regions. These SMP terminals formed axodendritic and axosomatic symmetric synapses. WGA-HRP injections into the medial prefrontal cortex resulted in anterograde labelings in not only SR but also LR presynaptic terminals. SR boutons made up the majority of labeled terminals, and they were found only in the extraglomerular neuropil. While labeled LR terminals were detected in the extraglomerular neuropil and synaptic glomeruli with less encounter. The results of the present study show that the synaptic organization in MD of the cat is similar to that in other thalamic relay nuclei and in MD of the monkey. Further, MD receiving two subsets of synaptic terminations from the prefrontal cortex might play a different functional role in regulating the neural circuit between MD and the prefrontal cortex in comparison with that in the sensory and motor thalamic nuclei that receive only SR terminals from the sensorimotor cortex.

Animals↗