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2.
Nature ; 620(7976): 965-970, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37648757

ABSTRACT

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

3.
Phys Rev Lett ; 125(12): 122501, 2020 Sep 18.
Article in English | MEDLINE | ID: mdl-33016755

ABSTRACT

We performed the first direct mass measurements of neutron-rich scandium, titanium, and vanadium isotopes around the neutron number 40 at the RIKEN RI Beam Factory using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{58-60}Sc, ^{60-62}Ti, and ^{62-64}V were measured for the first time. The experimental results show that the two-neutron separation energies in the vicinity of ^{62}Ti increase compared to neighboring nuclei. This shows that the masses of Ti isotopes near N=40 are affected by the Jahn-Teller effect. Therefore, a development of Jahn-Teller stabilization appears below the Cr isotopes, and the systematics in Sc, Ti, and V isotopes suggest that ^{62}Ti is located close to the peak of the Jahn-Teller effect.

4.
Phys Rev Lett ; 124(21): 212502, 2020 May 29.
Article in English | MEDLINE | ID: mdl-32530645

ABSTRACT

The structure of a neutron-rich ^{25}F nucleus is investigated by a quasifree (p,2p) knockout reaction at 270A MeV in inverse kinematics. The sum of spectroscopic factors of π0d_{5/2} orbital is found to be 1.0±0.3. However, the spectroscopic factor with residual ^{24}O nucleus being in the ground state is found to be only 0.36±0.13, while those in the excited state is 0.65±0.25. The result shows that the ^{24}O core of ^{25}F nucleus significantly differs from a free ^{24}O nucleus, and the core consists of ∼35% ^{24}O_{g.s.}. and ∼65% excited ^{24}O. The result may infer that the addition of the 0d_{5/2} proton considerably changes neutron structure in ^{25}F from that in ^{24}O, which could be a possible mechanism responsible for the oxygen dripline anomaly.

5.
Phys Rev Lett ; 124(15): 152502, 2020 Apr 17.
Article in English | MEDLINE | ID: mdl-32357034

ABSTRACT

Detailed spectroscopy of the neutron-unbound nucleus ^{28}F has been performed for the first time following proton/neutron removal from ^{29}Ne/^{29}F beams at energies around 230 MeV/nucleon. The invariant-mass spectra were reconstructed for both the ^{27}F^{(*)}+n and ^{26}F^{(*)}+2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the ^{28}F ground state, with S_{n}(^{28}F)=-199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S_{n}(^{27}F)=1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of ^{28}F. Importantly, in the case of the ground state, the reconstructed ^{27}F+n momentum distribution following neutron removal from ^{29}F indicates that it arises mainly from the 1p_{3/2} neutron intruder configuration. This demonstrates that the island of inversion around N=20 includes ^{28}F, and most probably ^{29}F, and suggests that ^{28}O is not doubly magic.

6.
Phys Rev Lett ; 121(2): 022506, 2018 Jul 13.
Article in English | MEDLINE | ID: mdl-30085708

ABSTRACT

We perform the first direct mass measurements of neutron-rich calcium isotopes beyond neutron number 34 at the RIKEN Radioactive Isotope Beam Factory by using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{55-57}Ca are determined for the first time to be -18650(160), -13510(250), and -7370(990) keV, respectively. We examine the emergence of neutron magicity at N=34 based on the new atomic masses. The new masses provide experimental evidence for the appearance of a sizable energy gap between the neutron 2p_{1/2} and 1f_{5/2} orbitals in ^{54}Ca, comparable to the gap between the neutron 2p_{3/2} and 2p_{1/2} orbitals in ^{52}Ca. For the ^{56}Ca nucleus, an open-shell property in neutrons is suggested.

7.
Phys Rev Lett ; 120(17): 172501, 2018 Apr 27.
Article in English | MEDLINE | ID: mdl-29756826

ABSTRACT

The (^{12}N, ^{12}C) charge-exchange reaction at 175 MeV/u was developed as a novel probe for studying the isovector spin giant monopole resonance (IVSMR), whose properties are important for better understanding the bulk properties of nuclei and asymmetric nuclear matter. This probe, now available through the production of ^{12}N as a secondary rare-isotope beam, is exothermic, is strongly absorbed at the surface of the target nucleus, and provides selectivity for spin-transfer excitations. All three properties enhance the excitation of the IVSMR compared to other, primarily light-ion, probes, which have been used to study the IVSMR thus far. The ^{90}Zr(^{12}N,^{12}C) reaction was measured and the excitation energy spectra up to about 70 MeV for both the spin-transfer and non-spin-transfer channels were deduced separately by tagging the decay by γ emission from the ^{12}C ejectile. Besides the well-known Gamow-Teller and isobaric analog transitions, a clear signature of the IVSMR was identified. By comparing with the results from light-ion reactions on the same target nucleus and theoretical predictions, the suitability of this new probe for studying the IVSMR was confirmed.

8.
Phys Rev Lett ; 120(15): 152505, 2018 Apr 13.
Article in English | MEDLINE | ID: mdl-29756883

ABSTRACT

We observed the atomic 1s and 2p states of π^{-} bound to ^{121}Sn nuclei as distinct peak structures in the missing mass spectra of the ^{122}Sn(d,^{3}He) nuclear reaction. A very intense deuteron beam and a spectrometer with a large angular acceptance let us achieve a potential of discovery, which includes the capability of determining the angle-dependent cross sections with high statistics. The 2p state in a Sn nucleus was observed for the first time. The binding energies and widths of the pionic states are determined and found to be consistent with previous experimental results of other Sn isotopes. The spectrum is measured at finite reaction angles for the first time. The formation cross sections at the reaction angles between 0° and 2° are determined. The observed reaction-angle dependence of each state is reproduced by theoretical calculations. However, the quantitative comparison with our high-precision data reveals a significant discrepancy between the measured and calculated formation cross sections of the pionic 1s state.

9.
Phys Rev Lett ; 116(5): 052501, 2016 Feb 05.
Article in English | MEDLINE | ID: mdl-26894705

ABSTRACT

A candidate resonant tetraneutron state is found in the missing-mass spectrum obtained in the double-charge-exchange reaction ^{4}He(^{8}He,^{8}Be) at 186 MeV/u. The energy of the state is 0.83±0.65(stat)±1.25(syst) MeV above the threshold of four-neutron decay with a significance level of 4.9σ. Utilizing the large positive Q value of the (^{8}He,^{8}Be) reaction, an almost recoilless condition of the four-neutron system was achieved so as to obtain a weakly interacting four-neutron system efficiently.

10.
Radiat Prot Dosimetry ; 165(1-4): 439-42, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25889608

ABSTRACT

Many people are anxious about radiation exposure for the reason that radiation cannot be seen. With the aim of devising a way for medical personnel to perform their medical duties without worry about radiation exposure, we attempted safety management using a system that displays the air dose of radiation in real time. Measurements were made in a lung ventilation scintigraphy examination room with the use of Xe-133. An SCI-type RI detector from Hamamatsu Photonics, which displays the air dose rate in real time, was used for the measurements. These radiation measurements were continued from the start to finish of the examination. The measurements were made in two locations, on the patient inhalation tube side and on the opposite side. Measurements were made on the patient tube side in 24 tests and on the opposite side in 12 tests. The maximum air dose rate was 3.7 ± 2.1 µSv/h on the patient tube side and 1.1 ± 0.5 µSv/h on the opposite side. Thus, the level on the opposite side was about 1/5 that of the tube side. To accurately perform lung ventilation scintigraphy, a medical worker needs to observe the patient's breathing status up close. Because of this, some medical workers are worried about radiation exposure during tests. The simplest way to reduce exposure would be to maintain a distance from the examination tube that is the source of radiation. The measurements in this study were made to encourage medical workers' recognition of this fact. Displaying specific numbers not only serves as basic data for managing staff operations, but is also thought to reassure workers through visualization.


Subject(s)
Nuclear Medicine , Occupational Health , Radiation Dosage , Safety Management , Air , Air Pollutants/analysis , Equipment Design , Gases , Humans , Occupational Exposure , Photons , Radiation Monitoring/methods , Radiation Protection/methods , Radioactive Pollutants/analysis , Radiometry , Radionuclide Imaging/methods , Radiopharmaceuticals/adverse effects , Respiration , Risk , Workforce , Xenon
11.
J Helminthol ; 88(1): 24-31, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23137748

ABSTRACT

Human alveolar echinococcosis (AE) is caused by the accidental ingestion of Echinococcus multilocularis eggs. Early detection is essential as surgical resection is the only treatment for a complete cure. However, details are unclear about changes in the antibody response during the initial stages of infection, yet such information is useful for early serodiagnosis. Therefore, a long-term investigation was performed into the time course of the antibody response before 'positive' detection. Patient sera were used for enzyme-linked immunosorbent assay (ELISA) and Western blotting (WB) analysis using crude antigens extracted from E. multilocularis protoscoleces. Rats were experimentally infected with AE and similarly analysed by ELISA and WB. Among the markers for diagnoses, the 18 kDa band (main marker) appeared last in the preoperative stages and disappeared first after operation in a WB test. Although the 18 kDa antigen can be useful as a marker for AE diagnosis, it cannot contribute to the detection of some patients before the 18 kDa band appearance. To avoid misdiagnosis, different diagnostic antigens such as the 26-28 and 7-8 kDa bands should also be considered. These bands tend to appear earlier than the 18 kDa band and thus offer the potential for early detection of AE. We first observed changes in the antibody response in a relatively early stage after infection in human AE cases. Notably, changes in the antibody response of two intermediate species were similar. These findings provide valuable information for the early detection of human AE cases in the future.


Subject(s)
Antibodies, Helminth/blood , Echinococcosis, Hepatic/immunology , Echinococcus multilocularis/immunology , Aged , Animals , Antigens, Helminth/immunology , Blotting, Western , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Rats , Rats, Inbred F344 , Time Factors
12.
Phys Rev Lett ; 108(26): 262503, 2012 Jun 29.
Article in English | MEDLINE | ID: mdl-23004971

ABSTRACT

The double-differential cross sections for the (208)Pb and (90)Zr(t,(3)He) reactions at 300 MeV/u have been measured at the RI Beam Factory at RIKEN. This was the first physics experiment with the SHARAQ magnetic spectrometer. The combined analysis of the present (t,(3)He) data and previous (n,p) data provides the clearest identification for the ß(+) isovector spin monopole resonance both in the (208)Tl and (90)Y nuclei, and puts the observations of this giant resonance on a firm foundation. The measured distributions of the (t,(3)He) monopole cross sections were well reproduced by the distorted-wave Born approximation calculation, where the target transition density was calculated with the self-consistent Hartree-Fock plus random-phase approximation using the T43 Skyrme interaction. A major part of the expected ß(+) isovector spin monopole strength was found in the measured cross section spectra.

13.
Scand J Gastroenterol ; 39(10): 919-26, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15513328

ABSTRACT

BACKGROUND: Among inbred female cotton rats (Sigmodon hispidus) 25%-50% of the animals develop spontaneous gastric carcinomas, whereas males have an incidence of less than 1%. The carcinomas are enterochromaffin-like (ECL)-cell derived. Animals with gastric carcinomas also have hypergastrinaemia and gastric hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have been found in all female cotton rats with spontaneous hypergastrinaemia lasting more than 4 months, and a gastrin receptor antagonist prevents the development of carcinoma. The purpose of the present study was to investigate whether induced hypergastrinaemia in male cotton rats would also result in carcinomas. METHODS: Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming at removal of 80%-90% of the corpus. A control group was sham-operated. RESULTS: All partially corpectomized animals developed persistent hypergastrinaemia. Six months after the operation, 9 out of 13 partially corpectomized animals developed gastric cancer. In the dysplastic mucosa surrounding the tumours there was an increase in chromogranin A immunoreactive cells, where numerous cells also were stained using the Sevier-Munger technique. Tumour tissue also contained cells that were chromogranin A positive and stained by Sevier-Munger. CONCLUSIONS: ECL-cell carcinomas can be induced in male cotton rats by partial corpectomy. This supports a previous statement that spontaneous carcinomas in female cotton rats are caused by gastric hypoacidity and hypergastrinaemia. In hypergastrinaemic animals, ECL-cell carcinomas develop independently of gender within a relatively short period of time, and cotton rats therefore represent an interesting model for studying gastric carcinogenesis.


Subject(s)
Carcinoma/pathology , Enterochromaffin-like Cells/pathology , Gastrins/metabolism , Stomach Neoplasms/pathology , Animals , Biopsy, Needle , Disease Models, Animal , Gastrectomy/methods , Gastrins/blood , Hydrogen-Ion Concentration , Immunohistochemistry , Male , Probability , Rats , Sensitivity and Specificity , Sigmodontinae , Statistics, Nonparametric
14.
Endocr Relat Cancer ; 11(1): 149-60, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15027892

ABSTRACT

Among inbred female cotton rats (Sigmodon hispidus) 25-50% of the animals develop spontaneous gastric carcinomas; the corresponding figure for male cotton rats is approximately 1%. Animals with carcinomas have hypergastrinaemia and gastric hypo-anacidity and the tumours are derived from enterochromaffin-like (ECL) cells. The mechanism behind the hypo-anacidity is unknown. Carcinomas are found in all female cotton rats with hypergastrinaemia lasting more than 4 months and this represents an excellent animal model for studying gastric carcinogenesis. In this study, the somatostatin analogue octreotide was given to female cotton rats to prevent carcinoma development caused by hypergastrinaemia. Twelve female cotton rats were given monthly injections of long-acting octreotide (5 mg i.m.) for 6 months. A control group of 20 animals was not given injections. Of the 20 control animals, 13 developed hypergastrinaemia and histologically invasive carcinomas or dysplasia. Of the 12 animals in the octreotide group, five developed hypergastrinaemia. None of these five animals developed histological cancer (P<0.05), whereas three had dysplasia. However, octreotide did not affect plasma gastrin concentration or antral gastrin mRNA abundance significantly. Dysplasia of the oxyntic mucosa in hypergastrinaemic animals was accompanied by a marked increase in chromogranin A-immunoreactive cells and cells positive for Sevier-Munger staining. The malignant tissue also contained groups of cells with Sevier-Munger staining. In conclusion, octreotide prevented ECL cell carcinomas in hypergastrinaemic cotton rats without lowering the gastrin concentration.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Carcinoma/prevention & control , Enterochromaffin-like Cells/pathology , Octreotide/therapeutic use , Stomach Neoplasms/prevention & control , Animals , Carcinoma/metabolism , Carcinoma/pathology , Chromogranin A , Chromogranins/metabolism , Enterochromaffin-like Cells/metabolism , Female , Gastrins/blood , Gastrins/metabolism , Immunochemistry , Parietal Cells, Gastric/metabolism , Parietal Cells, Gastric/pathology , RNA, Messenger/analysis , RNA, Messenger/metabolism , Rats , Sigmodontinae , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology
15.
Talanta ; 53(5): 1037-44, 2001 Jan 26.
Article in English | MEDLINE | ID: mdl-18968195

ABSTRACT

Nickel-titanium (Ni-Ti) alloy electrode was used as an electrochemical detector for the analysis of underivatized amino acids in flow systems. In strong alkaline solution, an oxide film on the Ni-Ti alloy electrode surface exhibited a high catalytic activity toward the oxidation of amino acids. Cyclic voltammetry experiments confirmed that electrogenerated Ni(III)O(OH) functioned as the key redox mediator associated with the oxidation of the amine group in amino acids. The electrochemical behavior of the Ni-Ti electrode in alkaline medium was very similar to the Ni electrode. However, the oxide film was found to be much stable on Ni-Ti than on Ni. Consequently, the Ni-Ti alloy electrode exhibited an excellent stability for constant-potential amperometric detection of amino acids in flow systems. For example, the relative standard deviation (R.S.D.) for the repetitive 100 injections of 50 muM (1.2 nmol) glycine over 10 h was less than 1%. It was postulated that the presence of Ti in the alloy stabilizes the microstructure of oxide layer on the electrode surface. The sensitivities of amino acids at the electrode were different, depending on their chemical structures. The detection limits obtained in a range from 0.9 pmol for arginine to 90.2 pmol for leucine and isoleucine. The Ni-Ti alloy electrodes have been demonstrated to be very suitable for the amperometric detection of underivatized amino acids in anion-exchange chromatography.

16.
J Telemed Telecare ; 6 Suppl 2: S69-71, 2000.
Article in English | MEDLINE | ID: mdl-10975109

ABSTRACT

We examined the effect of distance learning on nurses' clinical skills in a rural Japanese hospital. The subject matter was respiratory rehabilitation. After one face-to-face session, who 30 min sessions were delivered by videoconferencing to staff nurses working in a 100-bed rural hospital 250 miles (400 km) from Sapporo Medical University. A self-rating questionnaire was distributed before and after the sessions. Responses were collected from 15 out of 32 nurses participating in the face-to-face session (47%). Before the first videoconferencing session, 'always use' and 'sometime use' the new skills were rated by 67% of nurses, but after the second videoconferencing session 'always use' and 'sometimes use' were rated by 73% and 'never use' at 0%. This implies that there was increased use of new skills after the second session, although the difference was not significant. The nurses' opinions about the effectiveness for patients increased from 8% to 27% after the second session, which was significant. The pilot project indicated the usefulness of distance learning for upgrading nurses' clinical practice in one rural Japanese hospital and suggested ways in which videoconferencing can be used in future.


Subject(s)
Education, Distance/methods , Education, Nursing, Continuing/methods , Respiration Disorders/rehabilitation , Attitude of Health Personnel , Education, Distance/standards , Education, Nursing, Continuing/standards , Humans , Japan , Pilot Projects , Rural Health Services , Surveys and Questionnaires , Telemedicine/methods , Video Recording
17.
Protein Eng ; 13(8): 557-63, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10964985

ABSTRACT

Arginines R23, R178, R179 and R218 in thymidylate synthase (TS, EC 2. 1.1.45) are hydrogen bond donors to the phosphate moiety of the substrate, dUMP. In order to investigate how these arginines contribute to enzyme function, we prepared complete replacement sets of mutants at each of the four sites in Lactobacillus casei TS. Mutations of R23 increase K:(m) for dUMP 2-20-fold, increase K:(m) for cofactor 8-40-fold and decrease k(cat) 9-20-fold, reflecting the direct role of the R23 side chain in binding and orienting the cofactor in ternary complexes of the enzyme. Mutations of R178 increase K:(m) for dUMP 40-2000-fold, increase K:(m) for cofactor 3-20-fold and do not significantly affect k(cat). These results are consistent with the fact that this residue is an integral part of the dUMP-binding wall and contributes to the orientation and ordering of several other dUMP binding residues. Kinetic parameters for all R179 mutations except R179P were not significantly different from wild-type values, reflecting the fact that this external arginine does not directly contact the cofactor or other ligand-binding residues. R218 is essential for the structure of the catalytic site and all mutations of this arginine except R218K were inactive.


Subject(s)
Arginine/metabolism , Phosphates/metabolism , Thymidylate Synthase/chemistry , Genetic Complementation Test , Kinetics , Mutagenesis, Insertional , Thymidylate Synthase/metabolism
18.
Analyst ; 125(6): 1041-3, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10932850

ABSTRACT

An indirect amperometric detection of underivatized amino acids has been developed using a carbon film based ring-disk electrode (CFBRDE) in microcolumn liquid chromatography (LC). Bromide present in the mobile phase could be efficiently oxidized to bromine at the upstream (disk) electrode, and was subsequently detected at the downstream (ring) electrode. Most of the underivatized amino acids that are electroinactive under conventional amperometric conditions react rapidly with the electrogenerated bromine, the concentration of amino acids can therefore be indirectly determined by continuously monitoring the reduction current of bromine. The signal monitored at the downstream electrode was largely dependent on the bromide concentration in the mobile phase. Under optimized conditions, the response linearly increased with the concentration for most of the amino acids over a concentration range of 1-100 microM, with a correlation coefficient of 0.990-0.993. The detection limits for most of the amino acids were below 1 microM (0.2 pmol). It was demonstrated that detection with a ring-disk electrode offers the advantages of achieving a much higher collection efficiency caused by a decrease in flow rate in the microcolumn LC.


Subject(s)
Amino Acids/analysis , Bromine/analysis , Chromatography, Liquid/methods , Electrochemistry , Microelectrodes , Sensitivity and Specificity
19.
Biochemistry ; 39(5): 1011-20, 2000 Feb 08.
Article in English | MEDLINE | ID: mdl-10653645

ABSTRACT

In thymidylate synthase, four conserved arginines provide two hydrogen bonds each to the oxygens of the phosphate group of the substrate, 2'-deoxyuridine-5'-monophosphate. Of these, R23, R178, and R179 are far removed from the site of methyl transfer and contribute to catalysis solely through binding and orientation of ligands. These arginines can be substituted by other residues, while still retaining more than 1% activity of the wild-type enzyme. We compared the kinetics and determined the crystal structures of dUMP complexes of three of the most active, uncharged single mutants of these arginines, R23I, R178T, and R179T, and of double mutants (R23I, R179T) and (R178T, R179T). The dramatically higher K(m) for R178T compared to the other two single mutants arises from the effects of R178 substitution on the orientation of dUMP; 10-15-fold increases in for R23I and R178T reflect the role of these residues in stabilizing the closed conformation of TS in ternary complexes. The free energy for productive dUMP binding, DeltaG(S), increases by at least 1 kcal/mol for each mutant, even when dUMP orientation and mobility in the crystal structure is the same as in wild-type enzyme. Thus, the four arginines do not contribute excess positive charge to the PO(4)(-2) binding site; rather, they ideally complement the charge and geometry of the phosphate moiety. More-than-additive increases in DeltaG(S) seen in the double mutants are consistent with quadratic increases in DeltaG(S) predicted for deviations from ideal electrostatic interactions and may also reflect cooperative binding of the arginines to the phosphate oxygens.


Subject(s)
Arginine/chemistry , Phosphates/metabolism , Thymidylate Synthase/chemistry , Arginine/genetics , Arginine/metabolism , Binding Sites/genetics , Crystallography, X-Ray , Deoxyuracil Nucleotides/chemistry , Deoxyuracil Nucleotides/metabolism , Hydrogen Bonding , Kinetics , Lacticaseibacillus casei/enzymology , Mutagenesis, Site-Directed , Static Electricity , Structure-Activity Relationship , Thermodynamics , Threonine/genetics , Thymidylate Synthase/metabolism
20.
Carcinogenesis ; 21(1): 23-7, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10607729

ABSTRACT

We have identified cotton rats with a high female-predominant occurrence of spontaneous gastric carcinomas localized to the oxyntic mucosa, classified as malignant enterochromaffin-like (ECL) omas. The present study was made to further characterize these ECLomas and surrounding oxyntic mucosa, both morphologically using histochemical and immunohistochemical methods, and for gene expression by northern blot analysis. Among eight female cotton rats, three had an irregularly thickened oxyntic mucosa, increased stomach weight and a high serum gastrin level. Histopathological examination showed adenomatous hyperplasia of the thickened oxyntic mucosa with areas of an invasive neoplastic tumour. Immunohistochemistry, using the general neuroendocrine cell marker chromogranin A (CgA) and the specific ECL cell marker histidine decarboxylase (HDC), showed a considerably increased ECL cell density. These ECL cells displayed active proliferation, with hyperplasia, dysplasia and neoplasia. Parietal cells were not found in the tumour tissue. Parietal cell density was only slightly reduced in the surrounding oxyntic mucosa. The antral mucosa was histopathologically normal with a normal number of gastrin-immunoreactive cells. Likewise, somatostatin-immunoreactive cells did not show any differences in the antral and oxyntic mucosa between rats with pathological and normal oxyntic mucosa. Northern blot analysis revealed increased expression of CgA and HDC mRNA in the thickened oxyntic mucosa, whereas H(+)/K(+) ATPase mRNA was similar in the oxyntic mucosa of those with thickened and normal oxyntic mucosa. Gastrin mRNA in the antral mucosa was high in animals with thickened oxyntic mucosa. Somatostatin mRNA expression was similar in the antral mucosa of control animals and animals with a thickened oxyntic mucosa. We conclude that the spontaneous gastric carcinoma occurring in female cotton rats is an ECLoma developing secondary to hypergastrinaemia due to reduced intragastric pH. The mechanism for reduced acidity is not known, but is not gastric atrophy.


Subject(s)
Enterochromaffin Cells/pathology , Gastrins/blood , Parietal Cells, Gastric/pathology , Rodent Diseases/etiology , Sigmodontinae , Stomach Neoplasms/veterinary , Animals , Blotting, Northern , Chromogranin A , Chromogranins/analysis , Chromogranins/genetics , Female , Gastric Acidity Determination , H(+)-K(+)-Exchanging ATPase/metabolism , Histidine Decarboxylase/genetics , Immunohistochemistry , RNA, Messenger/analysis , Rodent Diseases/pathology , Somatostatin/genetics , Stomach Neoplasms/etiology , Stomach Neoplasms/pathology
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