Outlook for a database system in gastroenterology from a health care standpoint.
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Biomedical subjects
Publications and source records attributed to S Fujimoto.
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The role of the submandibular glands in the excretion of parenterally administered bis (tributyltin) oxide (TBTO) was studied. Fine structural alterations of the submandibular glands were observed with an electron microscope. Accumulation sites of TBTO were determined with an X-ray microanalyzer and tin concentrations in saliva and blood were measured by atomic absorption spectrophotometry.
To discover whether hypoxia affects mediator responses and neurotransmission in tracheal smooth muscle, we studied in vitro tracheal segments from guinea-pigs under isometric conditions. Hypoxia itself did not alter the basal tone. The maximum response to acetylcholine and histamine under hypoxia was less than that under oxygenated conditions. The logarithm of 50% effective concentration (log EC50) of the response to acetylcholine under hypoxia was not altered, but the log EC50 of the response to histamine decreased significantly. In contrast to the response to exogenous acetylcholine, the maximum contractile response to electrical field stimulation (EFS) under hypoxia was not different from that under oxygenated conditions, but the logarithm of 50% effective frequency of contractions caused by EFS under hypoxia decreased significantly. On the other hand, non-adrenergic-non-cholinergic relaxation caused by EFS was unaffected by hypoxia. These observations suggest that hypoxia can modulate the responses of tracheal smooth muscle to acetylcholine, histamine and nerve stimulation.
To clarify the physiological role of estradiol 17-sulfate (ES) during pregnancy, experiments were conducted and the following results were obtained: (1) serum or urinary ES levels rose as a function of gestational age; (2) placental microsomes showed fairly high 2- and 4-hydroxylase activity for ES; and (3) the catechol products, 2- and 4-hydroxy-ES, had a strong inhibitory effect upon the in vitro production of lipid peroxides. These results suggest that ES acts as a precursor to the catechol metabolites which maintain normal gestation. This is coincident with the negative correlation of serum levels in ES and lipid peroxides observed in late pregnancy.
In a retrospective multi-center study, we investigated eighteen infants with unilateral cerebral infarctions confirmed by computed tomography (CT) scans. The initial symptoms were observed in all the patients between 0 and 3 days of age. Convulsions or apneic attacks were the initial symptoms in all but one. Only 4 patients had complicated obstetric histories and none showed polycythemia or electrolyte abnormalities. All of the initial CT scans revealed unilaterally localized hypodense areas. In 10, the initial CT scans were performed within 24 hours after the clinical onset. In 16, the lesions were within the territory of the middle cerebral artery, 9 of which also involved the cortico-spinal tract (CST). In the remaining 2 patients, the lesions were located within the territory of the posterior cerebral artery. None of the 9 patients without CST involvement developed hemiplegia, whereas 5 (56%) of the 9 with CST involvement had hemiplegia, which is a fairly low incidence compared with that in adult cases. This difference was thought to be related to neonatal brain plasticity.
We examined the effects of misonidazole (MISO) and recombinant human tumour necrosis factor (rh-TNF) on tumour blood flow in mice given hyperthermic treatments. MISO (500 mg kg-1) or rh-TNF (6 x 10(4) unit kg-1) was administered intraperitoneally (i.p.) prior to hyperthermia to nude mice bearing a xenoplanted human gastric cancer and tumour blood flow was measured by a hydrogen diffusion method based on polarographic determinations. MISO plus hyperthermia produced a temperature-dependent decrease in blood flow and, at 43.5 degrees C, the flow decreased to 15-30% of control and remained low for up to 24 h. Blood flow following rh-TNF plus hyperthermia was less than that at the same temperatures following MISO plus hyperthermia, and, at 43.5 degrees C, the flow decreased to 10-20% of control and remained low for up to 48 h. Tumour growth delay was closely related to the duration of the decrease in blood flow. Thus, the profound decrease in tumour blood flow following hyperthermia plus MISO or rh-TNF and the consequential tumour regression may well be of potential clinical significance.
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We recently reported that a unique B cell clone (B19-1d), specific for a cross-reactive idiotype (CRI) on MOPC104E myeloma protein (M104E), enhances Igh-restricted CRI+ antibody production. In this paper, we report the nucleotide sequences of immunoglobulin heavy chain variable regions (VH) of both M104E and B19-1d-derived hybridoma (HB19) antibodies. The sequence data revealed that both belong to the J558 germ line VH gene subfamily. Strikingly, not only the VH region, but also the leader sequences of M104E and HB19 are very similar to each other at 88% (VH) and 91% (leader) homology, but they use different D and J segments. The VH region sequence similarity is highest among the germ line VH gene sequences of the BALB/c J558 subfamily so far screened. Southern hybridization data, using 5'-noncoding regions of either M104E or HB19 genomic VH gene clones as probes, revealed that both VH genes are conserved in the M104E CRI producer strains of mice. Moreover, these probes show the restriction length polymorphism pattern of mouse VH genes in various strains. That the HB19 VH gene locates to the 5' upper arm of the M104E VH gene on the chromosome was suggested by Southern blot hybridization. Immunoglobulin VH gene restriction of idiotypic and antiidiotypic B-B cellular interaction is discussed from a molecular point of view.
Three nonchemotactic mutants (D54, Y14, and N74) of Campylobacter jejuni were isolated from wild-type strain FUM158432 by either the negative swarming or liquid gradient method with brucella broth as the attractive substance. Strains D54 and Y14 were isolated after mutagenesis with methyl methanesulfonate, and N74 was isolated from a nonmutagenized culture. These mutants all failed to swarm on a semisolid medium and did not show any chemotactic behavior in the hard-agar plus assay method for any of the chemicals which act as attractants for the wild-type strain. They had intact flagella and were actively motile. Swimming behavior examined by a video tracking technique showed that the mutants swim only straight, without any tumbling. When suckling mice were challenged orally with approximately 10(5) CFU of these mutant strains, all of the mutants were cleared from the intestinal tract by 48 h. In contrast, the wild-type strain colonized the intestinal tracts of all mice challenged with 10(2) CFU. We concluded that chemotactic movement is important for colonization of the intestinal tract of suckling mice by C. jejuni.
Campylobacter fetus strains may be of serotype A or B, a property associated with lipopolysaccharide (LPS) structure. Wild-type C. fetus strains contain surface array proteins (S-layer proteins) that may be extracted in water and that are critical for virulence. To explore the relationship of S-layer proteins to other surface components, we reattached S-layer proteins onto S- template cells generated by spontaneous mutation or by serial extractions of S+ cells with water. Reattachment occurred in the presence of divalent (Ba2+, Ca2+, Co2+, and Mg2+) but not monovalent (H+, NH4+, Na+, K+) or trivalent (Fe3+) cations. The 98-, 125-, 127-, and 149-kDa S-layer proteins isolated from strains containing type A LPS (type A S-layer protein) all reattached to S- template cells containing type A LPS (type A cells) but not to type B cells. The 98-kDa type B S-layer protein reattached to SAP- type B cells but not to type A cells. Recombinant 98-kDa type A S-layer protein and its truncated amino-terminal 65- and 50-kDa segments expressed in Escherichia coli retained the full and specific determinants for attachment. S-layer protein and purified homologous but not heterologous LPS in the presence of calcium produced insoluble complexes. By quantitative enzyme-linked immunosorbent assay, the S-layer protein copy number per C. fetus cell was determined to be approximately 10(5). In conclusion, C. fetus cells are encapsulated by a large number of S-layer protein molecules which may be specifically attached through the N-terminal half of the molecule to LPS in the presence of divalent cations.
Fiber type differentiation as revealed by myosin ATPase activities and the immunological analysis of myosin light chains (MLC) by the Western blotting method were done on the postnatal rat soleus and extensor digitorum longus (EDL) muscles. In the soleus, type 1 (slow-twitch) muscle fibers gradually increase in percentage after postnatal day 10, and, in the EDL, the differentiation of type 2A and 2B (fast-twitch) muscle fibers is also pronounced between postnatal days 10 and 15. The present immunological analysis of MLC indicates that the antigenicity of Lc1S becomes more intense with a rapid decrease in antigenicity of Lc2F from postnatal day 7 in the soleus, while the antigenicity of Lc1F becomes noticeable during the same period in the EDL. These results suggest that the differentiation of slow-twitch fibers is mainly due to that of Lc1S in the soleus and the differentiation of fast-twitch fibers is mainly due to that of Lc1F in the EDL.
The immunocytochemical localization of alpha-fetoprotein (AFP)-producing cells was observed in pre- and postnatal and carbon tetrachloride (CCl4)-treated rat livers in comparison with that of albumin (ALB)-producing cells. According to immunoblotting data, considerable numbers of AFP-positive hepatocytes were observed in the differentiating liver between prenatal day 19 and postnatal day 0 (6 h after birth). Analyses by serial section profiles of these cells revealed that certain AFP-positive hepatocytes are also stained with ALB antiserum. Immunoelectron microscopy of the AFP-producing cells revealed that immunoreactive gold particles are preferentially localized in rough endoplasmic cisternae, Golgi apparatus and Golgi-derived vesicles near the cell surface. In addition, the release of the content of the Golgi-derived vesicles into the differentiating bile canaliculi as well as into the space of Disse by exocytosis is apparent. In CCl4-treated rat liver, immunoreactions to AFP are localized exclusively in newly formed hepatocytes of the regenerative tissue. These AFP-positive cells have not established the hepatic cell cords, and the adjacent ones are conjugated to each other mainly by simple attachment devices as in the case of those in pre- and postnatal rat liver.
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We studied cellular resistance to copper of plant cells Polygonum cuspidatum. When callus of P. cuspidatum was incubated on medium containing 100 microM cupric sulfate, the callus grew as well as the control callus did. The copper content of the callus, however, was elevated to a similar level of the medium. When cell extracts of callus exposed to 100 microM cupric sulfate were fractionated by gel filtration chromatography, a specific copper peak was eluted at the region of molecular weights between 4000 and 1000. Since an appearance of the copper-containing materials was inhibited by buthionine sulfoximine and the partially purified copper-containing materials contained only three amino acids: glutamic acid, glycine and cystine, the materials were supposed to be gamma-glutamyl peptides phytochelatins. Callus of P. cuspidatum synthesized phytochelatins from 50 microM cupric sulfate and maximally at 100-150 microM cupric sulfate. When induction of phytochelatins by another heavy metal, zinc, was analyzed, the callus, however, did not synthesize phytochelatins on exposure to zinc sulfate up to 1 mM. These findings suggested that phytochelatins were required for resistance to copper but probably not to zinc in the plant cells.
Acid phosphatase isozyme was highly purified from rat liver mitochondrial fraction. The enzyme showed an isoelectric point value of above 9.5 on isoelectric focusing, and the apparent molecular weight was estimated to be 32000 by Sephadex G-100 gel filtration or 16000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme catalyzed the hydrolysis of adenosine 5'-triphosphate, adenosine 5'-diphosphate, thiamine pyrophosphate, inorganic pyrophosphate, and phosphoprotein such as casein and phosvitin, but not of several phosphomonoesters, except for p-nitrophenyl phosphate and o-phosphotyrosine. The enzyme was not inhibited by L-(+)-tartrate, and was significantly activated by Fe2+ and reducing agents such as ascorbic acid, L-cysteine,and dithiothreitol. The enzyme was found to be distributed in various rat tissues including liver, spleen, kidney, small intestine, lung, stomach, brain and heart, but not in skeletal muscle.
A 48-year-old woman was admitted to our hospital because of proteinuria associated with persistent hypocomplementemia. Intravenous pyelography indicated the presence of horseshoe kidney without other abnormalities. Hypocomplementemia was caused by cold activation of complement. There were some findings suggestive of chronic liver disease (positive HCV antibody, hypergammaglobulinemia, low cholinesterase, etc.). Percutaneous renal biopsy showed the features of multiple evolutional phases of membranous glomerulonephritis.
Extracellular proteolysis is hypothesized to be the major cause of pulmonary emphysema and oxygen-derived free radicals and neutrophil elastase are thought to play an important role in its pathogenesis. In this study, peripheral polymorphonuclear leukocytes (PMNs) obtained from 16 patients with emphysema generated a significantly larger amount of superoxide and elastase activity than those obtained from normal controls. A significant correlation was observed between elastase activity and superoxide release. In addition, the superoxide release showed a negative correlation with the disease duration. The superoxide release appeared to correlated with a decline of FEV1.0 over the course of several years in 8 patients. It seems likely that activated PMNs play an important role in the development of pulmonary emphysema.
The activity of dihydropyrimidine dehydrogenase, which is the rate-limiting enzyme in the catabolism of pyrimidine, in livers of 5-day-old rats increased 48 h after glucocorticoid injection. The increase in the activity of dihydropyrimidine dehydrogenase by glucocorticoid administration and by aging did not decrease the uridine, uracil and sigma UMP (the sum of acid-soluble uracil 5'-nucleotides) pool in liver. The increase of liver uracil by a uridine diet not increase dihydropyrimidine dehydrogenase activity. The increase of liver uracil did not increase dihydropyrimidine dehydrogenase activity. However, dihydropyrimidine dehydrogenase activity which increased after glucocorticoid treatment increased the pyrimidine-degradation rate in rat livers and hepatocytes. Pyrimidine catabolism pathway in liver may play an important role in degradation of dietary pyrimidines and pyrimidines which are administered in the form of medicines as 5-fluorouridine.