Biomedical subjects

S Sawada

Publications and source records attributed to S Sawada.

At least 217 records · Page 12Linked to original sources

PubMed1994

Analysis of mitotic cell death caused by radiation in mouse leukaemia L5178Y cells: apoptosis is the ultimate form of cell death following mitotic failure.

The appearance of various abnormal cells after irradiation was investigated in growing mouse leukaemia L5178Y cells. Morphologically defined apoptotic cells started to emerge at 10 h after irradiation and the frequency reached a peak at around 48 h being similar to the frequency of other abnormal cells, i.e. micronucleated, multinucleated and giant cells. Necrotic cells were rarely seen. The frequency of apoptosis and other abnormal cells depended on the radiation dose. The typical DNA ladder pattern for apoptosis was observed in the agarose gel electrophoretic analysis of the cells at 24-96 h postirradiation. A decline in the frequency of apoptotic cells occurred with longer incubation, which was associated with a sharp increase in cloning efficiency. Changes in the growth rate of the irradiated cell population during the postirradiation period could be reasonably well described by a simple model using the frequencies of apoptosis and other abnormal cells. The results suggest that apoptosis is the ultimate form of cell death via mitotic failure caused by relatively small doses of radiation in L5178Y cells.

3T3 Cells↗

PubMed1994

Effects of 252Cf neutrons, transmitted through an iron block on human lymphocyte chromosome.

Chromosome aberration of human peripheral blood lymphocytes exposed to californium-252 (252Cf) neutrons transmitted through a 15 cm thick iron block was analysed. The spectrum of the filtered neutrons ranged from 0.1 to 2 MeV with a peak at 0.7 MeV, simulating the Hiroshima atomic bomb neutron spectrum as shown in the Dosimetry System 1986 (DS86). Chromosome aberration frequencies after exposure to filtered and unfiltered 252Cf radiation were compared. Acentric ring chromosomes were significantly increased (p < 0.05) in the filtered condition. However, yields of dicentrics and centric rings induced by the filtered neutrons were not statistically different from those induced by the unfiltered neutrons (p > 0.1). The relative biological effectiveness (RBE) of the neutrons with respect to the formation of dicentrics and centric rings was 10.9 and 12.3 in the filtered and unfiltered conditions respectively, but the difference was not statistically significant. These results provide useful information for the re-evaluation of the biological effect of the Hiroshima atomic bomb radiations.

Californium↗

PubMed1994

Cumulative effects of chromosome aberrations and sister chromatid exchanges in rat liver induced in vivo by heterocyclic amines.

Cumulative effects of chromosome aberrations and sister chromatid exchanges (SCEs) were studied in hepatocytes of F344 rats exposed in vivo to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) at doses of 12.5, 25 or 50 mg/kg body wt/day or 2-nitro-3-methylimidazo[4,5-f]quinoline (nitro-IQ) at doses of 12.5, 25 or 50 mg/kg body wt/day. Hepatocytes were isolated 24 h after 1, 7, 14 or 28 repeated doses (once a day) by gastric intubation and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor. Cells were fixed after a culture period of 48 h. Multiple treatment with IQ or nitro-IQ induced significant chromosome aberrations time- and dose-dependently, the maximum frequency of chromosome aberrations in metaphase cells being 39 and 33% respectively, while that in controls was 1.1%. Single treatment with IQ or nitro-IQ induced significant SCEs dose-dependently, the maximum frequency being 0.83 and 0.79 per chromosome respectively, while the control value was 0.51. Multiple treatment with nitro-IQ induced significant SCEs to a plateau level of 0.90 per chromosome. Cytogenetic damage in the liver by IQ was greater than that by nitro-IQ. These results show that this assay of chromosome aberrations and SCEs in rat liver in vivo without partial hepatectomy or mitogen treatment in vivo is a sensitive method for evaluating the cumulative tumor-initiating activities of carcinogenic heterocyclic amines at low doses and should be useful for the detection of unknown hepatocarcinogens.

Amines↗

PubMed1994

Molecular genetic analysis of the von Recklinghausen neurofibromatosis (NF1) gene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method.

Von Recklinghausen neurofibromatosis (NF1) is a common autosomal dominant disorder characterized by abnormalities in multiple tissues derived from the embryonic neural crest. The NF1 gene has been mapped to the pericentromeric region of the long arm of chromosome 17. Chromosome walking and sequencing of the NF1 gene have extended it's open reading frame; to date 49 exons have been identified. To investigate the mutation of the NF1 gene, the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method was applied to 4 exons of NF1 genes. We examined the DNAs from 49 samples, including those of 23 Japanese patients with NF1 (4 of these patients developed malignant schwannoma), a patient with segmental neurofibromatosis, and 14 clinically normal controls. A mutational band was detected in an exon of a tumor DNA extracted from a malignant schwannoma of a female NF1 patient. However, the mutation was not found in the germ line DNA of this patient. No mutations were detected in the other samples.

Adolescent↗

PubMed1994

Suicide in patients with systemic lupus erythematosus: a clinical analysis of seven suicidal patients.

Despite many suicidal cases in patients with systemic lupus erythematosus (SLE), literature on this subject is lacking. To elucidate and prevent this phenomenon, we re-evaluated the clinical records of seven suicidal patients with SLE. Six patients had photosensitivity and insomnia. At the time of the suicide attempt, hypocomplementemia was observed in five of six patients. Diffuse slowing on electroencephalograms were observed in four of five patients. One patient successfully committed suicide while on no therapy while five patients made their attempts under the tapering courses of steroids. Five patients manifested psychoses whereas two patients displayed no psychotic findings. All patients attempted suicide shortly after admission (mean time 20 days). The subsequent courses of the survivors who received more medication were favorable. Therefore, it appears that disease activity was not fully controlled in these patients. Furthermore, signs of an imminent suicide attempt were missed in some cases. Psychosis, insomnia, history of photosensitivity, an incompletely controlled disease state, receiving tapering steroid dose, diffuse slowings on electroencephalograms and the presence of hypocomplementemia appeared to be risks for attempting suicide in SLE. We would recommend that such patients be under psychiatric care for at least 2 months to prevent suicide. When the patient is still psychotic or unstable, further medical care will be required.

Adolescent↗

PubMed1994

Synthesis and antitumor activity of 20(S)-camptothecin derivatives. A-ring-substituted 7-ethylcamptothecins and their E-ring-modified water-soluble derivatives.

Twenty-six novel A-ring-modified 7-ethylcamptothecins (6) were synthesized by Friedländer's condensation of the chiral tricyclic ketone (5) with aminopropiophenones (4). The compounds substituted with fluorine at the 11 position showed strong cytotoxicity to KB and L1210 cells. The 11-fluoro derivatives also exhibited strong inhibitory activity on DNA topoisomerase I. Nine compounds 6 with four to ten times stronger cytotoxicity than that of camptothecin were selected and converted into water-soluble 17-O-acyl amide derivatives (8). Compounds 8e (10-Me, O-COCH2CH2SCH3) and 8f (11-F, O-COC2H5) showed activity towards Meth A in mice that was comparable to that of CPT-11, at lower doses than CPT-11.

Animals↗

PubMed1994

Crow-Fukase syndrome: a case associated with vasospastic angina.

The patient is a 60-year-old man who developed numbness of the extremities, paralysis, hyperpigmentation of the skin, hypertrichosis, anasarca and chest pain at the age of 58 years. The diagnosis of Crow-Fukase syndrome was made and myeloma was not found. Prednisolone therapy was effective but chest pain reappeared every morning when prednisolone was tapered to 30 mg alternate day. Coronary arteriogram showed no stenosis but administration of acetylcholine into the coronary artery produced ST elevation in electrocardiogram, chest pain and coronary artery stenosis which were relieved by administration of nitrates into the coronary artery.

Acetylcholine↗

PubMed1994

Protein C deficiency found in a patient with acute myocardial infarction: a single base mutation 157 Arg (CGA) to stop codon (TGA).

Protein C has an important role in the regulatory mechanisms of coagulation and fibrinolysis. In patients with heterozygous protein C deficiency, there is an increased risk for thromboembolic disease, especially in the venous system. We describe a patient with protein C deficiency presenting with an acute myocardial infarction (AMI). Direct sequence analysis of the whole protein C gene detected a single base mutation at exon 7; 157 [Arg(CGA) to stop codon (TGA): 6182 C to T]. Thus, the patient was suspected to have a deficiency of the protein C heavy chain molecule, resulting in both a low protein C antigen and activity level. The mutation was also found in the propositus' son and was confirmed by differential termination of the primer extension (DTPE).

Base Sequence↗

PubMed1994

Intraarterial occlusion by radiofrequency.

Arterial occlusion using radiofrequency energy was performed. The length of the noninsulated part of the guidewire was 10 mm and the duration of radiofrequency supply was 20 s. Animal experiments were carried out in 17 canine arteries; 4 out of 6 arteries less than 2.3 mm in diameter were completely occluded during the 20 s radiofrequency supply. A clinical application was also successfully performed without any complications. Arterial occlusion with radiofrequency can be applied to vessels less than about 2 mm in diameter.

Animals↗

PubMed1994

Significant increases in serum CA125 and CA19-9 following torsion from an adenofibroma of the ovary: a case report.

Significant increases in the serum levels of cancer antigen 125 (CA125) and carbohydrate antigen 19-9 (CA19-9) were observed over one month prior to the removal of an ovarian adenofibroma. The serum levels of CA125 and CA19-9 decreased rapidly after surgery. The surface of the tumor at surgery showed marked inflammation, probably induced by the necrosis produced by torsion. Pathologically, most of the tumor was necrotic, and histoimmunochemical staining of the viable cells was weak for CA125 but intense for CA19-9. Clinicopathological observations of the case suggested that CA125 and CA19-9 might be stimulated in the cells by inflammation or that originally existing CA125 and CA19-9 were released from the tumor cells following the cell necrosis.

Adenofibroma↗

PubMed1993

CD4 function in thymocyte differentiation and T cell activation.

The ectodomains of the T cell surface glycoproteins CD4 and CD8 bind to membrane-proximal domains of MHC class II and class I molecules, respectively, while both cytoplasmic domains interact with the protein tyrosine kinase (PTK) p56lck (lck) through a shared cysteine-containing motif. Function of CD4 and CD8 requires their binding to the same MHC molecule as that recognized by the T cell antigen receptor (TCR). In vitro studies indicate that CD4-associated lck functions even in the absence of kinase activity. In vivo experiments show that, whereas helper T cell development is impaired in CD4-deficient mice, high level expression of a transgenic CD4 that cannot bind lck rescues development of this T cell subset. These studies suggest that CD4 is an adhesion molecule whose localization is regulated through protein-protein interactions of the associated PTK and whose function is to increase the stability of the TCR signalling complex by binding to the relevant MHC. The function of CD4 in development has been further studied in the context of how double positive (CD4+CD8+) thymocytes mature into either CD4+ T cells with helper function and TCR specificity for class II or into CD8+ T cells with cytotoxic function and specificity for class I. Studies using CD4-transgenic mice indicate that development of single positive T cells involves stochastic downregulation of either CD4 or CD8, coupled to activation of a cytotoxic or helper program, respectively, and subsequent selection based on the ability of the TCR and remaining co-receptor to engage the same MHC molecule.

Animals↗

PubMed1993

ATP-sensitive K+ channel activators suppress the GABAergic inhibitory transmission by acting on both presynaptic and postsynaptic sites in rat cultured hippocampal neurons.

Effects of ATP-sensitive K+ (KATP) channel activators on the inhibitory transmission were explored by applying the patch-clamp technique to both presynaptic and postsynaptic hippocampal neurons prepared from neonatal rats. Diazoxide (0.5 mM) and cromakalim (0.5 mM) reduced GABAergic synaptic currents to 57 and 81% of control, respectively, and reduced the currents induced by exogenously applied GABA (10 microM) to 74 and 95% of control, respectively. These results suggest that KATP channel activators suppress the GABAergic transmission partly by reducing the GABA release and partly by affecting the postsynaptic GABA response.

Action Potentials↗

PubMed1993

[Experimental study with radiofrequency-induced thermal arterial occlusion].

A preliminary experiment on arterial occlusion using radiofrequency energy was performed. A surgitron FFPF was used as a radiofrequency power generator, and a Tracker 18 catheter was used as a probe insulator. A 10 mm length of the guide wire protruding from the tip of catheter was used as the radiofrequency probe. To examine the safety of this procedure within the vessels, the following experiments were performed. A 2.5 mm diameter dimple at the surface of a sausage was filled with human blood. We inserted various lengths of non-insulated guide wire into the dimple and supplied radiofrequency power. We then measured the time until air bubbles appeared in the dimple. With a 10 mm length of non-insulated guide wire, this took over 30 sec. Animal experiments were carried out in 17 canine arteries. The diameter of these arteries ranged from 1.3 to 3.7 mm. Before the procedure, angiograms were taken using a 5 F catheter from the right femoral artery. A tracker 18 catheter and guide wire were inserted to the target position co-axially. The guide wire was attached to the radiofrequency generator. The tip of the guide wire functioned as the convergence point of an electrically conducting induced current. Treatment was performed by supplying radiofrequency power of various durations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Electrophysiological features of habenular neurons of the guinea pig: high efficacy of synaptic transmission and variable configuration of unitary spikes.

Properties of single cell discharges recorded extracellularly in the medial habenular nucleus (MHN) were examined in guinea pig MHN slices. MHN neurons fired spontaneously as well as in response to stimulation of the stria medullaris. Positive deflections representing excitatory postsynaptic potentials (EPSPs) were recorded in isolation from a neuron. In most neurons, however, EPSPs differentiable from the base-line triggered action potentials consistently, and were recorded in isolation only during administration of 6-cyano-7-nitroquinoxaline-2.3-dione. Increases in spontaneous discharge rate during administration of nicotinic agonists were not accompanied by expected decreases in latency of synaptically-evoked spikes. Action potentials were recorded as biphasic potential changes consisting of a smaller positive phase and a subsequent negative phase. The amplitude of the negative phase in synaptically-evoked spikes fluctuated from trace to trace and was larger than in spontaneous spikes. The above observations suggest high efficacy of synaptic transmission from the stria medullaris to MHN neurons and variable areas of the soma-dentritic region invaded by action potentials generated in the initial segment.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1993

Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjögren's syndrome.

To better define the genetic factors that predispose to primary Sjögren's syndrome (SS), we have used polymerase chain reaction in combination with oligonucleotide probe hybridization and DNA sequencing to analyze HLA-DRB1, -DQA1, -DQB1, and -DPB1 alleles in Caucasoid (California), Japanese (Tokyo), and Chinese (Shanghai and Beijing) SS patients. In comparison to local controls in each region, we found: 1) increased frequency of the predicted haplotype HLA-DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201 in Caucasoid patients (p < 0.001); 2) increased frequency of the predicted haplotype HLA-DRB1*0405-DRB4*0101-DQA1*0301-DQB1*0401 in Japanese patients (p < 0.05); 3) increased frequency of the predicted haplotype DRB1*0803-DQA1*0103-DQB1*0601 in Chinese patients (p < 0.05); and 4) no statistically significant association with DPB1 alleles in any group, although an increased number of Caucasoid and Japanese SS patients possessed DPB1*0301. Comparison of DNA sequences for the three disease-associated haplotypes in these ethnic groups revealed a shared region of predicted amino acids from positions 58 to 69 in the first domain of HLA-DQB1. These results extend previous studies by demonstrating that no single class II allele was associated with 1 degree SS in the different ethnic groups. However, a shared amino acid motif in the DQB1 first domain was present in each disease-associated haplotype.

Alleles↗

PubMed1993

[A study of transsplenic CO2 gas enhanced portal angioechography].

Transsplenic CO2 gas enhanced portal angioechography was examined. The spleen of three dogs was punctured by 23 gauge needle with two side holes. From 5 ml to 20 ml of CO2 gas was injected into the splenic vein via the splenic parenchyma, and elevation of echo level of the liver was observed. Hematoma was not seen at the site of puncture. Good image was obtained in the case of 5 ml CO2 injection. In one dog with pseudotumor in the liver, the hyperechoic tumor changed into negative enhanced nodule after CO2 gas enhancement. Transsplenic CO2 gas enhanced portal angioechography is thought to be useful to evaluate hepatic tumors.

Animals↗

PubMed1993

Quantal analysis of modulating action of adenosine on the mossy fiber synapse in hippocampal slices.

Although adenosine has been considered to depress release of neurotransmitter in central synapses, evidence for this notion is circumstantial. To obtain more direct and quantitative evidence, the suppressing action of adenosine on transmission through the mossy fiber synapse was examined by a quantal analysis in thin transverse sections of the guinea pig hippocampus. Adenosine suppressed excitatory postsynaptic potentials (EPSPs) induced in CA3 neurons by activation of single mossy fibers to 57 +/- 19% at 10 microM (6 neurons). The input resistance of the postsynaptic neurons was reduced to 84 +/- 5%. The suppression of the unitary EPSPs was accompanied by a reduction of the mean quantal content (m) to 51 +/- 13% with no significant decrease in mean quantal amplitude (q). These findings indicate that adenosine at 10 microM suppresses transmission through mossy fiber synapses mainly by depressing release of transmitter. This study provides direct evidence for the presynaptic action of adenosine on central synapses for the first time.

Action Potentials↗

PubMed1993

Regulated expression of human CD4 rescues helper T cell development in mice lacking expression of endogenous CD4.

During T cell development, precursor thymocytes that co-express the CD4 and CD8 glycoproteins give rise to mature progeny expressing one of these molecules to the exclusion of the other. Continued expression of only CD4 is the hallmark of mature helper T cells, whereas cytotoxic T cells express CD8 and extinguish CD4. The differentiation program that generates the two T cell subsets is likely to be intimately tied to regulation of expression of these cell surface molecules. We now describe the use of a murine CD4 enhancer in the generation of transgenic mice expressing physiologic levels of human CD4. The transgene is appropriately regulated during T cell development and includes the necessary cis-acting sequences for extinguishing expression in the CD8 lineage. Furthermore, in mice whose endogenous CD4 gene is inactivated, the transgenic human CD4 mediates rescue of the CD4 lineage and restoration of normal helper cell functions. The generation of these mice exemplifies a general approach for developing reliable animal models for the human immune system.

Animals↗