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Biomedical subjects

S Konishi

Publications and source records attributed to S Konishi.

At least 91 records · Page 5Linked to original sources
PubMed1993

Involvement of NK1 receptors in synaptic transmission in the guinea pig coeliac ganglion.

Using intracellular recording techniques, we examined the effects of tachykinin receptor agonists and antagonists on electrophysiologically identified tonic neurons of the isolated guinea pig coeliac ganglion. In most of the tonic neurons, substance P (SP), neurokinin A (NKA) and/or senktide induced a depolarization. The effects of SP and NKA were blocked by the NK1-selective antagonist, GR71251 (5 microM), but not by the NK2-selective antagonist, L659,877 (10 microM), whereas the effect of senktide was not affected by these antagonists. The NK1-selective agonists, [Sar9,Met(O)2(11)]SP and SP methyl ester, and the NK3-selective agonist, [MePhe7]neurokinin B, also evoked depolarizations in tonic neurons. By contrast, the NK2-selective agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, at 1 microM each, did not evoke any significant depolarizing response. Repetitive electrical stimulation of the mesenteric nerves induced slow excitatory postsynaptic potentials (EPSPs) in the majority of tonic neurons, which were depressed by GR71251 (5 microM). These results suggest that NK1 and NK3 receptors but not NK2 receptors are involved in the tachykinin-induced depolarization of tonic neurons, and that the NKA-induced response is due to the activation of NK1 receptors. This study also suggests the involvement of NK1 receptors in the slow EPSPs in tonic neurons.

Animals↗
PubMed1993

Studies on secular changes in the concentration of lead accumulated in organs and rib of Japanese.

As environmental pollution due to waste fluids and gases from factories using lead (Pb), as well as domestic waste materials, has become a matter for public concern, studies on the accumulated levels of Pb in man have become necessary for defining the degree of contamination in the ordinary population. For this purpose, Pb levels in tissues of 76 forensic cadavers were determined in order to investigate the age distribution of accumulated Pb, and 120 samples were used to clarify secular changes in Pb accumulation during the last decade in the general population. The age group showing the highest Pb level was 50-59 years, with mean Pb contents per unit wet weight of 0.262, 0.520, 0.427 and 4.479 micrograms/g for heart, liver, kidney and rib, respectively. Each of these organs in all age groups exhibited almost the same Pb levels, but babies less than one year old had levels close to those in adults. However, ribs in babies exhibited much lower Pb levels. The levels in each organ were lower in individuals over 60 years old. A distinct age-related increase in Pb levels was found only in ribs from age 0 year to 50-59 years. The Pb levels in the heart, liver, kidney and rib showed a decrease during the last 10 years from 0.188 +/- 0.073 to 0.006 +/- 0.003 micrograms/g, from 0.307 +/- 0.169 to 0.076 +/- 0.057 micrograms/g, from 0.287 +/- 0.145 to 0.021 +/- 0.011 micrograms/g and from 3.203 +/- 1.477 to 2.366 +/- 1.469 micrograms/g, respectively.

Adolescent↗
PubMed1993

[Study on secular changes of cadmium concentration accumulated in main organs of Japanese].

With the development of the mining and manufacturing industries and the petrochemical industry, cadmium (Cd) has been used not only for metal products but also petroleum products. Recently, environmental pollution due to waste fluids and gases from factories using cadmium and also domestic waste materials has become a cause for concern. In this connection, studies on the accumulated levels of Cd in the human body, its age-distribution in the general population and its secular changes during the last decade would be useful for clarifying the degree of contamination in the human body and providing an index which could be used as a basis for preventive measures against environmental pollution. For this purpose, the levels of Cd accumulated in main organs of the human body were determined using forensic data 3 times at 5-year intervals starting in 1976. The age intervals starting in 1976. The age group having the highest Cd level was 50-59 years, old and the mean weights of Cd per wet weight of heart, liver and kidney were 0.421, 2,984 and 56.43 micrograms/g, respectively. Each of these organs in babies less than a year old exhibited lower Cd levels, but teenagers had levels close to those in adult. However, the level in each organ was lower in individuals over 60 years old. 4 distinct age-related increase in the level of Cd was found only in the kidney. The levels of accumulated Cd in the liver and kidney showed a rise during the last 10 years from 2.358 to 5.568 micrograms/g and from 43.95 to 73.47 micrograms/g, respectively, whereas the Cd level in the heart has remained about the same, i.e. from 0.207 to 0.181 micrograms/g.

Adolescent↗
PubMed1992

An after-depolarization following action potentials and its modulation by substance P in rat sympathetic neurons.

Sympathetic neurons in rat coeliac-superior mesenteric ganglia (C-SMG) displayed an after-depolarization (ADP) following action potentials and after-hyperpolarization. The ADP had amplitudes of 3-10 mV and lasted for 2-6 s, during which membrane resistance and excitability of C-SMG neurons increased. The reversal potential of ADP was dependent on external K+ concentrations. The ADP was suppressed in a solution containing Cd2+ or zero Ca2+. The ADP thus appears to be produced by inhibition of certain K+ channels via a Ca(2+)-dependent process. Substances P (SP) depolarized ganglion cells and increased the ADP, leading to a long-lasting increase in membrane excitability of rat C-SMG neurons.

Action Potentials↗
PubMed1992

Fast and slow depolarizations produced by substance P and other tachykinins in sympathetic neurons of rat prevertebral ganglia.

Using intracellular recording, we examined the effects of three mammalian tachykinins, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), on sympathetic neurons of isolated rat coeliac-superior mesenteric ganglia (C-SMG). The 3 tachykinins elicited two distinct depolarizing responses in ganglion cells: fast depolarization with time-to-peak of 1-2 sec and duration of 5-10 sec, and slow depolarization with time-to-peak of about 20 sec and duration of 120-140 sec. Both fast and slow responses persisted in a solution containing low Ca2+ and high Mg2+ or tetrodotoxin, which indicates that the tachykinins directly act on ganglion cells to produce fast and slow depolarizations. The two types of tachykinin-induced responses exhibited clearly distinguishable properties. The membrane conductance was increased during the fast response, but not significantly changed, slightly decreased or sometimes increased during the slow response. Within certain range of membrane potential, the amplitude of fast response increased upon membrane hyperpolarization and decreased upon depolarization of ganglion cells. In contrast, the amplitude of slow response associated with membrane conductance decrease was increased with membrane depolarization and decreased with hyperpolarization. The fast response was markedly suppressed in a Na(+)-deficient solution, a solution containing nominally zero Ca2+ (plus 0.1 mM EGTA in some cases), and in a solution containing Cd2+ or Mn2+, whereas the slow response was not affected in these solutions and was augmented in some cells in K(+)-free solution. Thus it seems that the increase in Ca(2+)-dependent cationic conductance underlies the fast response and that the slow response is produced at least in part by suppression of certain K+ channels. The fast response progressively decreased in amplitude upon repeated application of the peptides with short intervals, whereas the slow response was rather augmented by repeated application. Lowering the temperature markedly depressed the slow response, while the fast response remained almost unaffected. It is therefore likely that the fast and slow depolarizations are mediated by two different subtypes of tachykinin receptors or a single class of receptors linked with two different intracellular mechanisms. Measurement of tachykinins in several sympathetic ganglia by combined use of HPLC and radioimmunoassay revealed that the highest amount of SP occurs in the C-SMG where the content of SP (136.0 pmol/g protein) was higher than those of NKA (44.3) and NKB (18.7). SP thus appears to function as a major tachykinin in rat C-SMG.

Animals↗
PubMed1991

Adrenergic and cholinergic inhibition of Ca2+ channels mediated by different GTP-binding proteins in rat sympathetic neurones.

Effects of acetylcholine (ACh) and noradrenaline (NA) on voltage-gated ion channels of sympathetic neurones acutely dissociated from rat superior cervical ganglion (SCG) were examined using the whole-cell voltage-clamp technique. Depolarizing voltage steps elicited two types of low- and high-voltage-activated (LVA and HVA) Ca2+ currents. Pressure applications of ACh and NA produced concentration-dependent inhibition of the HVA Ca2+ current without affecting the LVA Ca2+ current. The inhibitory action of ACh on the Ca2+ current was blocked by a muscarinic antagonist, atropine. The action of NA was suppressed by an alpha 2-adrenergic antagonist, yohimbine, but not by an alpha 1-adrenergic antagonist, prazosin. Delayed rectifying outward K+ currents and inward rectifying K+ current were not affected by either ACh or NA. Tetrodotoxin-sensitive and -insensitive Na+ currents also remained unaffected under actions of ACh and NA. When recorded with electrode containing guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), the inhibitory actions of ACh and NA on Ca2+ currents became irreversible. After treatment of SCG neurones with pertussis toxin, the inhibitory action of ACh on the Ca2+ current was almost completely abolished, whereas the action of NA was only partially reduced. The results suggest that ACh and NA differentially inhibit the HVA Ca2+ current via different G proteins coupling muscarinic and alpha 2-adrenergic receptors to Ca2+ channels in rat SCG neurones.

Acetylcholine↗
PubMed1991

Enzyme-linked immunosorbent assay for the detection of canine coronavirus and its antibody in dogs.

Two methods of enzyme-linked immunosorbent assay (ELISA) were developed for the diagnosis of canine coronavirus (CCV) infection in dogs. One ELISA, in which CCV-infected CRFK cell lysate is used as antigen, is for the detection and titration of antibody against CCV, and the other ELISA uses the double antibody sandwich method for the detection of CCV antigen. The first ELISA procedure demonstrated antibody responses in dogs inoculated with CCV, as did the virus neutralization test; the second ELISA detected specific CCV antigen in feces and organ homogenates of inoculated dogs.

Animals↗
PubMed1991

Effects of biological response modifiers on childhood ALL being in remission after chemotherapy.

Of 125 children with acute lymphoblastic leukemia (ALL), who had been in continuous remission for three years on chemotherapy, 108 patients received biological response modifiers (BRM) such as Bestatin, N-CWS, OK-432 and/or PSK in order to prevent relapse after treatment suspension. From 20 patients who were treated with PSK, 6 relapsed within 13 months. This relapse rate was quite similar to the rate observed with those children who were off therapy (4 relapses in 17 patients within 13 months). In contrast to these 37 patients, only 3 out of 31 patients who received Bestatin (p less than 0.05) and 8 out of 57 patients who received N-CWS or OK-432 relapsed. Based on these findings, BRMs used in the present study seems to be effective to prevent relapse of leukemia among childhood ALL who have electively stopped chemotherapy.

Antibiotics, Antineoplastic↗
PubMed1991

[Receptor mechanisms underlying the actions of substance P and related neuropeptides].

The excitability of peripheral and central neurons is regulated by two types of ion channels, voltage- and ligand-operated ones. Recent studies have revealed that the activities of these ion channels are under the control of a variety of classical neurotransmitters and neuropeptides. In particular, certain ion channels such as voltage-dependent Ca and K channels are reciprocally regulated by excitatory and inhibitory neurotransmitters, leading to the excitation and inhibition of nerve cells: for example, 1) the activation of voltage-dependent K channel is facilitated by somatostatin and inhibited by substance P, and 2) the opening of voltage-gated Ca channel is augmented by substance P and suppressed by somatostatin and certain opioid peptides. The ligand-gated ion channel, nicotinic acetylcholine receptor is also controlled by the actions of neuropeptides, substance P and calcitonin gene related peptide (CGRP). The regulation of ion channels with neuropeptides may contribute not only to the control of neuronal excitability but also to the plasticity of the nervous system.

Animals↗
PubMed1991

[Requirements of diagnostic criteria for aplastic anemia in children].

As a general rule, diagnostic criteria of aplastic anemia in children are the same as adult criteria. However, blood counts of normal children show wide age-related variation, therefore we must establish a system of adjustment for diagnosis of aplastic anemia in children. The data of children with aplastic anemia visiting our institutes from 1966 to 1990 were evaluated for this study. RBC below 350 x 10(4)/microliters, WBC below 4,000/microliters or neutrophils below 1,500/microliters, platelets below 8 x 10(4)/microliters, reticulocytes below 4 x 10(4)/microliters and lymphocytes over 60% were seemed to satisfy the diagnostic criteria of aplastic anemia proposed by the Study Group of hemopoietic Disorders sponsored by the Ministry of Health and Welfare of Japan. Fifteen children (4.6%) did not meet these criteria and as such were diagnosed as atypical aplastic anemia. Thirteen of them were in a pre-aplastic state and developed typical aplastic anemia within 6 months to 8 years after the initial diagnosis. Clinical findings of these patients showed the decrease in number of megakaryocytes and committed stem cells in bone marrow. Three of these patients developed acute non-lymphocytic leukemia, and 2 of them were diagnosed as Fanconi's anemias.

Adolescent↗
PubMed1990

Down's syndrome and acute leukemia in children: an analysis of phenotype by use of monoclonal antibodies and electron microscopic platelet peroxidase reaction.

The clinical, hematologic, and immunophenotypic features in 20 patients with Down's syndrome (DS) and acute leukemia were analyzed. Of the 20 patients, all 14 patients who were 3 years old and less were diagnosed as having acute megakaryoblastic leukemia (AMKL) by use of platelet-specific monoclonal antibodies and platelet peroxidase (PPO) reaction in electron microscopy. They were characterized by the presence of bone marrow fibrosis, having a history of myelodysplastic syndrome (MDS) and a poor response to chemotherapy. Only one patient has remained in continuous complete remission for more than 1 year. Acute leukemia in six patients who were older than 4 years was classified as common acute lymphoblastic leukemia antigen (CALLA)-positive acute lymphoblastic leukemia (ALL). In one of six patients classified as ALL, the leukemic blasts simultaneously expressed myeloid-associated surface antigens. All six patients achieved a complete remission and have remained in continuous complete remission and have remained in continuous complete remission from 10 to 52 months from the initial diagnosis. Although it has been suggested that the distribution of types of acute leukemia in patients with DS is similar to that in normal children, the present study shows that the distribution of acute leukemia types is quite different from that in patients without Down's syndrome.

Antibodies, Monoclonal↗
PubMed1990

Effects of sulfur-containing metabolites of hexachlorobenzene on the heme metabolic enzymes in rat liver.

Effects of hexachlorobenzene (HCB) and its sulfur-containing metabolites on the heme metabolic enzymes in rat liver were investigated. A single injection of HCB caused the increase in activities of delta-aminolevulinic acid (ALA) synthetase and heme oxygenase, and contents of cytochrome P-450 and total heme. After a single injection of pentachlorothioanisol (PCTA) or pentachlorophenyl methyl sulfore (PCPSO2Me), ALA synthetase activity was enhanced. Heme oxygenase activity was increased by PCPSO2Me treatment. Cytochrome P-450 and total heme contents were increased by PCPSO2Me or 1,4-bis(methylthio)tetrachlorobenzene (MTTCB). When HCB was injected once daily for 5 weeks, a marked increase in ALA synthetase activity, a significant decrease in ALA dehydratase, almost complete inhibition of uroporphyrinogen decarboxylase activity, and an increased excretion of total porphyrin in the urine were shown. After chronic treatment with its sulfur-containing compounds, PCPSO2Me and MTTCB produced a significant increase in ALA synthetase activity. However, activities of ALA dehydratase and uroporphyrinogen decarboxylase, and excretion of total porphyrin in the urine were unaltered. At this time, the concentrations of the corresponding sulfur-containing compound and related metabolite(s) in blood, liver and kidney were nearly the same as those observed in HCB-treated rats. It is suggested that PCPSO2Me and MTTCB could induce the hepatic ALA synthetase, but, these metabolites, and also PCTA, were not able to induce the porphyria in female rats, and the induction of porphyria by HCB is not attributable to the action of its sulfur-containing compound.

5-Aminolevulinate Synthetase↗
PubMed1990

Serotypes and antimicrobial susceptibility of Pseudomonas aeruginosa strains isolated from diseased dogs.

Strains of Pseudomonas aeruginosa isolated from diseased dogs in Tokyo area during 1983 through 1986 were serotyped and assayed for antimicrobial susceptibility to obtain an epizootiological aspect of canine P. aeruginosa infection. Major sources of specimens were ear and nasal discharges and urine. The results of O-antigen typing using a monoclonal antibody kit showed that the most predominant serotype was type M. Types G and B were also major serotypes. In a yearly distribution of serotypes, type I was almost limited in 1986, and was isolated mainly from surgical wounds, which showed an episode of nosocomial infection, whereas that of type M or B was dispersed during 4 years from 1983 to 1986. As a result of antimicrobial susceptibility test, most canine strains were considered to be susceptible to 4 drugs, which were commonly used in both human and veterinary clinics, in contrast to human isolates.

Animals↗
PubMed1990

[Legionellosis].

Although increasing attention is being given to Legionella pneumonia in Japan, reports of solitary onset of this disease are scant in Japan. The patient, from whom L. dumoffii was isolated, was a 59-year-old male with no underlying disease. He visited our hospital because of fever and cough, and was admitted to our department for X-ray findings consistent with pneumonia. After admission, pulmonary lesions spread rapidly, and based on the suspicion of Legionella pneumonia, drugs such as EM, RFP and MINO were used. However, the patient died on the 26th hospital day. L. dumoffii was isolated from specimens obtained by airway aspiration before death and specimens of lung abscess and airway discharge obtained during autopsy (7 specimens in total). In addition, the L. dumoffii antibody titer in the serum became elevated. This is the first case of L. dumoffii pneumonia reported in Japan. The other case was in an 81-year-old male with underlying disease. He was admitted urgently with suspected pneumonia but died on the following day. L. pneumophila serogroup 5 was isolated from autopsied lung tissue. Fatality is high for this disease, making early diagnosis and treatment with appropriate antibiotics essential. Physicians should bear in mind the possibility of this disease and request the necessary laboratory tests in suspected cases without delay.

Aged↗
PubMed1990

[Clinical study of imipenem/cilastatin sodium in children with severe infections].

Clinical studies of imipenem/cilastatin sodium (IPM/CS) were conducted in 40 pediatric patients. 29 out of the 40 patients were treated for infections and 11 for prophylaxis. The following results were obtained. 1. The response rate in 29 patients with infections was 79.3%. Among the 29 patients, 16 patients who presented with malignant diseases showed the response rate of 68.8%. The response rate was lower in patients with severe infections than in those with mild or moderate infections, and a lower response rate was associated with severe neutropenia. However, there were no differences in the response rates between patients who had previously been treated and those who had been untreated with other antibiotics. The response rate in 6 patients from whom causative organisms were isolated was 83.3% and that in the remaining 23 patients was 78.3%. 2. The response rate in 11 patients to whom IPM/CS was administered prophylactically was 63.6%. 3. As for side effects, a rash was observed in 1 patient and hematuria in another, and the abnormal laboratory test results observed were elevations of GOT and GPT in 1 patient. However, they were not clinically significant. From the above results, it appears that IPM/CS may be used as a drug of the first choice for the treatment of patients with severe infections in which the causative organisms are unknown, and for the prophylaxis of infection in patients with neutropenia.

Bacterial Infections↗
PubMed1989

Different GTP-binding proteins mediate regulation of calcium channels by acetylcholine and noradrenaline in rat sympathetic neurons.

In dissociated neurons of rat superior cervical ganglion (SCG), noradrenaline (NA) and acetylcholine (ACh) suppressed Ca2+ currents elicited by depolarizations to 0 mV from -60 mV. With GTP-gamma-S in patch electrodes, ACh and NA caused persistent inhibition of Ca2+ currents. Pretreatment of SCG cells with pertussis toxin abolished the action of ACh but not of NA. The results suggest that ACh and NA reduce the Ca2+ currents in SCG cells through different G proteins.

Acetylcholine↗
PubMed1989

Tachykinins produce fast and slow depolarizations in sympathetic neurons of rat coeliac-superior mesenteric ganglia.

The actions of mammalian tachykinins on neurons of rat coeliac-superior mesenteric ganglia (C-SMG) were examined using intracellular recording in isolated preparations. Application of substance P, neurokinin A and neurokinin B produced fast and slow depolarizations in the ganglion cells. The two responses were clearly distinguishable in their electrophysiological characteristics. The results suggest that different receptor mechanisms are involved in fast and slow depolarizing actions of tachykinins in rat C-SMG cells.

Animals↗