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Biomedical subjects

Y Abe

Publications and source records attributed to Y Abe.

At least 559 records · Page 31Linked to original sources
PubMed1994

A novel form of mouse cytochrome P450 3A (Cyp3a-16). Its cDNA cloning and expression in fetal liver.

A complementary DNA clone coding for a novel form of cytochrome P450, Cyp3a-16, in mouse fetal livers was isolated and completely sequenced. This clone encoded a polypeptide of 504 deduced amino acids and showed 87.3% and 66.6% amino acid identities with mouse Cyp3a-11 and Cyp3a-13, respectively. Cyp3a-16 transcript was detectable before birth and remarkably diminished five weeks after birth in mice. We conclude that Cyp3a-16 is a fetal- and puberty-specific cytochrome P450 in mice.

Amino Acid Sequence↗
PubMed1994

High sensitivity of the turtle olfactory system to nonvolatile substances: comparison of response properties with those in gustatory systems.

The olfactory responses of the aquatic turtles, Geocylemys reevesii whose nostrils are closed underwater to nonvolatile substances were measured by recording the olfactory bulbar responses. Various salts, acids and bitter substances elicited large responses, while sugars and amino acids did not elicit the responses. The thresholds for the salts were much lower than those of corresponding salts in the rat gustatory system. The responses to the salts were partially suppressed by amiloride. Various acids induced large responses and the magnitudes greatly depended on the anion species. The thresholds for the bitter substances were much lower than those of corresponding substances in the taste systems. Similar to the responses in taste systems, both electrostatic and hydrophobic interactions contribute to the binding of the substances to the receptor membranes. Similar to the taste systems, the response to quinine hydrochloride showed a sharp temperature dependence having a peak around 25 degrees C, while the responses to odorants did not show such peak. The present results suggest that the olfactory system has similar abilities to respond to salts, acids and bitter substances to those in gustatory systems and that the high sensitivity of the olfactory system to chemical stimuli is not only attributable to the second messenger amplification system, but also to the basic property of the receptor membrane independent of the amplification system.

Acids↗
PubMed1994

Endothelin-1 activates mitogen-activated protein kinases through two independent signalling pathways in rat astrocytes.

Northern blot analysis and displacement study revealed that the endothelin (ET) receptor functionally expressed in rat primary cultured astrocytes is the ETB receptor. Mitogen-activated protein kinases (MAP kinases) in the cells were activated by 10 nM ET-1, a dose that maximally stimulated phosphoinositide hydrolysis. This activation was potently inhibited by pretreatment of the cells with phorbol 12-myristate 13-acetate (PMA) which leads to protein kinase C (PKC) down-regulation and was slightly inhibited by pretreatment with pertussis toxin (PTX). Pretreatment of the cells with PMA plus PTX completely inhibited the ET-1-augmented MAP kinase activity. Activation of MAP kinases was also induced by 0.1 nM ET-1, which hardly stimulated phosphoinositide hydrolysis. This activation was fully inhibited by pretreatment with PTX but insensitive to pretreatment with PMA. ET-1-stimulated production of inositol phosphates was not affected by pretreatment with PTX. These results suggest that activation of MAP kinases secondary to stimulation of the ETB receptor with ET-1 in rat primary cultured astrocytes was mediated through two independent signalling pathways. PKC-dependent pathway and PTX-sensitive G protein-mediated pathway.

Animals↗
PubMed1994

Amyloid beta protein-induced irreversible current in rat cortical neurones.

The effect of amyloid beta protein (A beta P) was examined in neurones dissociated from rat cortex using the nystatin perforated patch-clamp technique. A beta P at concentrations > 10 nM induced an irreversible slow inward current associated with an increase in membrane conductance. The time lag until the appearance of the effect of A beta P shortened in a concentration-dependent manner. When extracellular Na+ and Cl-, and intracellular K+ were replaced by equimolar N-methyl glucamine, isothionate- and Cs+, respectively, the membrane conductance and the reversal potential were not affected. Even when an internal solution including 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (20 mM) was used, the effect of A beta P did not alter. It is suggested that A beta P binds to the neuronal membrane and opens non-selective ion channels, resulting in neuronal degeneration.

Amyloid beta-Peptides↗
PubMed1994

Nicotinic and muscarinic acetylcholine responses in the embryo chick ciliary ganglion cells.

Nicotinic and muscarinic acetylcholine (ACh) responses were investigated in acutely dissociated chick ciliary ganglion neurons using the nystatin perforated patch clamp technique. ACh-induced a rapid transient inward current in 100% of the neurons at a holding potential of -60 mV. This rapid inward current was mimicked by nicotine but not by muscarine. The reversal potential of the rapid inward current was +10.5 mV and the current was inhibited by d-tubocurarine and hexamethonium in a dose-dependent manner. In 57.6% of neurons, a slow inward current was also induced by ACh at a holding potential of -20 mV. This slow inward current was mimicked by muscarine but not by nicotine. The slow inward current became smaller at a hyperpolarized potential but not reversed, being consistent with the fact that this current was elicited by the inhibition of M-current. p-Fluorohexa-hydrosiladifenidol (P-F-HHSiD) strongly inhibited the slow inward current, suggesting that the current was elicited by the activation of M3 receptors.

Acetylcholine↗
PubMed1994

Amino acid-induced responses in CNS neurons of normal mouse and Wriggle Mouse Sagami.

Amino acid-induced responses and their regional heterogeneities in the motor cortical and hippocampal (CA1) neurons of normal mouse and Wriggle Mouse Sagami (WMS) were studied by conventional patch-clamp techniques. There were no differences in the current densities and EC50s of glutamate-, gamma-amino butyric acid (GABA)-, and glycine-induced responses between the two groups of mice. In both types of mice, the GABA-induced current density of cortical neurones was higher and EC50 was lower than in hippocampal neurones, whereas the responses induced by glycine and glutamate did not show any differences.

Animals↗
PubMed1994

[Case report of sister with Duane's syndrome and PGA, or myasthenia gravis].

We report a case of polyglandular autoimmune syndrome (PGA) complicated by Duane's syndrome. The patient was 44-year-old female with marked limitation of abduction in the left eye, lethargy, nonhomogeneous facial pigmentation, goiter, and oligomenorrhea. A diagnosis of chronic thyroiditis was first made to explain the patient's symptoms. Laboratory examinations were performed. Plasma ACTH level was high and plasma cortisol was low, and there was no response to the ACTH stimulation test. The presence of primary adrenocortical deficiency was confirmed. Moreover, primary gonadal failure was also present, and the diagnosis of PGA type II was made. The patient's elder sister had myasthenia gravis which is a condition known to occur with PGA type II. Therefore, the sister was also suspected to have PGA type II, as the syndrome can occur in family members. However, since she had been receiving large doses of steroids for her myasthenia gravis, laboratory findings were inconclusive. Duane's syndrome, which is characterized by congenital oculomotor disturbance, was also seen in the sister. It is still unknown whether the familial occurrence of Duane's syndrome has a genetic basis. There have been reports of congenital disorders occurring in combination with autoimmune diseases. Further investigation into the relationship between congenital anomalies and autoimmune diseases is necessary.

Adult↗
PubMed1994

Effect of adding phosphorylation sites for cAMP-dependent protein kinase to rat testis 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

In contrast to liver and heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases, the testis isozyme lacks a phosphorylation site for cAMP-dependent protein kinase. In order to determine the effect of phosphorylation site location for the protein kinase on rat testis bifunctional enzyme, consensus amino acid sequences (RRXS) were added at different distances from the N-terminus by site-directed mutagenesis. The expressed wild-type enzyme (WT) and mutant enzymes containing a phosphorylation site at Ser7 (mutant enzyme RT2KS7, where RT2K = rat testis 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase), Ser15 (RT2KS15), or Ser30 (RT2KS30) were purified to apparent homogeneity. All the mutant enzymes served as substrates for the protein kinase, and the phosphate incorporation was over 90%. The Km values of protein kinase A for RT2KS7, RT2KS15, and RT2KS30 were 250 microM, 110 microM, and 50 microM, respectively, and the relative rates were 1, 8, and 23. Various kinetic parameters of dephospho and phospho forms of these enzymes were determined. The kinetic constants of the dephospho form of RT2KS30 were similar to those of WT, but those of RT2KS15 and RT2KS7 showed an 8-fold increase in KmFru6P, an approximately 30% decrease in the Fru-6-P,2-kinase activity, and a 3-fold increase in fructose-2,6-bisphosphatase activity. Phosphorylation of RT2KS30 resulted in a shift in the Fru-6-P saturation curve from Michaelis-Menten kinetics to sigmoidal, with increased KmFru6P and activation of fructose-2,6-bisphosphatase. The kinetic constants of RT2KS15 and RT2KS7 were not altered by phosphorylation. All the mutant enzymes were more sensitive to heat inactivation than was WT.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Activin A stimulates mitogenesis in Swiss 3T3 fibroblasts without activation of mitogen-activated protein kinases.

Activin A stimulated DNA synthesis and transient c-fos expression in quiescent Swiss 3T3 fibroblasts. The activin A-induced DNA synthesis was dose-dependent with a half-maximal effect obtained at 0.3 nM. The maximal response obtained at 10 nM was comparable with that induced by 5 ng/ml basic fibroblast growth factor. Swiss 3T3 fibroblasts expressed abundant high affinity binding sites for 125I-labeled activin A with a Kd value of 0.63 nM and the number of binding sites at 24,000/cell. Northern blot analysis revealed that Swiss 3T3 fibroblasts express a high level of type II activin receptor mRNA. In an attempt to elucidate the mechanism of mitogenic action of activin A, we examined the effect of activin A on mitogen-activated protein kinase activation. Unexpectedly, however, activin A did not induce kinase activation under conditions in which basic fibroblast growth factor and endothelin-1 at similar or even less potent mitogenic concentrations did. Furthermore, activin A did not induce phosphorylation of the Erk2 species of mitogen-activated protein kinase. These observations strongly suggest that the activation of mitogen-activated protein kinase is not a necessary step for activin A-induced DNA synthesis in Swiss 3T3 fibroblasts.

3T3 Cells↗
PubMed1994

Histochemical demonstration of hydrogen peroxide production by leukocytes in fixed-frozen tissue sections of inflammatory lesions.

The production of H2O2 by cells in cold paraformaldehyde-fixed frozen sections of inflammatory lesions was histochemically demonstrated by incubating them with diaminobenzidine (DAB) for 2 to 6 h. Catalase (150 micrograms/ml, about 1400 U/ml) inhibited the reaction, indicating that H2O2 was required to produce the chromogenic DAB product. Granulocytes (PMNs and eosinophils) were the main types of cells stained by the DAB reaction. Positive staining of macrophages was less frequent. The H2O2 was produced by metabolic enzymes that were still active after cell death and mild fixation. An atmosphere of 95 to 100% oxygen enhanced the specific DAB reaction, and an atmosphere of 100% nitrogen eliminated it. The DAB histochemical reaction to detect H2O2 requires the presence of peroxidases to produce the colored reaction product. Within our tissue sections, such peroxidases were evidently present in excess, because addition of low concentrations of H2O2 significantly increased the reaction product. Although some of the H2O2 produced by the granulocytes may have been derived from the dismutation of superoxide (O2-), the NADPH oxidase pathway for O2- formation did not seem to be involved: NADPH oxidase, a rather labile enzyme, should not be active after mild fixation, and diphenyleneiodonium (100 microM), an inhibitor of flavine-requiring NADPH oxidase, did not inhibit the reaction. Reactive nitrogen intermediates were also not involved, because NG-monomethyl-L-arginine and NG-nitro-L-arginine methyl ester, inhibitors of nitric oxide synthetase, did not appreciably inhibit the reaction. We conclude that stable, non-flavine-requiring oxidases, possibly cyclooxygenases or lipoxygenases, produced the H2O2 measured histochemically by our DAB reaction. These studies were made on tissue sections of acute dermal inflammatory lesions produced in rabbits by the topical application of 1% sulfur mustard [bis(2-chloroethyl) sulfide] in methylene chloride. Both intact PMNs and disintegrating PMNs in the base of the crust produced H2O2. Despite the production of H2O2 and the presence of peroxidase activity, no tissue damage was seen microscopically near the H2O2-producing cells, which indicates that the tissues are well protected by the antioxidants present in this self-limiting inflammatory reaction.

Amitrole↗
PubMed1994

Tumor-derived components were responsible for suppression of ornithine decarboxylase activity in the rat wounded skin.

To elucidate the principal cause of delayed wound healing in a tumor-bearing host, the effect of Yoshida sarcoma-derived components on dermal wound healing was investigated in rats with the aid of ornithine decarboxylase (ODC) activity and in vivo bromodeoxyuridine (BrdU) labeling index. The ODC activity in the wounded skin decreased 3 and 7 days after intraperitoneal inoculation of Yoshida sarcoma cells (378.0 +/- 37.3 on Day 3, 280.0 +/- 140.0 on Day 7 vs. 809.3 +/- 109.5 pmol/mg protein/hour on Day 0). When administered 24 hours before and immediately after wounding, the crude nuclear component of the tumor cells significantly decreased the ODC activity in the wounded skin as compared with the control (185.9 +/- 159.8 vs. 534.0 +/- 59.1), but the non-nuclear component was not effective. When nuclear extracts of Yoshida sarcoma cells were intraperitoneally administered immediately after wounding, the 0.15 M or 0.35 M NaCl extract significantly suppressed ODC activity in the wounded skin (233.5 +/- 14.5 and 352.3 +/- 63.2 pmol/mg protein/hour, respectively) in comparison to the control (445.9 +/- 73.6). The BrdU labeling index of epidermal basal cells adjacent to the edge of the wound decreased up to 52% of the control by injection of the 0.15 M extract. It seems that tumor-derived nuclear components may be responsible for delayed wound healing which is commonly observed in cancer cachexia.

Animals↗
PubMed1994

Defects of immune cells in the senescence-accelerated mouse: a model for learning and memory deficits in the aged.

We investigated immune characteristics of SAMP8 mice that have early learning and memory deficiencies and a short life span accompanied by normal growth and compared them to those of SAMR1 mice that have a normal aging process. The indexes of immune responsiveness used were natural killer (NK) cell activity, in vitro anti-SRBC (sheep red blood cells) antibody responses, cell proliferation, and interleukin 2 (IL-2)-producing activity in response to concanavalin A of spleen cells. As early as 2 months after birth, SAMP8 mice showed markedly low activity for all the indexes that was not due to a delay of their development. Endogenous NK cell activity in SAMP8 mice remained low or at the background level for a few months, but the trace level of this activity increased after treatment with an immune potentiator of polyinosinic-polycytidylic acid. Because the number of cells bearing an NK cell marker in SAMP8 mice was comparable to that for SAMR1 mice, the low NK cell activity found for SAMP8 mice may not be caused by a low number of precursor cells but by defects in the lytic mechanism or low competence. Flow cytometry analyses showed that the size of the lymphocyte fraction in the spleen is the same for both strains and that T cell fractions, especially of CD4+ T cells in SAMP8 mice are smaller than in SAMR1 mice. In contrast, a B cell fraction was somewhat larger in SAMP8 mice. Together with the fact that the spleen cells of both strains equally stimulated allogeneic T cells in the mixed lymphocyte reaction, the low helper T cell activity in antibody responses, even under the condition of cell-number equivalence, indicates a qualitative defect of CD4+ T cells in SAMP8 mice. This defect probably is closely related to the low endogenous activity of NK cells.

Aging↗
PubMed1994

The effect of blood volume replacement on the mortality of head-injured patient.

In 77 head-injured and transfused patients, the amount of blood volume replacement (BVR) and patient outcome were retrospectively analyzed. They were divided into four groups of intracranial lesion by initial CT; acute subdural hematoma (SDH) with or without other lesions, traumatic subarachnoid hemorrhage only, epidural hematoma only and all other lesions. Result shows SDH is the most vulnerable to massive transfusion and BVR more than 5000 ml was fatal. Patients with other lesions have high possibility of survival even if BVR amounts to 7000ml. It is concluded, for patients resuscitated with excessive amount of transfusion (> 5000 ml), follow up CT and some vigorous treatment such as administration of hypertonic solutions should be scheduled.

Adolescent↗
PubMed1994

Ultrastructural localization of P-glycoprotein on capillary endothelial cells in human gliomas.

The P-glycoprotein (P-Gp) encoded by the human multidrug-resistance gene MDR1 has been suggested to play certain roles in the blood-brain barrier (BBB). However, the detailed mechanism of the activity of P-Gp in multidrug-resistance (MDR) remains unclear in human glioma. We examined the localization of P-Gp in human glioma by immunohistochemical (IHC) and immunoelectron microscopic (IEM) methods with anti P-Gp monoclonal antibodies (C219, MRK16). We also examined MDR1 expression in primary glioma and xenografts by reverse transcription-polymerase chain reaction (RT-PCR) with human MDR1-specific primers. The IHC study showed no P-Gp expression on tumour cells but it was present on capillary endothelial cells and IEM analysis showed definitive localization on their luminal surface. MDR1 gene expression was detected in eight primary glioma and three normal brain specimens by RT-PCR, but not in glioma xenografts. The lack of MDR1 expression in these cells appears to be a consequence of the replacement of the original human stroma, including blood vessels, by murine stroma in glioma xenografts. The unique distribution of P-Gp on the capillary blood vessels was confirmed in human glioma by the results of immunohistochemical and molecular biological studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

The elevation of plasma soluble tumor necrosis factor receptor levels by TNF induction therapy for patients with malignancy.

Soluble tumor necrosis factor receptor (sTNF-R) is known to inhibit patient immunity via specific binding with the TNF molecule. To examine the possible involvement of sTNF-R in cancer immunotherapy, the plasma levels of sTNF-R of both 55 kDa and 75 kDa origins were estimated when TNF was induced in patients with malignancy using both a polysaccharide preparation (Lentinan) and a streptococcal preparation (OK-432). The pretreatment plasma levels of the 55 kDa and 75 kDa sTNF-R were 1.04 +/- 0.53 and 1.06 +/- 0.34 ng/ml (mean +/- SE), respectively. The plasma levels of TNF were undetectable before treatment. The plasma sTNF-R levels peaked 2 h after the administration of OK-432 and followed the same pattern as the TNF levels in plasma. Both TNF and sTNF-R nearly returned to pretreatment levels at 16 h after the induction of TNF. The peak plasma levels of the 55 kDa and 75 kDa sTNF-R were 2.46 +/- 0.95 and 3.03 +/- 0.88 ng/ml, respectively, but they did not correlate with the plasma TNF levels. When peripheral white blood cells were cultured with the addition of lipopolysaccharide in vitro, an elevation of the 72 kDa sTNF-R was detected. Thus, the plasma source of this soluble receptor can at least be partly attributed to the white blood cells. However, the 55 kDa sTNF-R showed little increase in the cultures, and its source remains unknown. We should therefore be aware of the elevation of plasma sTNF-R levels by the induction therapy of TNF for patients with malignancies because of the immunosuppressive effect of sTNF-R.

Adult↗