Mapping of the human guanosine monophosphate reductase gene (GMPR) to chromosome 6p23 by fluorescence in situ hybridization.
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Cells, Cultured↗
Biomedical subjects
A Yoshida
Publications and source records attributed to A Yoshida.
Synaptotagmin can cause an immune-mediated model of Lambert-Eaton myasthenic syndrome in rats.
The possible antigenicity of synaptotagmin, a synaptic vesicle protein acting as a cooperative calcium (Ca2+) receptor in exocytosis, was tested to determine whether it is involved in the induction of Lambert-Eaton myasthenic syndrome in which antibodies against voltage-dependent Ca2+ channels or related molecules play a pathogenic role. Repeated injections to Lewis rats with peptides of synaptotagmin residues 20 through 53 or 1 through 30 that are presumably exposed at the nerve terminal surface during exocytosis induced corresponding antipeptide antibodies; on immunoblots, antibodies recognized synaptotagmin that was expressed in the clonal cells. Electrophysiologically, the peptide (residues 20-53)-immunized rats showed (1) reduced acetylcholine quantal content of end-plate potential, (2) an increase in quantal content at high extracellular Ca2+ concentration, and (3) early facilitation followed by less marked depression of end-plate potential amplitude at a tetanic rate of repetitive nerve stimulation. Findings are similar to those in human Lambert-Eaton myasthenic syndrome and passively transferred Lambert-Eaton myasthenic syndrome in mice, and thus suggest that antibody to a synaptotagmin-voltage-dependent Ca2+ channel complex may be involved in the pathogenesis of Lambert-Eaton myasthenic syndrome. The peptide (residues 1-30)-immunized rats showed no electrophysiological abnormality.
Amino Acid Sequence↗
Production of cytokines by thyroid carcinoma cell lines.
Five cell lines were established from four undifferentiated carcinomas and one squamous cell carcinoma of the thyroid. The levels of several kinds of cytokines were measured in the conditioned media of these cell lines by enzyme-linked immunosorbent assay (ELISA). Interleukin-6 (IL-6) was produced by four of the five cell lines, interleukin-1 alpha (IL-1 alpha) by three cell lines, and granulocyte-colony stimulating factor (G-CSF) by two cell lines. The mRNA of IL-1 alpha or IL-6 was detected by Northern blot analysis in all the cell lines which secreted these cytokines into culture medium. These results suggest that undifferentiated carcinoma and squamous cell carcinoma of the thyroid frequently produce cytokines. Further studies are needed to clarify the possible clinical effects of these cytokines in patients with thyroid carcinoma.
Aged↗
Alteration of tumorigenicity in undifferentiated thyroid carcinoma cells by introduction of normal chromosome 11.
The tumorigenicity of various cell lines has been shown to be suppressed by the introduction of chromosome 11 and other chromosomes via micro-cell-mediated chromosome transfer. In this study, we investigated whether a human undifferentiated thyroid carcinoma cell line, TTA-1, was suppressed by the introduction of normal human chromosome 11 or 10. Chromosome 10 or 11 was transferred from A9 cells containing a single human chromosome 10 or 11 tagged with pSV2-neo plasmid DNA into TTA-1 cells, by microcell fusion. The tumorigenicity of the TTA-1 cells and their colony-forming efficiency in soft agar were suppressed by chromosome 11, but not by chromosome 10. These results suggest that normal human chromosome 11 carries a putative tumor suppressor gene that affects the tumor-associated phenotypes of TTA-1 cells.
Animals↗
Alcohol and acetaldehyde dehydrogenase gene polymorphism and alcoholism.
Inherited variations in alcohol and aldehyde dehydrogenases, the principal enzymes of ethanol metabolism, have been implicated in determining susceptibility to alcoholism and alcohol-related organ damage. An association between an RFLP for the alcohol dehydrogenase-2 (ADH2) gene and alcohol-induced liver damage was demonstrated in a Caucasian population. Genotyping studies revealed an increase in the ADH3(2) allele in patients with alcohol-induced cirrhosis. PCR studies of the ALDH5 gene have demonstrated diverse polymorphism within a short segment of its coding region, with marked inter-racial variation in allele frequencies. In addition, the Caucasian alcohol-induced flushing reaction has been characterised and its relationship with phenotypic polymorphism of ALDH1 examined.
Alcohol Dehydrogenase↗
Influence of idarubicinol on the antileukemic effect of idarubicin.
We investigated the antileukemic potency of idarubicinol (IDAol), a 13-dihydro (13-OH) metabolite of idarubicin (IDA), on the HL60 line of human leukemia cells. In contrast to daunorubicinol (DNRol) and to doxorubicinol (DOXol), IDAol showed an extensive accumulation in HL60 cells. The high affinity for DNA and the strong DNA cleavage activity of IDAol were comparable to values for IDA; consequently, IDAol was strongly cytotoxic against HL60 cells. IDAol may play an important role in the clinical efficacy of IDA in patients with acute leukemia, particularly since it persists in the blood for prolonged periods after the administration of IDA.
DNA↗
NADPH-diaphorase in the spinal trigeminal nucleus oralis and rostral solitary tract nucleus of rats.
NADPH-diaphorase histochemical staining demonstrated a distinct neural group that might synthesize nitric oxide in the lower brainstem of rats. The NADPH-diaphorase stain revealed a Golgi-like network in the dorsomedial spinal trigeminal nucleus oralis and rostrolateral solitary tract nucleus, whereas this network was more dense in the latter nucleus. The distribution of NADPH-diaphorase-positive neurons in these areas overlapped with parts of central terminations from the chorda tympani nerve, as demonstrated with transganglionic transport of wheatgerm agglutinin conjugated horseradish peroxidase. The number of NADPH-diaphorase-positive neurons changed after chorda tympani nerve lesion relative to the contralateral side. The control value (%) was 106.0 +/- 4.9 (mean +/- S.E.M.). One hour after the nerve lesion, the value increased to 115.2 +/- 9.1 (P > 0.05). It then decreased to 83.9 +/- 5.2 two days after the lesion (P < 0.05), and remained at this reduced level for one or two weeks, 83.2 +/- 3.0 (P < 0.01) and 83.7 +/- 2.3 (P < 0.01), respectively. This statistically significant reduction recovered to control level 103.4 +/- 2.9 four weeks after the lesion. These results show that NADPH-diaphorase-positive neurons in the lower brainstem could be regulated trans-synaptically by primary afferents, possibly gustatory inputs.
Animals↗
Quantitative circulatory measurements in branch retinal vessel occlusion.
We used the laser Doppler technique to quantify retinal circulatory abnormalities in three patients with branch retinal artery occlusion and in two patients with branch retinal vein occlusion, each of whom had shown delayed filling on fluorescein angiography. Blood flow in occluded arteries was 40-50% lower than in non-occluded arteries of the same branching order. In the patients with branch retinal vein occlusion blood flow in arteries supplying the affected regions was 80-90% lower than in arteries supplying the unaffected regions. One vein occlusion patient was measured serially over 18 months. Blood flow increased from 4 to 12 microliters/min in the artery supplying the affected region in this patient. The results demonstrate that retinal circulatory abnormalities can be evaluated quantitatively during the course of retinal vascular occlusive disease, and suggest that the efficacy of therapy can be monitored using our techniques.
Aged↗
Swelling-activated and isoprenaline-activated chloride currents in guinea pig cardiac myocytes have distinct electrophysiology and pharmacology.
We have used the whole-cell patch clamp recording technique to characterize a swelling-activated chloride current in guinea pig atrial and ventricular myocytes and to compare the electrophysiological and pharmacological properties of this current with the isoprenaline-activated chloride current in the same cell types. Osmotic swelling of guinea pig cardiac myocytes caused activation of an outwardly rectifying, anion-selective current with a conductance and permeability sequence of I- approximately NO3- > Br- > Cl- > Asp-. This current was inhibited by tamoxifen, 4,4'-diisothiocyano-stilbene-2,2'-disulphonate and anthracene-9-carboxylic acid, in decreasing order of potency. The isoprenaline-activated anion current, like the swelling-activated current, had a higher permeability to I- relative to Cl-, but it had a markedly reduced conductance for I- compared to Cl-. The isoprenaline-activated current was insensitive to inhibition by tamoxifen, 4,4'-diisothiocyanostilbene-2,2'-disulphonate and anthracene-9-carboxylic acid. The swelling-activated current could be elicited in > 90% atrial myocytes studied but only 34% ventricular myocytes. Conversely, the isoprenaline-activated current was elicited in < 10% atrial myocytes and > 90% ventricular myocytes. In those ventricular myocytes where it was possible to elicit swelling-activated and isoprenaline-activated currents simultaneously, the currents retained the same distinguishing characteristics as when they were elicited in isolation. Thus, while guinea pig atrial cells appear to preferentially express swelling-activated chloride channels and guinea pig ventricular myocytes preferentially express isoprenaline-activated chloride channels, the presence of these two channel types are not necessarily mutually exclusive. This raises the possibility that there may be coordinated regulation of the expression of different Cl- channels within the heart.
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
Endometrial carcinogenesis induced by concurrent oral administration of ethylenethiourea and sodium nitrite in mice.
Endometrial carcinogenesis induced by concurrent oral administration of ethylenethiourea (ETU) and sodium nitrite (NaNO2) was investigated in ICR (Crj:CD-1) female mice. A mixed solution of ETU (100 mg/kg) and NaNO2 (70 mg/kg) was given to animals orally once a week for up to 6 months and all surviving animals were killed at 12 months of study. During the study, estrous cycle was monitored by vaginal smear and five or 10 selected animals were subjected to interim killing at 3 month interval to observe time-related carcinogenic responses of the uterus. Treatment with ETU and NaNO2 resulted in development of endometrial adenocarcinomas in the uterine horn and the incidence reached 42% in the surviving animals at 12 months. Prior to the development of the tumor, atypical hyperplasia of endometrial glands was frequently observed and regarded as the precancerous lesion. Immunohistochemistry for bromodeoxyuridine (BrdU) incorporation revealed higher labeling indices in both hyperplastic and neoplastic endometrial glandular cells, and the index in the adenocarcinoma was more than 20% on average at any stage of the estrous cycle. Overexpression of p53 protein, which is frequently demonstrated in virulent phenotypes of human corpus cancers, was seen in three out of eight (38%) adenocarcinomas, but not in the atypical hyperplasia or normal endometrial glands. There were no treatment-related changes in the estrous cycle on vaginal smears at any interval of the study. The analyses for plasma ovarian hormones at 12 months disclosed a marked depression of progesterone in the treated animals, while the 17 beta-estradiol (E2) level was comparable to the controls. These results suggest that endometrial carcinogenesis by ETU and NaNO2 could be initiated with atypical hyperplasia of the endometrial gland and a decrease in plasma progesterone level may play an important role in the development of endometrial carcinogenesis. In addition, inactivation of the p53 gene may play a significant role in the malignant transformation of endometrial epithelial cells in mice.
Adenocarcinoma↗
The signal transduction mechanism responsible for gamma interferon-induced indoleamine 2,3-dioxygenase gene expression.
We examined the signal transduction mechanism responsible for the gamma interferon-induced indoleamine 2,3-dioxygenase (IDO) gene expression in a human monocytic cell line, THP-1. Our results suggest that gamma interferon-induced activation of protein tyrosine kinase is a prerequisite for gene expression and that activation of protein kinase C and another unknown signal(s), both of which are transduced by the protein tyrosine kinase, synergistically induce IDO gene expression. Neither Ca2+ influx nor cyclic nucleotide-dependent kinases were suggested to be involved in the signaling pathway.
Base Sequence↗
High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells.
We demonstrate a significantly high incidence of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM)-or tropical spastic paraparesis (TSP)-like symptoms in WKA rats after injection with HTLV-1-producing MT-2 cells, while no symptoms were observed in F344 rats injected with MT-2 cells or in control WKA rats. Five of the eight (63%) WKA rats injected with MT-2 cells showed HAM/TSP-like paraparesis at 105 weeks of age, but none of seven MT-2-injected F344 rats or eight control WKA rats showed symptoms. This high incidence of HAM/TSP-like symptoms in WKA rats was statistically significant (P < 0.05). Six of the eight (75%) WKA rats injected with MT-2 cells showed HAM/TSP-like paraparesis at 108 weeks of age. HAM/TSP-like symptoms were also observed in one of the two WKA rats injected with HTLV-1-producing Ra-1 cells at 128 weeks of age. HTLV-1 provirus was detected in peripheral blood mononuclear cells in both WKA and F344 rats. The provirus was detected in the spinal cords of the HAM/TSP-like WKA rats that had severe neuropathological changes. WKA and F344 rats showed no significant difference in antibody response against HTLV-1 Gag antigen. However, the antibody response against the C-terminal half of gp46 HTLV-1 envelope protein was lower in WKA rats than in F344 rats. Pathological analysis of the HAM/TSP-like rats showed degeneration of the white matter of the spinal cord and peripheral nerves. These findings suggest that both the genetic background of the host and HTLV-1 infection are important in neuropathogenesis of HAM/TSP-like paraparesis in rats.
Animals↗
Effect of growth hormone and insulin-like growth factor-I on immunoglobulin production by and growth of human B cells.
The effect of human GH and insulin-like growth factor-I (IGF-I) on immunoglobulin (Ig) production by and proliferation of human B cells was studied in serum- and hormone-free medium. GH enhanced the production of Ig by and thymidine uptake of the human lymphoblastoid B cell lines, CBL and GM-1056. IGF-I, but not IGF-II or insulin, also enhanced Ig production by and proliferation of CBL and GM-1056. However, the GH-induced enhancement was not mediated by IGF-I inasmuch as enhancement was blocked by anti-GH antibody but not by anti-IGF-I antibody or anti-IGF-I receptor antibody. Conversely, the IGF-I-induced enhancement was blocked by either anti-IGF-I antibody or anti-IGF-I receptor antibody but not by anti-GH antibody. GH and IGF-I also enhanced Ig production by and proliferation of the human lymphoblastoid B cell lines, CESS, GM-1500, SKW, and GM-3332. Furthermore, GH and IGF-I enhanced production of IgG1, IgG2, IgG3, IgG4, IgA1 IgA2, and IgM by and thymidine uptake of tonsillar B cells stimulated with Staphylococcus aureus Cowan strain I. Again, the GH-induced enhancement was blocked by anti-GH antibody whereas the IGF-I-induced enhancement was blocked by either anti-IGF-I antibody or anti-IGF-I receptor antibody but not vice versa.
B-Lymphocytes↗
Induction of cytochrome P-450s and expression of liver-specific genes in rat primary hepatocytes cultured on different extracellular matrices.
Freshly isolated hepatocytes were cultured on an EHS-gel prepared from EHS-tumor, poly-N-p-vinylbenzyl-D-lactonamide (PVLA), and type I collagen (TIC). Hepatocytes on EHS-gel showed a spherical shape and much more strongly maintained the inducible expression of cytochrome P-450 genes which were lost on PVLA and TIC. Further, the expression of liver-specific genes were maintained on EHS gel at the highest level, and then higher on PVLA than TIC.
Animals↗
Cholera toxin can ADP-ribosylate Gs as well as Gi in ACTH-unresponsive human adrenocortical cancer.
It is well known that cholera toxin (CT) stimulates ADP-ribosylation of Gs and also pertussis toxin (PT) does Gi. Each GTP-binding protein has its own action in the regulation of adenylate cyclase. A human non-functioning adrenocortical cancer tissue showed an unresponsiveness in adenylate cyclase to ACTH although ACTH and CT activated adenylate cyclase in a non-functioning adrenal adenoma tissue. CT ADP-ribosylated 43 kDa protein of the plasma membrane of the cancer tissue while CT and PT could ADP-ribosylate 43 kDa and 38 kDa protein in the adenoma tissue, respectively. Immunoblotting analysis of the cancer tissue demonstrated that 40 kDa protein was detected by anti-Gs antibody as well as by anti-Gi antibody. The present experiments demonstrated that CT could ADP-ribosylate Gs which has stimulatory action on adenylate cyclase and also Gi which inhibits adenylate cyclase. Thus it is suggested that CT can activate the ADP-ribosylation of Gs and also Gi in a human adrenocortical cancer tissue, partly resulting in abnormal regulation of adenylate cyclase which may be crossly related to ACTH-unresponsiveness.
Adenoma↗
Study of hereditary trends in the shape of the murine mandible.
Inbred mice are a suitable material for genetic studies, and mandibular shape in particular provides a highly quantitative hereditary trait. We investigated which genetic trait in F1, F2 and N2 hybrid mice was most strongly affected by the presence of a large or small mandible in the parents. Ten C57BL/6By strain mice as parents with a small mandible and 10 MRL/n strain mice as parents with a large mandible were employed. Twenty-five (C57BL/6By male X MRL/n female) F1 and 67 F2 hybrids, and 28 (F1 male X C57BL/6By female) N2 backcross hybrids were obtained by laboratory mating. The inter-landmarks of the right mandible were measured by an electronic digitizer. Each mean value of horizontal dimensions in F1 mice resembled that in MRL/l mice, and that in N2 mice was intermediate between C57BL/6By and MRL/n mice. On the other hand, the mean values of vertical dimensions in F1, F2 and N2 hybrids were intermediate between those of C57BL/6By and MRL/n mice. Hence we suggest that horizontal dimensions are predominantly inherited by mice with a large mandible, and that vertical dimensions show intermediate inheritance between mice with large and small mandibles in the C57BL/6By and MRL/n strains.
Animals↗
Genetic polymorphisms of alcohol metabolizing enzymes related to alcohol sensitivity and alcoholic diseases.
Individuals with the atypical aldehyde dehydrogenase ALDH2 allele, both homozygous and heterozygous status, are alcohol sensitive and have a markedly reduced risk of developing alcoholic diseases. Genetic abnormalities of the ALDH1 locus are also associated with alcohol flushing. The ALDH3 and ALDHx loci are polymorphic and their variations may affect the development of alcoholic diseases. The variations of alcohol dehydrogenase ADH2 and ADH3 loci have no profound effects on alcohol sensitivity. The newly identified ADH6 gene has hormone response elements, and it may cause the gender difference in alcoholic problems.
Alcoholism↗
[Effect of sevoflurane on blood flow velocity in the vertebral artery].
Blood flow velocity in the vertebral artery was measured using transcranial Doppler sonography during sevoflurane anesthesia in 12 patients in the knee-chest position. The correlation between mean arterial blood pressure (MBP) and mean blood flow velocity in the vertebral artery (Vmean) was significant in each patient. Normalized data expressed as a percentage of the individual arithmetic means permitted a composite analysis of data from all patients. Linear regression of normalized MBP (%MBP) on normalized Vmean (%Vmean) showed %Vmean = 24.8 +/- 0.75 %MBP (r = 0.78, P < 0.01). The results of the present study suggest that fluctuations in systemic blood pressure may lead to fluctuations in cerebral blood flow. Therefore, the use of sevoflurane anesthesia must be accompanied by careful management of blood pressure during surgery.
Adult↗