Biomedical subjects

M Shoji

Publications and source records attributed to M Shoji.

At least 181 records · Page 10Linked to original sources

PubMed1995

Alpha 1-antichymotrypsin level in cerebrospinal fluid is closely associated with late onset Alzheimer's disease.

The levels of alpha 1-antichymotrypsin (ACT) in cerebrospinal fluid (CSF) from 66 sporadic Alzheimer's disease (AD) patients and 54 normal controls were measured by enzyme immunoassay and compared. There was no correlation (r = 0.259, n = 54) between the ACT level and normal aging. The levels of ACT were significantly higher in the total AD group (p < 0.01) than in the normal control group. Dividing AD patients into early onset AD (n = 27) and late onset AD groups (n = 39), the mean level of CSF ACT in the late onset AD group was significantly higher than that in the normal control group (p < 0.001) and that in the early onset AD group (p < 0.01). Thus, the level of ACT in CSF is closely associated with late onset AD.

Adolescent↗

PubMed1995

Establishment and characterization of a new Ph1-positive chronic myeloid leukemia cell line MC3 with trilineage phenotype and an altered p53 gene.

A new Ph1-positive leukemic cell line (MC3) expressing the P210bcr/abl oncoprotein was established from a patient with CML in blast crisis. The MC3 cells showed the trilineage phenotype of myeloid, lymphoid (CD19) and megakaryocytoid lineages, and had a proliferative response to rhIL-1 and rhIL-3 in the serum-free culture. These results and the expression of CD34 indicated that the MC3 cells have characteristics of hematopoietic progenitor cells. Recently, it has been documented that alterations of the p53 gene in leukemic cells are frequently detected during the blast crisis of CML. The MC3 cells contained the altered p53 gene. In addition, the original leukemic cells showed the point-mutational activation of the N-ras gene and an additional chromosomal abnormality inv(3q), but the MC3 cells contained no such abnormalities, indicating that not all of the original leukemic cells had these abnormalities. Thus, the MC3 cell line may provide several insights into investigations of the blast crisis in CML as well as hematopoietic progenitor cells.

3T3 Cells↗

PubMed1995

Immunocytochemical detection of lung cancer cells with monoclonal antibodies to 14-3-3 proteins.

Murine monoclonal antibodies were raised against 14-3-3 proteins, the antigen of human monoclonal antibody AE6F4 which had been shown potentially useful for the immunochemical diagnosis of lung cancer via sputum cytology. Enzyme-linked immunosorbent assays of the murine anti-14-3-3 monoclonal antibodies with isolated bovine brain 14-3-3 isoforms showed that the antibodies were classified into four different profiles of isoform reactivity. The comparison of 14-3-3 isoform and lung cancer tissue on the reactivity with murine monoclonal antibodies indicated that beta isoform can be responsible for cancer recognition, whereas human monoclonal antibody AE6F4 showed preferential binding to zeta isoform. No murine monoclonal antibody of the same isoform specificity as human monoclonal antibody AE6F4 was obtained. Since murine monoclonal antibodies with different isoform specificities could immunostain lung cancer cells in sputum successfully, the combination use of murine monoclonal anti-14-3-3 antibodies with human monoclonal antibody AE6F4 is potentially useful for facilitating the sputum cytodiagnosis of lung cancer.

14-3-3 Proteins↗

PubMed1994

Alternative splicing of the mRNA encoding baboon glycoprotein receptor GPIIb.

The cloning and characterization of cDNAs encoding the cell-surface-specific integrin receptors of baboon platelets has been undertaken to provide species-specific probes. These will be used to investigate the expression and distribution of these receptors among primate species. Clones GPIIb-16 and GPIIb-3, encoding portions of the baboon glycoprotein GPIIb, were isolated from a cDNA library derived from baboon platelet mRNA. GPIIb-3 includes an insert of 43 bp, when compared to GPIIb-16 or human GPIIb. This insert is the result of alternative processing of mRNA. The probable origin of the inserted bases is the 3' end of the intron preceeding exon 28 of the gene. A different product of alternative splicing has been reported in this same region of the human GPIIb sequence, suggesting that this location is susceptible to wobble in the intron-exon junctions. The projected shift in the reading frame of the baboon GPIIb-3 cDNA would give a radically altered C terminus of the deduced amino-acid sequence, and the possibility of a novel functional peptide on the platelet surface.

Alternative Splicing↗

PubMed1994

The role of GABA in the central regulation of AVP and ANP release and blood pressure due to angiotensin and carbachol, and central GABA release due to blood pressure changes.

To assess whether GABA given intracerebroventricularly (i.c.v.) affects vasopressin (AVP) and atrial natriuretic peptide (ANP) release and changes in blood pressure in response to i.c.v. angiotensin (AT II) and carbachol (CB), or whether changes in blood pressure affect GABA release in the brain, experiments were carried out. In experiment I (Ex I), GABA (100 micrograms) with AT II (50 ng) or CB (25 ng) was i.c.v. administered in conscious rats (n = 12). The same dose of AT II or CB alone also was administered without GABA (n = 12). In experiment II (Ex II), AT II (100 ng/kg per min) or nitropuruside (NP, 10 micrograms/kg per min) was intravenously (i.v.) infused and GABA release in the area adjacent to the paraventricular nucleus was determined, using the microdialysis method, in conscious rats (n = 12). In the experiments, mean arterial blood pressure (MABP), heart rate (HR), plasma AVP and/or ANP and plasma Na+ and K+ levels were measured. In Ex I, i.c.v. AT II increased plasma AVP and MABP without changes in HR and plasma ANP, but i.c.v. GABA never affected these responses. Icv CB also increased plasma AVP and MABP with decreased HR, but did not affect plasma ANP. Icv GABA abolished bradycardiac responses, but did not affect the others. In Ex II, the pressor response to i.v. AT II increased GABA release without apparent decreases in plasma AVP. However, the depressor response to NP produced decreases in GABA release with increased plasma AVP. These results shows that i.c.v. GABA did not affect AVP and pressor responses to i.c.v. AT II and CB, but changes in blood pressure modulates GABA release in the brain with changes in plasma AVP.

Angiotensin II↗

PubMed1994

Differential inhibition of eukaryotic DNA polymerases by halenaquinol sulfate, a p-hydroquinone sulfate obtained from a marine sponge.

Halenaquinol sulfate, a p-hydroquinone sulfate obtained from a marine sponge, inhibited the activity of eukaryotic DNA polymerases in varying degrees; the Ki values for DNA polymerases, alpha, beta, delta and epsilon were 1.3, 80, 17.5 and 2.0 microM, respectively, whereas it was less effective against E. coli DNA polymerase I. The inhibition occurred competitively with each of dATP and dTTP, but non-competitively with dCTP, dGTP and the template DNA. Thus, halenaquinol sulfate is demonstrated to be a potential inhibitor of DNA polymerases alpha and epsilon, and be a useful tool for analyzing the dNTP binding sites of DNA polymerases.

Animals↗

PubMed1994

Sphingosine inhibits the synthesis of RNA primers by primase in vitro.

We have previously shown the presence of sphingomyelin and sphingomyelinase in cell nuclei, suggesting that they may play a role in the intranuclear production of sphingosine, a potent bioactive molecule modulating diverse cellular functions. In the present study, the direct effects of sphingosine (C18:1) on the activity of DNA replication/repair polymerases were studied in vitro. Sphingosine had no effect on DNA polymerases alpha and beta and slightly inhibited DNA polymerases gamma, delta, and epsilon. In contrast, sphingosine strongly inhibited the activity of primase in a dose-dependent manner. On the other hand, dihydrosphingosine (C18:0), glycolipids, sphingomyelin, and ceramide had no effect on primase activity. Sphingosine equally inhibited the activity of primase complexed with DNA polymerase alpha, as well as its free form, with a Ki value of 4 microM. A gel-retardation analysis showed that the binding of primase with 32P-labeled template DNA was suppressed by sphingosine. Inhibition by sphingosine was competitive with the DNA template, but not with the substrate NTPs. After product analysis, a dose-dependent decrease in the amount of RNA primer products, consisting mainly of 10- and 11-mers, was observed in the presence of sphingosine, indicating that it inhibits the synthesis of RNA primers by primase. Sphingosine, however, had no effect on T7 RNA polymerase.

Animals↗

PubMed1994

Sulfate- and sialic acid-containing glycolipids inhibit DNA polymerase alpha activity.

The effects of various glycolipids on the activity of immunoaffinity-purified calf thymus DNA polymerase alpha were studied in vitro. Preincubation with sialic acid-containing glycolipids, such as sialosylparagloboside (SPG), GM3, GM1, and GD1a, and sulfatide (cerebroside sulfate ester, CSE) dose-dependently inhibited the activity of DNA polymerase alpha, while other glycolipids, as well as free sphingosine and ceramide did not. About 50% inhibition was achieved by preincubating the enzyme with 2.5 microM of CSE, 50 microM of SPG or GM3, and 80 microM of GM1. Inhibition was noncompetitive with both the DNA template and the substrate dTTP, as well as with the other dNTPs. Since the inhibition was largely reversed by the addition of 0.05% Nonidet P40, these glycolipids may interact with the hydrophobic region of the enzyme protein. Apparently, the sulfate moiety in CSE and the sialic acid moiety in gangliosides were essential for the inhibition since neither neutral glycolipids (i.e., glucosylceramide, galactosylceramide, lactosylceramide) nor asialo-gangliosides (GA1 and GA2) showed any inhibitory effect. Furthermore, the ceramide backbone was also found to be necessary for maximal inhibition since the inhibition was largely abolished by substituting the lipid backbone with cholesterol. Increasing the number of sialic acid moieties per molecule further enhanced the inhibition, while elongating the sugar chain diminished it. It was clearly shown that the N-acetyl residue of the sialic acid moiety is particularly essential for inhibition by both SPG and GM3 because the loss of this residue or substitution with a glycolyl residue completely negated their inhibitory effect on DNA polymerase alpha activity.

Animals↗

PubMed1994

Distribution of 111In- and 125I-labeled monoclonal antibody 17-1A in mice bearing xenografts of human pancreatic carcinoma HuP-T4.

BACKGROUND: The prognosis of pancreatic adenocarcinoma still remains poor because of the lack of reliable diagnostic tests for early stages of the disease. Monoclonal antibody 17-1A (MoAb 17-1A) has been studied extensively, and the antigen recognized by MoAb 17-1A is expressed by adenocarcinomas of the pancreas and stomach, as well as other normal and malignant epithelial tissues. The potential of MoAb 17-1A was investigated for its ability to detect pancreatic carcinomas. The use of MoAb 17-1A in treatment also was studied. METHODS: Immunoreactivity of MoAb 17-1A with human pancreatic carcinoma cell line HuP-T4 was examined histochemically by the avidin-biotinylated enzyme complex method. MoAb 17-1A was labeled with 125I by the Iodogen method and 111In using either diethylenetriaminepentaacetic anhydride (cDTPA) or 1-(p-benzyldiazonium) diethylenetriaminepentaacetic acid (aDTPA). After injection in nude mice bearing HuP-T4 xenografts, the biodistribution of 111In- and 125I-labeled MoAb 17-1A was examined at various time points. RESULTS: Positive staining of MoAb 17-1A was noted for HuP-T4 cells. A statistically significant (P < 0.01) greater tumor uptake was observed at 3 days after intravenous injection of 125I-labeled MoAb 17-1A when compared with 125I-labeled nonspecific immunoglobulin G. 125I- and 111In-labeled MoAb 17-1A was concentrated in HuP-T4 carcinoma 1.9-4.8 times higher than in the spleen, heart, liver, and pancreas. CONCLUSIONS: MoAb 17-1A was found to bind selectively to human pancreatic carcinoma HuP-T4. Tumor exhibited higher uptake of radiolabeled MoAb 17-1A compared with adjacent normal tissues. These results suggest that MoAb 17-1A may be applicable to the radioimmunodetection and radioimmunotherapy of pancreatic adenocarcinomas.

Absorption↗

PubMed1994

Amyloid beta protein levels in cerebrospinal fluid are elevated in early-onset Alzheimer's disease.

The 4-kd amyloid beta protein (A beta) deposited as amyloid in Alzheimer's disease (AD) is produced and released by normal proteolytic processing of the amyloid beta protein precursor (beta APP) and is readily detected in cerebrospinal fluid (CSF). Here, we present the levels of A beta in CSF from a total of 95 subjects, including 38 patients with AD, 14 with early-onset AD and 24 with late-onset AD, 25 normal control subjects, and 32 patients with other neurological diseases. The level of A beta decreased with normal aging, and there was a significant elevation in the level of A beta in the CSF of early-onset AD patients (4.14 +/- 1.37 pmol/ml, p < 0.01). Neither Mini-Mental State nor Functional Assessment Staging were correlated with the amount of A beta in the CSF. The A beta/secreted form of beta APP ratio was elevated, but the level of alpha 1-antichymotrypsin in the CSF did not correlate with the level of CSF A beta in early-onset AD patients. Thus, the level of A beta in the CSF is elevated in early-onset AD patients and is suggested to be correlated with the pathology in the brain that characterizes AD.

Adult↗

PubMed1994

Effect of herbimycin A, an inhibitor of tyrosine kinase, on protein tyrosine kinase activity and phosphotyrosyl proteins of Ph1-positive leukemia cells.

Herbimycin A, a benzoquinonoid anasamycin antibiotic, preferentially inhibited the in vitro growth of Ph1-positive leukemia cell lines. On the other hand, genistein, which was developed as an inhibitor of receptor-type tyrosine kinase, and other protein kinase inhibitors showed no selective inhibition of Ph1-positive leukemia cell growth. Herbimycin A also displayed an abrogative effect on the transformation of murine hematopoietic cells by transfection with a bcr/abl oncoprotein-expressing retroviral vector. The antitumor action of herbimycin A on Ph1-positive leukemia cells is related to an inhibition of activity of bcr/abl protein tyrosine kinase and a subsequent reduction of the constitutive phosphotyrosyl proteins, however, the antibiotic has no effect on the expression of bcr/abl mRNA and oncoprotein. Therefore, herbimycin A may provide an important insight into the oncogenic action of bcr/abl oncoprotein and the future development of oncoprotein-targeted therapeutic agents.

Antibiotics, Antineoplastic↗

PubMed1994

[Studies on respiratory infections in primary care clinic (V). The pattern of distribution on bacteria, Mycoplasma pneumoniae and virus isolated from patients with respiratory infections, who were seen in six private clinics, and clinical efficacy of ciprofloxacin and roxithromycin].

The pattern of distribution of bacteria, Mycoplasma pneumoniae and virus isolated from the same specimen recovered from the throat swab or the sputum of 479 patients with respiratory infections who were seen in six private clinics in Sendai City of Japan during the period from October to November in 1992 (period I) and from January to February in 1993 (period II) was documented. Of the 479 patients, 234 had acute pharyngitis, 145 had acute bronchitis, 96 had influenza, 21 had acute tonsillitis, 5 had acute pneumonia and 9 had other respiratory infections. One hundred (42.4%) strains of potential pathogen and one strain of M. pneumoniae were recovered from 236 cases in period I, and 66 (27.2%) strains of potential pathogen, one strain of M. pneumonae and 73 strains of Influenza virus (30.0%: 43 of type A Hong-Kong and 30 of type B) from 243 cases in period II. Of the 166 strains, major isolates were Staphylococcus aureus (56 strains), Streptococcus pneumoniae (12 strains), Streptococcus pyogenes (15 strains), Haemophilus influenzae (17 strains), Esherichia coli (4 strains), Klebsiella spp. (35 strains), Pseudomonas aeruginosa (4 strains) and Acinetobacter spp. (23 strains). Only one strain of S. aureus was resistant to methicillin (MIC: 50 micrograms/ml). None of S. pneumoniae was resistant to 1 microgram/ml of ampicillin. Ciprofloxacin was administered to 113 cases and roxythromycin to 220 cases by doctors in charge.(ABSTRACT TRUNCATED AT 250 WORDS)

Ciprofloxacin↗

PubMed1994

Effects of acute salt loading on vasopressin mRNA level in the rat brain.

To assess the mutual relationship between acute osmotic stimulation and arginine vasopressin (AVP) gene expression, 2 ml/100 g body weight of 0.9 M NaCl was intraperitoneally administered into conscious rats. They were decapitated to collect blood and brain samples before and 15 min and 1, 3, 6, and 9 h after the injection. The total RNA from the hypothalamus or whole brain tissue was used to determine AVP mRNA by Northern blot analyses with a complementary DNA probe. Plasma AVP and osmolality increased rapidly and transiently 15 min and 1 and 3 h after the injection. AVP mRNA was detected in the hypothalamus but not in the brain tissue without hypothalamus under basal and stimulated conditions. Brain AVP mRNA increased 2.2-fold at 3 h and 1.7-fold at 6 h (P < 0.05-0.01). These increases appeared to be due to the appearance of AVP mRNA with the shorter migration in the gel. These results suggest that an acute osmotic challenge increases AVP mRNA with size heterogeneity within the hypothalamo-hypophyseal tract.

Actins↗

PubMed1994

Effects of an acute water load on plasma ANP and AVP, and renal water handling in hypothyroidism: comparison of before and after L-thyroxine treatment.

To assess whether atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) participate in impaired water excretion in patients with hypothyroid states (HS), an oral acute water loading (WL) test (20 ml/kg.BW/45 min) was performed before and after L-thyroxine (T4) treatment in 5 hypothyroid patients. Plasma ANP, AVP, osmolality (Posm), total protein and renal water excretion were simultaneously determined, and these data were compared to the data from five normal subjects (NS). The impaired water excretion rate in HS was entirely improved in the euthyroid states (ES) after T4 therapy for at least 7 months. Plasma ANP in HS was lower than that in NS (5.9 +/- 0.9 vs. 16.5 +/- 3.6 pmol/L, P < 0.05), but increased after T4 treatment (21.2 +/- 5.7 pmol/L, P < 0.05). Plasma AVP in HS (1.6 +/- 0.5 pmol/L) showed a tendency to be lower than those in ES and NS (2.9 +/- 0.4 and 2.9 +/- 0.7 pmol/L), but did not respond to a fall in Posm after WL, unlike ES and NS. Significant positive correlations were noticed between Posm and plasma AVP in ES and NS, but not in HS. These results suggest that not only the impaired release and/or metabolisms of AVP and ANP, but also derangement of renal water and electrolytes handling might induce attenuation of CH2O formation in hypothyroid states.

Adult↗

PubMed1994

Effects of interleukin-1 beta on blood pressure, thermoregulation, and the release of vasopressin, ACTH and atrial natriuretic hormone.

To assess how interleukins (IL) affect the release of vasopressin (AVP), atrial natriuretic hormone (ANH), and ACTH and the regulation of blood pressure (BP), heart rate (HR) and rectal temperature (RT), the 3 doses of 1.73 (low dose, LD), 8.63 (medium dose, MD), and 43.16 pmol/100 gBW (high dose, HD) of human recombinant IL-1 beta were intravenously (iv) administered in conscious rats, and plasma AVP, ANH, and ACTH, BP, HR and RT were determined simultaneously. In the control group (CON), the drug was omitted. Circulatory IL-1 beta levels were determined in each dose, and indomethacin (1 mg/rat, IM) was administered iv in the HD and CON groups. Plasma IL-1 beta increased transiently following IL-1 beta administration in each group. Plasma AVP, ANH, and ACTH increased in the LD, MD, and HD groups, respectively. Mean arterial BP (MABP) and RT increased in the LD group, but HR did not change. In the MD and HD groups, MABP decreased at 30 min followed by its increase at 120 min, but RT in both groups decreased. In the CON group, these parameters did not change. IM attenuated plasma AVP and ACTH responses to HD and also inhibited decreases in MABP and RT. These results suggest that IL-1 beta affects the release of AVP and ACTH, blood pressure and thermogenesis via prostaglandins (PGs), but ANH release related to IL-1 beta may not be mediated by PGs.

Adrenocorticotropic Hormone↗

PubMed1994

Effects of a nitric oxide synthase inhibitor on vasopressin and atrial natriuretic hormone release, thermogenesis and cardiovascular functions in response to interleukin-1 beta in rats.

To assess whether nitric oxide (NO) formed by IL-1 beta affects vasopressin (AVP) and atrial natriuretic hormone (ANH) release and the regulation of blood pressure and body temperature, intravenous infusion of either N omega-nitro-L-arginine methyl ester (L-NAME) alone (50 micrograms/kg.body weight.min for 135 min), human recombinant interleukin 1 beta (IL-1 beta) alone (750 ng/kg.body weight.min for 120 min), or L-NAME (50 micrograms/kg.body weight.min for 135 min) with IL-1 beta (750 ng/kg.body weight.min for 120 min), was performed following priming doses of L-NAME (2 mg/kg.body weight) and IL-1 beta (7.5 micrograms/kg.body weight) into conscious rats (n = 6 each). In the control group, saline alone was administered. Plasma AVP and ANH, mean arterial blood pressure (MABP), heart rate (HR) and rectal temperature (RT) were determined. In response to L-NAME, plasma AVP significantly increased, but plasma ANH did not change, despite increases in MABP and decreases in HR. In response to IL-1 beta, both plasma AVP and ANH increased with decreases in MABP and RT without any changes in HR. With L-NAME and IL-1 beta, both plasma AVP and ANH increased, and depressor response to IL-1 beta was partly attenuated by L-NAME, without any changes in RT. With saline alone, none of these parameters changed during the study. These results suggest that NO may directly affect the release of AVP and ANH and the regulation of body temperature and blood pressure, but NO formed by IL-1 beta may not have direct effects on the release of these hormones, and the regulation of blood pressure and temperature.

Amino Acid Oxidoreductases↗

PubMed1994

Establishment and characterization of a new Ph1-positive ALL cell line (ALL/MIK) presenting bcr gene rearrangement on bcr-2 and ALL-type bcr/abl transcript: suggestion of in vitro differentiation to monocytoid lineage.

A new Ph1-positive acute lymphoblastic leukemia cell line, designated as ALL/MIK, has been developed from a patient with Ph1-positive acute leukemia. The ALL/MIK cells showed an immunophenotype of common ALL with rearranged JH and Jk genes. The ALL/MIK cells showed no M-bcr rearrangement using Southern blot analysis with either 3' or 5' M-bcr probes, but had the bcr gene rearrangement on bcr-2 within the first intron of the bcr gene. Consistent with this result, the reverse transcriptase-dependent polymerase chain reaction (RT-PCR) assay revealed that the ALL/MIK cells contained the transcript derived fusion of the first exon of bcr gene and the second exon of abl gene. Although the ALL/MIK cells were defined as early pre-B cells by immunophenotypical and genotypical analyses, they were capable of differentiating into monocytoid lineage by when cultured with TPA. Furthermore, another Ph1-positive ALL cell line, (TOM-1), was investigated for its ability to differentiate to monocytoid lineage. TOM-1 was also induced to monocytoid lineage by TPA. Thus, the present study suggested that the leukemic transformation in some Ph1-positive ALL may occur at the level of multipotential hematopoietic cells capable of differentiating towards lymphoid and myelo-monocytoid lineage.

Aged↗

PubMed1994

Specific reactivity of human monoclonal antibody AE6F4 against cancer cells in tissues and sputa from lung cancer patients.

In vitro immunization of normal human peripheral lymphocytes by the co-cultivation with A549 cells (a human lung adenocarcinoma cell line), followed by the hybridization with the partner cell line A4H12, resulted in the efficient generation of hybridomas which produce human monoclonal antibodies of IgG or IgM isotype. Immunohistochemical and immunocytological studies showed that one of those monoclonal antibodies, termed AE6F4, was specifically reactive to lung cancer tissues as well as cancer cells in sputa.

Antibodies, Monoclonal↗