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J Nishimura

Publications and source records attributed to J Nishimura.

At least 163 records · Page 9Linked to original sources
PubMed1995

Cytosolic calcium concentration-force relation during contractions in the rabbit femoral artery: time-dependency and stimulus specificity.

1. By use of front-surface fluorometry with fura-2-loaded rabbit femoral arterial strips, both the cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored. By utilizing the [Ca2+]i-force curves, we were thus able to examine the temporal changes in the relationships between [Ca2+]i and force ([Ca2+]i-force relationship) during contractions induced by a high external K+ solution, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). 2. The 'basic' [Ca2+]i-force relationship of the Ca(2+)-induced contractions was obtained by the cumulative applications of extracellular Ca2+ (0-10 mM) during 118 mM K(+)-depolarization (Ca(2+)-contractions). 3. When each vascular strip was exposed to high external K+ (30 mM K(+)-118 mM K+) solutions, the [Ca2+]i abruptly increased until it reached a peak, and then slightly decreased and eventually reached a steady-state level. The force also rapidly rose to reach a maximum plateau level. The changes in [Ca2+]i were more rapid than those in the force. Thus, the [Ca2+]i-force curves observed during the contractions induced by high+ (30 mM-118 mM) solutions showed a counter-clockwise rotation, over time. The entire curve shifted to the right, in a concentration-dependent manner, as compared with the line of the 'basic' [Ca2+]i-force relationship of the Ca(2+)-contraction. However, the [Ca2+]i-force relationship of the steady-state of contractions induced by the single dose applications of high K+ (30 mM-118 mM) overlapped with the line of the 'basic' [Ca2+]i-force relationship of Ca(2+)-contractions. 4. As references, the levels of [Ca2+]i and the force at rest (without stimulation) and at the steady-state of the contractions induced by a single dose application of 118 mM K+ solution were designated as 0% and 100%, respectively. When the vascular strips were exposed to NA (10(-5) M) and to 5-HT (10(-4) M), the [Ca2+]i abruptly rose, and reached a peak (107.1 +/- 5.8%) and 101.3 +/- 2.8%, respectively) after 1 min and 2 min, respectively (the [Ca2+]i-rising phase), and thereafter declined with a similar time course (the [Ca2+]i-declining phase) until reaching a low steady level (the steady-state phase). The force induced by 10(-5) M NA and 10(-4) M 5-HT reached a peak at 4 min (129%) and at 2 min (115%), respectively, and thereafter gradually declined. In contrast to the similarity in the [Ca2+]i transient between NA and 5-HT, the force induced by NA declined more slowly and reached higher steady levels than that seen with 5-HT. The level of force 20 min after the application of NA and 5-HT was 112% and 72%, respectively.5. In the entire time course of the 5-HT-induced contraction, i.e., in [Ca2+]i-rising, [Ca2+]i-declining and the steady-state phases, the [Ca2+]i-force relation was almost the same as that of the Ca2+-contractions.In the [Ca2+]i-rising phase of NA-induced contraction, the [Ca2+]i-force relation was similar to that of the Ca2+-contractions. However, in the [Ca2+] -declining and the steady-state phases, NA produced a greater force than that expected from a given change in the [Ca2+]i of the Ca2+-contractions, which resulted in a leftward shift of the [Ca2+]i-force relation. The extent of the leftward shift depended on the concentration of NA.6. These results suggest that (1) changes in [Ca2+]i precede changes in the force during the high K+-induced contraction, (2) in the initial [Ca2+]i-rising phase of the contractions induced by NA or by 5-HT, the [Ca2+]i-force relation is similar to that of Ca2+-contractions, and (3) in the subsequent[Ca2+]i-declining and the steady-state phases of the contractions, 5-HT demonstrated little enhancement in force for the given levels of [Ca2+]i, while NA induced a greater force for the given levels of [Ca2+],, in the rabbit femoral artery. Based on the above findings we suggest the presence of a time-dependent and stimulus-specific modulation of the Ca2+ sensitivity in the contractile apparatus of arterial smooth muscles.

Animals↗
PubMed1995

Endothelin-1 and endothelin-3 regulate differently vasoconstrictor responses of smooth muscle of the porcine coronary artery.

1. Using front-surface fluorometry of fura-2 and medial strips of the porcine coronary artery, we investigated mechanisms by which endothelin-1 (ET-1) and ET-3 function as vasoconstrictors. 2. In the presence of extracellular Ca2+(1.25 mM), ET-1 (10(-10)-10(-7) M) increased cytosolic Ca2+ concentrations ([Ca2+]i) and tension, in a concentration-dependent manner. ET-1, at concentrations greater than 10(-8) M, induced an abrupt elevation of [Ca2+]i which reached a transient peak (the first component, [Ca2+]i-rising phase) and subsequently declined ([Ca2+]i-declining phase) to reach a lower sustained phase (the second component, steady-state phase), while the tension rose monotonically to reach a peak and then slightly and gradually declined. ET-1, at concentrations lower than 10(-8) M, induced slowly developing and sustained increases in [Ca2+]i and tension ([Ca2+]i-rising phase followed by steady-state phase). All concentrations of ET-1 increased tension more slowly than [Ca2+]i. 3. In the presence of extracellular Ca2+, ET-3 (10(-8)-10(-5) M) induced concentration-dependent increases in [Ca2+]i and tension. However, the maximal elevations of [Ca2+]i and tension induced by ET-3 were substantially smaller than those induced by ET-1, indicating the involvement of an ETA receptor subtype. ET-3, at concentrations greater than 6 x 10(-7) M, caused biphasic slowly developing increases in [Ca2+]i and tension. At concentrations lower than 10(-6) M, ET-3 caused monophasic increases in [Ca2+]i and tension. At all concentrations of ET-3, the time courses of increases in [Ca2+]i and tension were similar. 4. The biphasic increases in [Ca2+]i and tension induced by 10-5 M ET-3 and by 1O-7M ET-1 were significantly inhibited by pretreatment with 10-5 M of the Ca2+ entry blocker, diltiazem, although the inhibition of the first component of ET-l-induced [Ca2+]i increase was partial.5. In the absence of extracellular Ca2+, ET-1 induced a concentration-dependent transient increase in[Ca2+]i, possibly due to release of Ca2+ from intracellular stores, and a sustained contraction. In contrast, ET-3 ( 10-6 M) caused little, if any, transient increase in [Ca2+]i and a small sustained contraction.6. Temporal changes in the relationships between [Ca2+]i and tension ([Ca2+]1-tension relationship)during contractions induced by ET-1 and ET-3 were compared with the [Ca2+]i-tension relationship of Ca2+-induced contractions (Ca2+-contractions) obtained by cumulative applications of extracellular Ca2+(0-7.5 mM) to tissues depolarized in the presence of 118 mMK+. In the [Ca2+]i-rising phase, ET-1 increased tension more slowly than [Ca2+]i, thereby shifting the [Ca2+]i-tension relation to the right from that for Ca2+-contractions. In the [Ca2+I-declining and the steady-state phases, ET-1, at concentrations higher than 10-9 M, produced greater tension development than that expected from a given change in[Ca2+ji, resulting in a leftward shift of the [Ca2+]i-tension relation. During ET-3-induced contractions,([Ca2+]i-rising, [Ca2+]i-declining and steady-state phases), the [Ca2+]i-tension relation was similar to that of Ca2+-contractions.7. BQ-123, a selective ETA receptor antagonist, completely inhibited the increases in [Ca2+1]i and tension induced by ET-1 and ET-3.8. These results suggest: (1) That ET-1 elicits vasoconstriction by increasing [Ca2+]i through the activation of Ca2+ influx from the extracellular space and Ca2+ release from intracellular storage sites,and by increasing the Ca2+ sensitivity of the contractile apparatus, whereas ET-3 induces vasoconstriction by increasing [Ca2+1] mainly through Ca2+ influx from the extracellular space. (2) Distinct mechanisms of time-dependent modulation of the Ca2+ sensitivity function in the vasoconstrictor responses to ET-1 and ET-3. (3) That both ET-1- and ET-3-induced contractions seem to be mediated via ETA-receptors in porcine coronary artery, and that the ETA-receptor-mediated effects of ET-1 and ET-3 can be dissociated at the sub-receptor levels of the signal transduction pathway.

Animals↗
PubMed1995

Mechanism of endothelium-dependent relaxation induced by substance P in the coronary artery of the pig.

1. Using front-surface fluorometry of fura-2-loaded porcine coronary arterial strips with the endothelium intact, we investigated the mechanisms of vasorelaxation induced by substance P (SP). Fura-2 fluorescence signals which indicated the cytosolic Ca2+-concentration ([Ca2+]i), were observed to arise exclusively from teh smooth muscle cells in these strips. 2. During the contractions induced by U46619 (100 nM), a thromboxane A2 analogue, an SP-induced endothelium-dependent, biphasic vasorelaxation was observed, which consisted of an initial rapid relaxation phase followed by a sustained phase, with a transient decrease in [Ca2+]i. Pretreatment with indomethacin (Ind) had no effect on the SP-induced relaxation; however, pretreatment with NG-nitro-L-arginine (L-NOARG) partially, but significantly inhibited the decrease in both the [Ca2+]i and tension abolished. Thus, part of the relaxation was considered to be mediated by L-NOARG-sensitive relaxing factor (endothelium-derived relaxing factor: EDRF). 3. During the 40 mM K+-depolarization-induced contraction which may eliminate the effects of endothelium-derived hyperpolarizing factor (EDRF), the vasorelaxation reduced by SP was completely inhibited by L-NOARG. 4. During the vasorelaxation induced SP, the [Ca2+]i-tension relationships shifted to the right of the contractions induced by either U46619 or high K+-depolarization. 5. Using front-surface fluorometry of fura-2 loaded porcine aortic valvular strips, we examined the effects of SP on [Ca2+]i in endothelial cells in situ. SP induced a rapid increase in [Ca2+]i of endothelial cells in situ followed by a small sustained phase in normal PSS (5.9 mM K+). The increase in extracellular K+ had no apparent effect on the SP-induced [Ca2+]i elevation of endothelial cells.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Evidence for the presence of endothelin ETA receptors in endothelial cells in situ on the aortic side of porcine aortic valve.

1. In the present study, we determined whether ETA receptors are present on endothelial cells in situ, by use of front-surface fluorometry of fura-2-loaded porcine aortic valvular strips and reverse transcription polymerase chain reaction (RT-PCR). 2. Although endothelin-1 (ET-1) and endothelin-3 (ET-3) induced maximum elevations of cytosolic Ca2+ concentrations ([Ca2+]i) at 10(-7) M, the peak elevations of [Ca2+]i induced by ET-1 were much greater than those induced by ET-3. 3. The application of ET-1 after ET-3 induced an additional increase in [Ca2+]i, while the application of ET-3 after ET-1 had no effect. A selective ETA receptor antagonist, BQ-123, partially inhibited the ET-1-induced Ca2+ transient but had no effect on ET-3-induced Ca2+ transients. These experiments indicated the presence of functioning ETA receptors in addition to ETB receptors in endothelial cells in situ. 4. The sequence of pig lung ETA receptor complimentary DNA (cDNA) was determined by PCR. RT-PCR, using specific primers for pig ETA receptor sequence and total RNA from endothelial cells on the aortic side of the aortic valve, gave the expected size of band. This PCR product was sequenced and was found to be identical to the sequence of the pig lung ETA receptor. 5. The partial sequence of the pig lung ETB receptor was also determined. RT-PCR for the pig ETB receptor revealed that endothelial cells of the aortic valve express ETB receptor messenger RNA (mRNA). 6. We confirmed that functioning ETA receptors and expression of ETA receptor mRNA exist in the endothelial cells on the aortic side of porcine aortic valves.

Amino Acid Sequence↗
PubMed1995

Resting load regulates vascular sensitivity by a cytosolic Ca(2+)-insensitive mechanism.

The cellular mechanism underlying the regulation of the contraction of vascular smooth muscles by resting load is unknown. To determine the effects of changes in the resting load on vascular sensitivity to high K+ and to 9,11-dideoxy-11 alpha, 9 alpha-epoxy-methanoprostaglandin F2 alpha (U-46619), the force and cytosolic calcium concentration ([Ca2+]i) of arterial strips were recorded at resting loads of 200 (optimal load), 50, and 10 mg. A decrease in the resting load elicited a small decrease in the basal [Ca2+]i level without affecting the extent of maximal [Ca2+]i elevation induced by either stimulus. Through a decrease in the resting load, the concentration-response curves for the force development of high K+ or of U-46619 shifted to the right, whereas those for [Ca2+]i did not. We conclude that the basal [Ca2+]i level and the force development, but not the agonist-induced [Ca2+]i signals, of vascular smooth muscles depend on the resting load. We response that the resting load regulates the sensitivity of vascular smooth muscles, irrespective of types of stimuli, through a [Ca2+]i-insensitive mechanism.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Decay-accelerating-factor-deficient erythrocytes during the long-term clinical course of patients with paroxysmal nocturnal hemoglobinuria.

We performed long-term follow-up studies of 5 patients with paroxysmal nocturnal hemoglobinuria (PNH). The percentages of decay-accelerating-factor (DAF)-deficient erythrocytes were almost stable or slowly increased during the 2-4 years' observation periods when the effects of treatment with drugs or blood transfusion and pregnancy were excluded. However, a tendency of increase in the percentages of DAF-deficient erythrocytes was observed along with the duration of the disease. Our findings suggest that the growth advantage of PNH clones beyond the normal hematopoiesis may be different from the other clonal stem cell disorders.

Adult↗
PubMed1995

Which progenitor is the target cell in the development of acute promyelocytic leukemia?

Acute promyelocytic leukemia (APL) is characterized by the t(15;17) which involves the PML gene and the retinoic acid receptor alpha (RAR alpha) gene, and the subsequent PML/RAR alpha fusion gene is a key event in the leukemogenesis of APL. We found that the PML/RAR alpha fusion gene was expressed in both granulocytic/macrophage and erythroid colonies in a few patients with APL. In some instances of acute myelogenous leukemia (AML), erythrocytes or platelets also expressed the glucose-6-phosphate dehydrogenase (G-6-PD) isoenzymes which were detected in the leukemic cells. Some APL cells show basophilic and monocytoid differentiation and these findings suggest that the leukemic precursor of APL is derived from a more primitive cell stage than the promyelocyte. The precursor cells appear to be derived from heterogeneous levels.

Cell Transformation, Neoplastic↗
PubMed1995

Detection of minimal residual disease by reverse transcriptase polymerase chain reaction for the PML/RAR alpha fusion mRNA: a study in patients with acute promyelocytic leukemia following peripheral stem cell transplantation.

Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML) that is characterized by the presence of a PML/RAR alpha fusion gene resulting from t(15;17). Peripheral stem cell transplantation (PSCT) has been used to treat patients with AML. To assess the presence of minimal residual disease (MRD) and the contamination of leukemic cells in peripheral stem cells (PSCs), we examined six patients with APL who were undergoing PSCT, using reverse transcriptase polymerase chain reaction analysis to detect the mRNA of the PML/RAR alpha fusion gene. The fusion gene was expressed in the bone marrow cells during the early phase of a complete remission and in some of the PSCs. Detection of the fusion gene can be useful in monitoring for leukemic cell contamination of PSCs and for predicting a relapse of APL.

Base Sequence↗
PubMed1995

Specific IgE to Japanese cypress (Chamaecyparis obtusa) in patients with nasal allergy.

BACKGROUND: Japanese cedar (Cryptomeria japonica) is the most important pollen causing pollinois during spring. During recent years some patients' nasal symptoms have been getting worse after the Japanese cedar pollen season. Japanese cypress (Chamaecyparis obtusa) pollen is also observed in this period. The purpose of the study was to investigate the effect of Japanese cypress pollen and cross-allergenicity between Japanese cypress and Japanese cedar in patients with allergic rhinitis. METHODS: A total of 267 patients were enrolled in the study. IgE antibodies to both tree pollens were measured by the CAP RAST method. The results of the CAP RAST test were compared with those of skin tests. In order to compare cross-allergenicity between these two pollens, CAP RAST inhibition assay was carried out. RESULTS: The positive frequencies of Japanese cypress and Japanese cedar in 267 patients were 50.1% and 74.7%, respectively. A significant correlation (r = .765) was observed between the two tree pollens. There was good concordance (75%) between RAST and skin tests to Japanese cypress. The results of RAST inhibition assay indicated cross-allergenicity between these two pollens and species-specific allergens. CONCLUSION: Measurement of IgE antibody to Japanese cypress is useful for the diagnosis of pollinois during the spring.

Adolescent↗
PubMed1994

Motilin induces the endothelium-dependent relaxation of smooth muscle and the elevation of cytosolic calcium in endothelial cells in situ.

Using front-surface fluorometry with fura-2 and porcine aortic valvular strips, we investigated the effect of motilin, a gastrointestinal peptide, on the cytosolic Ca2+ concentration ([Ca2+]i) of endothelial cells in situ. Motilin induced a biphasic elevation of [Ca2+]i of the endothelial cells on the porcine aortic valvular strips. To investigate the physiological role of these Ca2+ transients in the endothelial cells, we determined the effect of motilin on [Ca2+]i as well as the tension of the smooth muscles in the porcine coronary strips with an intact endothelium. Motilin decreased [Ca2+]i and the tension of the coronary smooth muscle precontracted by U46619, a thromboxane A2 analogue, in an endothelium-dependent manner. In the presence of indomethacin (a cyclooxygenase inhibitor), motilin induced an endothelium-dependent relaxation of the coronary strips which was partially inhibited by N omega-nitro-L-arginine (L-NNA; a NO synthase inhibitor). These results thus indicate that motilin induces Ca2+ transients of the endothelial cells while it also induces vasorelaxation, which may be mediated by both L-NNA sensitive and resistant factors that are derived from the endothelium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Characterization of genomic PIG-A gene: a gene for glycosylphosphatidylinositol-anchor biosynthesis and paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia characterized by the presence of abnormal subpopulations of blood cells that are deficient in surface expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Recent studies showed that the gene termed PIG-A, which participates in the first step of GPI-anchor biosynthesis, is mutated in the abnormal blood cells from patients with PNH. In this study the genomic PIG-A gene was cloned and characterized to obtain nucleotide sequence information for analyzing somatic mutations of PIG-A in patients with PNH. The PIG-A gene is at least 17 kb long and has six exons. The exon-intron boundaries and 583 bp of the 5' flanking region were sequenced. The 5' flanking region has no TATA-like sequence, but includes four CAAT boxes, two AP-2 sequences, and a CRE sequence, some of which are present in regions necessary for the promoter activity. We report pairs of oligonucleotide primers for polymerase chain reaction that should be useful to amplify and analyze various regions of the PIG-A gene in patients with PNH.

Base Sequence↗
PubMed1994

Protein kinase C and protein kinase A regulate the expression of angiotensin II receptor mRNA in smooth muscle cells.

Using reverse transcription polymerase chain reaction and fura-2 microfluorometry of intracellular Ca2+ concentrations, we investigated the effects of angiotensin II and cyclic AMP on the expression of angiotensin II type 1 receptor mRNA and the relationship between angiotensin II receptor mRNA level and physiological responsiveness in rat aortic smooth muscle cells in primary culture. Angiotensin II (1 microM) induced a time- and dose-dependent transient decrease in the level of angiotensin II receptor mRNA. The maximal decrease (50 +/- 13% of control) occurred at 6 h, followed by a gradual return to the control level within 24 h. H-7 (30 microM), a relatively specific protein kinase C inhibitor, inhibited decrease in the expression of angiotensin II receptor mRNA induced by 6 h angiotensin II treatment, while 6 h stimulation by 0.3 microM phorbol 12-myristate 13-acetate also induced a decrease (35 +/- 8% of control) in the expression of angiotensin II receptor mRNA. An increase in cellular cyclic AMP induced by 10 microM forskolin plus 10 microM 3-isobutyl-1-methyl-xanthine, decreased the angiotensin II receptor mRNA level to 50 +/- 13% of the control at 6 h and increased it to 219 +/- 39% of the control at 48 h of treatment. Angiotensin II-induced decrease and cyclic AMP-induced increase in the expression of angiotensin II receptor mRNA were accompanied by a reduction and enhancement in [Ca2+]i transients induced by angiotensin II, respectively. In contrast with angiotensin II receptor mRNA level (102 +/- 8% of control), the [Ca2+]i transients were markedly decreased in angiotensin II plus H-7 treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1994

Cytosolic Ca2+ transients are not required for platelet-derived growth factor to induce cell cycle progression of vascular smooth muscle cells in primary culture. Actions of tyrosine kinase.

We investigated interrelations among changes in cytosolic Ca2+ concentrations ([Ca2+]i), tyrosine phosphorylation, and the cell cycles of rat aorta smooth muscle cells in primary culture, as stimulated with platelet-derived growth factor (PDGF). Changes in [Ca2+]i were monitored using the microfluorometry of Fura-2. The phase of the cell cycle and the extent of tyrosine phosphorylation were examined by immunocytochemical analysis of monoclonal antibodies against cell cycle-specific nuclear antigens and against phosphotyrosine, respectively. Prior to the application of PDGF, the cell cycle was synchronized in the G0 phase by serum deprivation for 24 h. In the presence of extracellular Ca2+, PDGF induced an initial transient (first component) and a subsequent lower steady-state (second component) elevation of [Ca2+]i. NiCl2 and the removal of extracellular Ca2+ inhibited the second, but not the first, component. The first component was inhibited by pretreatment with ryanodine. These results are compatible with the notion that the first and second components may be mediated mainly through the release of intracellular Ca2+ and the influx of extracellular Ca2+, respectively. After pretreatment with ryanodine and in the presence of NiCl2, PDGF also stimulated the entry of G0 cells into G1 phase, but there were no [Ca2+]i transients. Genistein, a tyrosine kinase blocker, inhibited tyrosine phosphorylation induced by PDGF and blocked the first, but not the second, component of [Ca2+]i elevation induced by PDGF. However, genistein did not inhibit the release of intracellular Ca2+ induced by angiotensin II or by caffeine. Genistein prevented G0 cells from entering the G1 phase, as induced by PDGF, but this was not the case when serum was reapplied to the growth medium. Similar results were obtained with another tyrosine kinase blocker, tyrphostin. These data suggest that in vascular smooth muscle cells: 1) an increase in [Ca2+]i is not required for competent (G0 to G1) cell proliferation induced by PDGF; and 2) tyrosine kinase plays an important role in the release of intracellular Ca2+ and in cell proliferation, as induced by PDGF.

Angiotensin II↗
PubMed1994

Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder in which there is a deficiency in the synthesis by hematopoietic cells of the glycosyl-phosphatidylinositol molecules that anchor proteins to the cell membrane. Recently, we demonstrated that a gene termed PIG-A (for phosphatidylinositol glycan class A), a component of glycosyl-phosphatidylinositol biosynthesis, was responsible for PNH in two patients. The present study was undertaken to elucidate whether PIG-A is the gene responsible for all cases of PNH and to characterize further the somatically acquired abnormalities of this gene. METHODS: We studied granulocytes from 15 patients with PNH. The cell content of CD55 and CD59 was assessed by fluorescence-activated flow cytometry. PIG-A transcripts were reverse-transcribed, amplified by the polymerase chain reaction, and cloned into plasmids. The structure of the cloned complementary DNA was analyzed by nucleotide sequencing, and its function was assessed on the basis of its ability to restore to normal the abnormal phenotype of a PIG-A-deficient cell line after transfection. RESULTS: Three patients had size abnormalities of PIG-A transcripts with different patterns, and in one patient a very low level of the PIG-A transcript was found. Eleven patients had transcripts of normal size, but the transfection assay revealed that in each patient some of them were nonfunctional. The percentage of nonfunctional PIG-A transcripts was correlated with the percentage of affected granulocytes (P < 0.001). Sequence analysis demonstrated somatic mutations in two of the patients. CONCLUSIONS: PIG-A is the gene responsible for PNH in all patients studied to date.

Base Sequence↗
PubMed1994

Adrenalectomy increases local cerebral blood flow in the rat hippocampus.

The present study examined the effect of glucocorticoid manipulations on local cerebral blood flow in the hippocampus. We measured local cerebral blood flow in the hippocampus at 1-h intervals over a 1-day period in freely moving rats, by means of the H2 clearance method, before and after sham adrenalectomy, adrenalectomy or adrenalectomy with corticosterone replacement. We also measured local cerebral blood flow in the prefrontal cortex before and after adrenalectomy. Four weeks after the adrenalectomy, hippocampal blood flow at each time of day was an average of 47% greater than before the operation, showing diurnal variation as before. After the sham adrenalectomy or adrenalectomy with corticosterone replacement, hippocampal blood flow did not change significantly with respect to either its level or its diurnal variation. Local cerebral blood flow in the prefrontal cortex increased by only 19% after adrenalectomy. The present study demonstrates that adrenalectomy causes a remarkable increase in hippocampal blood flow, probably due to a lack of corticosterone.

Adrenalectomy↗
PubMed1994

Late-appearing Philadelphia chromosome in a patient with acute nonlymphocytic leukaemia derived from myelodysplastic syndrome: detection of P210- and P190-type bcr/abl fusion gene transcripts at the leukaemic stage.

We describe a patient with acute nonlymphocytic leukaemia (ANLL) derived from myelodysplastic syndrome in whom the Philadelphia chromosome (Ph1) first emerged at the late stage of ANLL transformation. Cytogenetically, the Ph1 chromosome was not detected until the late stage of ANLL transformation, 14 months after the transformation following a 3-month history of refractory anaemia with excess of blasts. The cells with and without the Ph1 chromosome had a common abnormal chromosome, t(3;3) (q21;q26). The reverse transcription-polymerase chain reaction analysis showed no bcr/abl message at diagnosis. However, the mRNA encoding P210bcr/abl was detected in the early stage of ANLL transformation. Furthermore, the mRNAs encoding both P210bcr/abl and P190bcr/abl were detected in the late stage of ANLL transformation when the Ph1 chromosome was detected by cytogenetic analysis. These evidences support a multistep pathogenesis of leukaemias, and the products of bcr/abl fusion gene may influence the course of disease.

Adult↗