Use of L-prolyl-L-leucylglycinamide (MIF-1) for the high-performance liquid chromatographic determination of proline iminopeptidase activity in rat liver.
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Aminopeptidases↗
Biomedical subjects
M Harada
Publications and source records attributed to M Harada.
Reversible bone marrow hypoplasia induced by alcohol.
A 51-year-old man developed severe pancytopenia with bone marrow hypoplasia after consuming excessive amounts of alcohol for many years. After avoiding alcohol and eating normally for about 10 days, his blood cell counts promptly recovered to near-normal levels. Hematologic remission had lasted for 7 months until he began to drink alcohol excessively again, leading to a relapse of pancytopenia with marrow hypoplasia. His blood cell counts attained near-normal levels again after abstaining from alcohol for about a month. He developed thrombocytopenia following moderate ingestion of alcohol 7 months later, but he never developed severe pancytopenia after limiting alcohol ingestion. When bone marrow mononuclear cells from the patient and normal volunteers were cultured in the presence of ethanol, CFU-GM-derived colony formation of the patient was inhibited by much lower concentrations of ethanol than that of normal volunteers. The clinical course of the patient and the greater sensitivity of the patient's CFU-GM to ethanol toxicities indicate that massive intake of alcohol was responsible for bone marrow hypoplasia observed in this patient.
Alcohol Drinking↗
Simultaneous occurrence of myelomonocytic leukemia and multiple myeloma: involvement of common leukemic progenitors and their developmental abnormality of "lineage infidelity".
We investigated the origin of leukemic progenitors in a case of the simultaneous occurrence of myelomonocytic leukemia and multiple myeloma (IgG-kappa). At presentation, myeloperoxidase and nonspecific esterase-positive myelomonocytic cells had proliferated up to 12.2 x 10(9)/liter in the peripheral blood. Bone marrow cell differentials revealed the coexistence of myelomonocytic cells (30%) and atypical plasmacytoid cells (26%). Myelomonocytic cells in peripheral blood expressed both myeloid antigens (CD11b, CD13, CD14, CD15, CD33) and T/B-lymphoid antigens (CD2, CD4, CD5, CD7, CD10, PCA-1). Bone marrow mononuclear cells (BMMC) could be divided into PCA-1 strongly positive and PCA-1 weakly positive populations, which were considered to represent myeloma cells and myelomonocytic cells, respectively; the former were CD2-positive (CD2+), CD14-, and CD15-, whereas the latter were CD2+, CD14+, and CD15+. Immunohistochemical analysis revealed that, in addition to plasmacytoid cells, a minority of myelomonocytic cells showed a positive reaction for IgG staining, and production of IgG was observed in the culture supernatant of CD14+ myelomonocytic cells in peripheral blood. Southern blot analysis revealed the presence of two identical rearrangement bands of immunoglobulin heavy chain gene in both BMMC containing myeloma cells and myelomonocytic cells and CD14+ myelomonocytic cells in peripheral blood. In a long-term methylcellulose assay, peripheral blood mononuclear cells produced large compact colonies consisting of macrophages and IgG+ plasmacytoid cells (M phi/P colonies), while BMMC produced a different type of colonies consisting of CD14+ myelomonoblasts, macrophages, and IgG+ plasma cells (Mb/M phi/P colonies) in addition to M phi/P colonies. Recloning experiments showed that primary Mb/M phi/P colonies gave rise to both secondary M phi/P and Mb/M phi/P colonies. These observations strongly suggest that common leukemic progenitors provide both myeloma and myelomonocytic leukemia cells, and the mechanism of "lineage infidelity" is probably involved in the development of their "bilineal" differentiation.
Antigens, CD↗
A new method for the evaluation of the liver injury by 19F MRS of 5-fluorouracil.
An investigation was made of 5-fluorouracil metabolism in rat liver by 19F MRS. Fluoronucleotide synthesis increased markedly with liver injury and accelerated with uracil treatment, indicating that 19F MRS may serve as a new method for evaluating liver viability.
Animals↗
Gene expression of cytokines suppressing hematopoietic progenitor cells in lymphoid malignancies.
The expression of cytokine genes for tumor necrosis factor alpha (TNF alpha), lymphotoxin and transforming growth factor beta (TGF beta), all of which are known to suppress normal hematopoiesis, was investigated in 32 patients with lymphoid malignancies using Northern blot analysis. Messenger RNA (mRNA) for TNF alpha, lymphotoxin and TGF beta was detected in 9 cases, 2 cases and 7 cases, respectively. When the relationship between cytokine gene expression and surface phenotype was analyzed, the expression of CD19 correlated significantly with expression of the TNF alpha gene (P less than 0.05). This suggests that B cell malignancies are likely to produce TNF alpha. When the hematological parameters of patients expressing and not expressing the gene were compared, the expression of TNF alpha mRNA was found to correlate with more profound anemia in acute lymphoblastic leukemia (P less than 0.05). Both granulocyte and platelet counts were lower in patients expressing TNF alpha mRNA; however, the decreases were not significant. Neither lymphotoxin nor TGF beta gene expression correlated significantly with any hematological parameter.
Adolescent↗
Differential effect of a PAF antagonist CV-3988 on active and passive anaphylactic shock in various mouse strains.
To define the role of platelet-activating factor (PAF) in anaphylactic shock in the mouse, the suppressive effect of CV-3988, a PAF antagonist, on active and passive anaphylactic shock was studied. Various mouse strains treated or not treated with Bordetella pertussis (B. pertussis) were used. We found that the effect of CV-3988 on anaphylactic shock in the mice that were actively sensitized with bovine serum albumin plus B. pertussis differed markedly according to mouse strain. CV-3988 suppressed the anaphylactic shock in C3H/He and CBA/JN mice at a low dose of 3 mg/kg, whereas antagonists to other mediators such as histamine, serotonin, thromboxane A2 and leukotrienes did not show a suppressive effect. This suggests that PAF plays a major role in anaphylactic shock in these strains. On the other hand, CV-3988 did not suppress active anaphylactic shock in cataract Shionogi (CTS), NOD and DS strains even at a high dose of 30 mg/kg, which could be interpreted to suggest that PAF is not active in these strains. However, this possibility was ruled out based on the similar results obtained in passive anaphylactic shock and PAF-induced shock in these mice. Passive anaphylactic shock in CTS mice mediated by IgG1 antibody was markedly suppressed by CV-3988 but not at all by antagonists to other mediators. Furthermore, the suppressive action of CV-3988 against passive anaphylactic shock, and PAF-induced shock was greatly attenuated when the mice were pretreated with B. pertussis. From these results, the conclusion can be drawn that PAF is the main mediator of active and passive anaphylactic shock in the mouse in general, even though the effect of CV-3988 differs depending on the mouse strain and on whether or not B. pertussis treatment is used.
Anaphylaxis↗
Involvement of activated polymorphonuclear leukocytes in galactosamine-induced hepatic injury in rats.
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Animals↗
Possible mechanism of the preventive effect of BCG against diabetes mellitus in NOD mouse. I. Generation of suppressor macrophages in spleen cells of BCG-vaccinated mice.
With the aim of clarifying the mechanism of the suppressive action of BCG against insulitis and overt diabetes in NOD mice, we studied the effects of BCG on spleen cell populations and on the in vitro immune responses of spleen cells. The spleen cells of BCG-vaccinated mice showed much lower responsiveness to various mitogens such as Con A, PHA, PWM, and LPS than those of saline-treated mice. Low responsiveness to alloantigens was also observed. Flow cytometric analysis of the spleen cells revealed that Mac-1+ and Mac-2+ cells had increased while T and B cells had decreased in the BCG-vaccinated mice compared with the saline-treated mice at the time when the maximum level of inhibition of mitogen responses of BCG-vaccinated mice was observed. This suggests that the decreased in vitro immune response was due to the increase in macrophages which suppress lymphocyte functions. Support for this interpretation comes from the following two findings: (1) the restoration of mitogen responses of spleen cells when macrophages were eliminated by plastic adhesion or FACS sorting and (2) resuppression of PHA and Con A responses of plastic-nonadherent spleen cells by addition of adherent cells or flow cytometrically sorted Mac-1+ cells obtained from BCG-vaccinated mice. These results indicate the generation of suppressor macrophages after BCG vaccination and suggest that these macrophages prevent the autoimmune pathogenesis leading to diabetes in NOD mice.
Animals↗
Possible mechanism of the preventive effect of BCG against diabetes mellitus in NOD mouse. II. Suppression of pathogenesis by macrophage transfer from BCG-vaccinated mice.
Our previous reports showed that a single injection of live BCG, one of the biological response modifiers, prevents insulitis and overt diabetes in NOD mice and that the suppression could be due to the generation of some type of suppressor cells in the BCG-treated mice. Furthermore, a more recent study has revealed that macrophages suppressive against a variety of lymphocyte functions can be induced by BCG, which suggests that these macrophages are involved in the suppression of the pathogenesis. To obtain valid evidence for this speculation, the effects of transfer of macrophage and T-cell fractions on the pathogenesis were examined in the present study. Transfer of macrophage-enriched spleen cell fraction harvested from the BCG-treated females to young females abolished the occurrence of spontaneous diabetes up to the age of 25 to 30 weeks. Also, macrophage transfer prevented the progress of insulitis. In contrast, transfer of a T-cell-enriched fraction did not suppress insulitis and overt diabetes. From these results, it could be concluded that the suppression of the autoimmune pathogenesis of diabetes by BCG is due to the generation of suppressor macrophages.
Animals↗
Increased uptake of bromodeoxyuridine by hepatocytes from early stage of primary biliary cirrhosis.
The relationship between DNA synthesis activities of hepatocytes in biopsied specimens and liver volume was studied in various stages of primary biliary cirrhosis using an in vitro bromodeoxyuridine (a thymidine analogue)-anti-bromodeoxyuridine reaction and computed tomography. The mean bromodeoxyuridine (+/- SE) labeling index for 10 patients in an early histological stage (stage I, 4, and stage II, 6, 3.4% +/- 0.4%) of primary biliary cirrhosis was 17 times that for 6 control subjects (0.2% +/- 0.1%, P less than 0.001), and was significantly higher than that for 19 female patients with chronic aggressive hepatitis (0.9% +/- 0.2%, P less than 0.001), 14 compensated cirrhotic patients of viral origin (all female, 1.1% +/- 0.3%, P less than 0.01), and 5 patients with stage III primary biliary cirrhosis (0.5% +/- 0.1%, P less than 0.001). The mean (+/- SE) liver volume in the early stage of primary biliary cirrhosis (1225 +/- 40 cm3) was about 1.5 times that in control subjects (835 +/- 42 cm3, P less than 0.001). These results suggest that liver volume has already become large in the early stage of primary biliary cirrhosis perhaps because of markedly increased DNA synthesis in hepatocytes.
Adult↗
Hyperprolactinemia in multiple sclerosis.
In order to clarify endocrine abnormalities due to hypothalamic involvement in multiple sclerosis (MS), serum prolactin levels were measured in 27 patients with MS and 22 healthy subjects. The presence of hypothalamic lesions was also studied by magnetic resonance imaging (MRI). Serum prolactin levels were found to be significantly higher in MS patients than in healthy controls in both sexes. Although only one patient had galactorrhea, one-third of the MS patients had mild to moderate hyperprolactinemia, which was a 4-13-fold increase over the mean value of healthy subjects. The results of thyrotropin-releasing hormone, sulpiride, L-DOPA and bromocriptine loading tests suggested a hypothalamic dysfunction, rather than pituitary prolactinoma in MS patients. Four of eight patients with hyperprolactinema had diencephalic hypothalamic lesion(s) contiguous with the third ventricle on the brain MRI, while none of the normoprolactinemic patients had any lesions in the diencephalon. All relapsing-remitting patients with hyperprolactinemia showed a rise in prolactin levels in the acute stage of the relapse and a decrease during the recovering stage and the following remission phase. Our findings suggest that latent hyperprolactinemia due to hypothalamic dysfunction occurs frequently in MS patients in relapse. The increase of serum prolactin is considered to be a sensitive indicator for hypothalamic lesions in MS.
Adult↗
Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in prenatal stage on the dopamine system in the postnatal mouse brain.
A dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP), administered to a pregnant female was found to affect postnatally the catecholamine metabolism of the pups. MPTP (5 mg/kg body weight/day) was administered to pregnant C57 Black BYA mice daily for 7 days between the 12th and 18th day of gestation. Dopamine levels and tyrosine hydroxylase (TH) activity were measured in the whole brain from the pups sacrificed after birth. In MPTP-treated pups at 7 days of age, TH total activity (TH activity/brain) did not change (92% of the control value), while TH specific activity (TH activity/mg protein) was increased to 163% of that in control mice. Thus, TH homospecific activity (TH activity/mg TH protein) doubled compared to the control mice. At 28 days of age, both the total activity and the specific activity of TH in the brains of postnatal mice were reduced to 50% and 78% of the control, respectively. Dopamine concentration in the striatum was also reduced significantly. Reduction in the TH activity and dopamine concentration were also observed at the age of 12 weeks. These data suggest that the prenatal exposure to MPTP induced a prolonged reduction of TH activity in the brains of mice with a transient increase of TH homospecific activity during the postnatal period.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Distribution and sources of polycyclic aromatic hydrocarbons (PAHs) in street dust from the Tokyo Metropolitan area.
Molecular distributions of polycyclic aromatic hydrocarbons (PAHs) in street dust samples collected from the Tokyo Metropolitan area were determined by capillary gas chromatography following HPLC fractionation. Three- to six-ring PAHs and sulfur-heterocyclics were detected. PAHs in the dusts were dominated by three and four unsubstituted ring systems with significant amounts of their alkyl homologues. PAHs were widely distributed in the streets, with concentrations (sigma COMB) of a few microgram/g dust. Automobile exhaust, asphalt, gasoline fuel, diesel fuel, tyre particles, automobile crankcase oils, and atmospheric fallout were also analysed. The PAH profile, especially the relative abundance of alkyl-PAHs and sulfur-containing heterocyclics, indicated that PAHs in the street dusts from roads carrying heavy traffic are mainly derived from automobile exhausts; dusts from residential areas have a more significant contribution from atmospheric fallout.
Chromatography, High Pressure Liquid↗
Primary structure and localization of a conserved immunogenic Plasmodium falciparum glutamate rich protein (GLURP) expressed in both the preerythrocytic and erythrocytic stages of the vertebrate life cycle.
A gene coding for a 220-kDa glutamate rich protein (GLURP), an exoantigen of Plasmodium falciparum, was isolated and its nucleotide sequence was determined. The deduced amino acid sequence contains 2 repeat regions. The sequence of one of these was shown to be conserved among geographically dispersed isolates, and a fusion protein containing that sequence was able to stimulate B- and T-cells. Antibodies against GLURP stained erythrocytic stages of the parasite as well as the hepatic stage as detected by electron microscopy.
Amino Acid Sequence↗
Induction and localization of Plasmodium falciparum stress proteins related to the heat shock protein 70 family.
Induction of heat shock-related stress proteins Pfhsp and Pfgrp, similar in sequence to hsp70 (heat shock protein) and grp78 (glucose-regulated protein), respectively, was studied in culture-derived parasite Plasmodium falciparum. Elevation in temperature from 26 degrees C to 37 degrees C and higher caused significant induction of Pfhsp with a moderate effect on the synthesis of Pfgrp also. Synthesis of Pfgrp, however, was not induced by partial glucose deprivation. On the contrary, lack of glucose in the medium resulted in cessation of protein synthesis in the parasites. Other known inducers of grp synthesis in mammalian cells, i.e., calcium ionophore A23187 and inhibitors of glycosylation (tunicamycin, 2-deoxy glucose) were also without any apparent effect on the synthesis of Pfgrp. Heat shock-induced responses were transient in nature: removal of stress caused repression of these responses. The effect of glucose deprivation was only partially reversible with better recovery if parasites were subjected to glucose starvation at 26 degrees C than at 37 degrees C. Northern blot analysis and in vitro translation of mRNA revealed a parallel increase in the levels of mRNA for Pfhsp upon heat shock. Immuno-gold electron microscopy with cultured parasites revealed nuclear location of Pfhsp and primarily cytoplasmic (probably endoplasmic reticulum) location of Pfgrp. These findings suggest that SDEL (carboxy terminal sequence of Pfgrp) might play a similar role in the cellular localization of Pfgrp as does the sequence KDEL in mammalian cells and HDEL in yeast.
Amino Acid Sequence↗
Autoreactive T cells from normal mice recognize mycobacterial 65 kd heat-shock protein from Mycobacterium bovis.
We established a TCR V beta 6+ CD4+ autoreactive T cell line from lymph node cells of unprimed BALB/c mice bred in a specific pathogen-free condition. The T cell line proliferated in the presence of irradiated spleen cells expressing MHC class II I-Ad and/or I-Ed molecules. The proliferative response of the autoreactive T cell line was significantly enhanced in response to 65 kd heat-shock protein (hsp) from Mycobacterium bovis, a member of the hsp60 family, which is highly conserved in both prokaryotes and eukaryotes. Our results suggest that the autoreactive T cells in normal mice may recognize endogenous peptides of self-hsp60 bound to MHC class II gene products and are cross-reactive to mycobacterial 65 kd hsp. The autoreactive hsp-specific T cells may therefore play an important role in the immune surveillance against invasion of various pathogens and tumors by recognizing infected and transformed autologous cells that express high levels of endogenous hsp60.
Animals↗
Immunologic reactions of human recipients to repeated exposures to Albunex microspheres.
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Albumins↗
Molecular analysis of rice dwarf phytoreovirus segment S11 corresponding to wound tumour phytoreovirus segment S12.
The complete nucleotide sequence of rice dwarf phytoreovirus (RDV) genome segment S11 was determined. S11 is 1067 nucleotides long. There is an inverted repeat of 10 bp adjacent to the conserved 5'-terminal hexanucleotide (5' GGUAAA 3') and 3'-terminal tetranucleotide (5' UAGU 3') sequences. A single large open reading frame found in the plus strand of S11 begins with the first AUG codon (bases 6 to 8) and extends for 567 bases. Evolutionary relatedness between RDV S11 and wound tumour phytoreovirus S12 based on amino acid sequence similarity (25.8%) was found. In addition to the first AUG triplet, RDV S11 possesses a second in-phase AUG triplet (positions 30 to 32) nearby, which conforms to the Kozak consensus sequence. Two forms of the protein were identified by using an in vitro transcription and translation system in which a tailored full-length cDNA was the initial template. The abolition of the first AUG codon by site-directed mutagenesis resulted in disappearance of the larger translation product. These results strongly suggest that the two products are translated from the first and second AUG codons. Whether the two proteins are expressed in vivo is at present unclear.
Amino Acid Sequence↗