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Biomedical subjects

A Sato

Publications and source records attributed to A Sato.

At least 505 records · Page 28Linked to original sources

Aberrant progenitors common to megakaryocytic and myeloid cells in a Down's infant with transient abnormal myelopoiesis.

Phenotypic characteristics of blasts were studied in a Down's infant with transient abnormal myelopoiesis (TAM). Two major subpopulations were identified: (1) CD33+CD42b+ cells with platelet peroxidase activity, the commitment of which to megakaryocytic lineage was supported by an increased expression of GATA-1 mRNA; (2) CD33+CD34+CD7+CD4+ cells with immature ultrastructure, which could be either immature megakaryocytic or myeloid cells with aberrant differentiation. Mixed colonies containing megakaryocytes and monocyte/macrophages in the peripheral blood suggested the presence of progenitors common to these subpopulations. These results may indicate that subpopulations of blasts with phenotypic diversity could be derived from aberrant common progenitors to megakaryocytic and myeloid lineages in this patient.

Blotting, Northern↗

A novel translocation involving chromosomes 2, 9, 14, and 22 in chronic myeloid leukemia.

A 46-year-old man with chronic myelogenous leukemia was found to have a new complex translocation. In chronic phase, all of the bone marrow cells had a rearrangement of a t(2;9;14;22) (p21;q34;q32;q11). Southern blot analysis of leukocyte DNA revealed rearrangement of the breakpoint cluster region (bcr) within the 5.8-Kb bcr. The patient eventually died in blast crisis 28 months later. The cytogenetic findings of bone marrow cells showed a 46,XY,t(2;9;14;22)(p21;q34;q32;q11),add(1p),del(3q) karyotype in blast crisis.

Chromosome Banding↗

A simple and rapid method for preliminary evaluation of in vivo efficacy of anti-HIV compounds in mice.

In vivo efficacy of anti-HIV compounds is affected by various factors such as bioavailability, metabolism, clearance, and toxicity. Here we report a simple and rapid method that might be useful for preliminary evaluation of in vivo efficacy of anti-HIV compounds. MT-4 cells carrying proviral HTLV-1 were infected with HIV-1 in vitro and injected into the peritoneal cavity of SCID mice or BALB/c mice. Inoculated cells survive for 1-2 days, and support one to two cycles of viral replication which can be monitored by RT activity or p24 content in the supernatants of peritoneal wash fluids. Test compounds were administered either orally or subcutaneously. AZT, DDC and DDI, the nucleoside-type RT inhibitors currently in clinical use, all showed potent anti-HIV-1 activities in this mouse/MT-4 assay. HEPT (E-EBUdM), a non-nucleoside RT inhibitor, also showed potent anti-HIV-1 activity in vivo, whereas TIBO (R82913), another non-nucleoside RT inhibitor, was less active. In protease inhibitors KNI-272 and Ro 31-8959 showed good in vivo activities, while KNI-144, a compound closely related to KNI-272, showed poor in vivo activity. This mouse/MT-4 assay, although having a number of shortcomings as an animal model for HIV-1 infection, may be of some practical utility for preliminary evaluation of in vivo efficacy of potential anti-HIV compounds.

Animals↗

Somatocardiovascular reflexes in anesthetized rats with the central nervous system intact or acutely spinalized at the cervical level.

The effects of noxious mechanical stimulation of various segmental areas on heart rate and mean arterial blood pressure (MAP), as well as cardiac and renal sympathetic nerve activities were examined in anesthetized rats with the central nervous system (CNS) intact or acutely spinalized at the cervical level. In CNS-intact rats, pinching for 20 s applied to any segmental skin area, but particularly that of the paw, produced an increase in heart rate, blood pressure and the sympathetic nerve activities. In acutely spinalized rats, pinching the chest, abdomen and back of the body produced large increases, while hindlimb and perineum stimulation induced only a small increase or no increase in heart rate, blood pressure and the sympathetic nerve activities. Stimulation of the right side produced particularly large responses in heart rate and stimulation of the ipsilateral side produced large responses in cardiac and renal sympathetic nerve activities in spinalized rats. These results suggest the existence of the two types of reflex responses, supraspinal and propriospinal, in the somatocardiovascular reflex. The supraspinal one has characteristics of diffuse reflex organization, while the propriospinal one has strong segmental and lateral organization.

Animals↗

The inhibitory role of nitric oxide (NO) in the somatocardiac sympathetic C-reflex in anesthetized rats.

The role of nitric oxide (NO) in the two somatosympathetic reflex arcs, i.e. A- and C-reflexes, was examined using NO synthase (NOS) inhibitor in anesthetized rats. The A- and C-reflex components were recorded from a cardiac sympathetic efferent nerve and elicited by stimulation of myelinated A and unmyelinated C afferent fibers in the left tibial nerve. NG-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, when administered by either intrathecal (i.t.) or into the cisterna magna (i.c.m.) routes, augmented only the C-reflex in a dose-dependent manner. The effective i.t. dose of L-NAME to augment the C-reflex was approximately 1000 times the i.c.m. dose. NG-nitro-D-arginine methyl ester (D-NAME), an isomer of L-NAME, had no effect on either A- or C-reflexes, when administered i.c.m. Neither i.c.m. pre-treatment nor post-treatment with L-arginine, a NOS substrate, influenced either A- or C-reflexes, but i.c.m. pre-treatment with L-arginine abolished the facilitatory effect of L-NAME on the C-reflex. These results suggest that NO, synthesized in the brain stem, plays an inhibitory role in the central modulation of the somatocardiac sympathetic C-reflex. The possibility of movement of L-NAME to the brain stem from the spinal cord is discussed.

Anesthesia↗

Long-lasting facilitation and depression of periurethral skeletal muscle following acupuncture-like stimulation in anesthetized rats.

The effects of acupuncture-like stimulation on the tone of the partially filled bladder and on the periurethral electromyogram (EMG) were examined in urethane-anesthetized rats. Acupuncture-like stimuli were usually applied to the skin and underlying muscles (or other structures), either separately or together, for a period of 1 min; the effects were studied in spinal cord intact and in spinalized animals. Maps have been constructed showing the effects of acupuncture-like stimulation at different sites on the body surface and of similar stimulation applied to individual muscles, the urethra and the testis. When acupuncture-like stimuli were applied to the skin and underlying structures, in the rostral half of the body and the hindpaw, testis or urethra, these stimuli usually induced excitation of periurethral EMG activity. Depression of EMG activity was seen predominantly during stimulation of structures close to the urethra, but not opposed to it. When acupuncture-like stimuli were applied only to structure beneath the skin, depression of EMG activity usually occurred. Acupuncture-like stimulation of the bulbocavernosus, which partly overlies the proximal urethra produced depression of EMG activity in 50% of trials, but the incidence of similar effects from the more distant pubococcygeus, or the dorsal or ventral sacrococcygeal muscles was about 90-100%. Acupuncture-like stimulation for 1 min could produce either excitation or depression of periurethral EMG activity lasting about 5 or 6 min, depending on the site of insertion and rotation of the acupuncture needles. Excitation of short duration (less than 3 min) was consistently observed from areas of the body distant to the bladder, i.e. the nose, forepaw, forelimb, chest, abdominal wall and hindpaw. Longer lasting excitation of EMG activity was often seen from the penile urethra, perineal area and hindlimb. Depression of EMG activity with a duration of more than 3 min was consistently seen from the muscles at the base of the tail (sacrococcygeus) and perineal area (pubococcygeus and bulbocavernosus). The bladder was partially filled in these experiments, so that micturition contractions were never seen; acupuncture-like stimulation of the perineal area induced some increase in bladder tone in 40% of trials. In spinalized animals, the pattern of activity induced by acupuncture-like stimulation was similar to that seen in spinal cord intact animals and the durations of the effects were not significantly different in these two groups. The distribution of sites from which acupuncture-like stimuli can influence the activity of the lower urinary tract is discussed.

Acupuncture Therapy↗

The influence of afferent inputs from skin and viscera on the activity of the bladder and the skeletal muscle surrounding the urethra in the rat.

(1) Somato-visceral and viscero-visceral reflex interactions have been studied in the bladder branches of the pelvic nerve and in the electromyographic (EMG) activity of the periurethral skeletal muscles of the anesthetized rat, and by observations of changes in bladder motility. (2) Slow distensions of the bladder caused some elevation of intravesical pressure, and culminated in a micturition contraction. Periurethral EMG activity increased gradually during the bladder distension, and showed an oscillatory marked increase during the bladder contraction. There was a small increase in pelvic nerve efferent activity during slow distension, and there was a substantial increase before, or at the start, of a micturition contraction. (3) Oscillatory bursting activity occurred in recordings of the EMG activity from periurethral skeletal muscle during the rising phase of micturition contraction; this was particularly so during the most rapid rise in intravesical pressure, and periods of electrical silence lasting 80-270 ms alternated with bursts of activity in the periurethral EMG. (4) In the present experiments, the switching mechanism activated by pelvic afferent signals related to intravesical pressure reversed the behavior of a number of reflex pathways. When the bladder pressure was low, nociceptive pinching of the perineal skin usually caused bladder contraction and a rise in pelvic nerve efferent activity and in periurethral EMG activity. When the bladder was full, micturition contractions were present and reduced in size and frequency by pinching of the perineal skin. The pelvic nerve efferent activity was correspondingly reduced, while the EMG activity increased during and following the nociceptive stimulus. Cooling the scrotal skin with ice also decreased the frequency of bladder contractions. (5) When the bladder pressure was low, distension of the anus and colon increased periurethral EMG activity, but did not affect bladder tone. However, when the bladder was full, these stimuli reduced the size and frequency of bladder contractions, associated with a reduction in the pelvic nerve efferent activity. There was usually a simultaneous reduction in the EMG activity in periurethral muscles. Similar results were obtained during distension of the seminal vesicles or vagina, or following injection of 20-60 microliters of saline into the lumen of the vas deferens. Reversal of the responses at extremes of intravesical pressure was observed in every case. (6) Following spinal transection at the upper cervical or thoracic level, micturition contractions were absent at high bladder volumes. However the effects described when the neuraxis was intact and the bladder pressure was low were still observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Glucocorticoid-induced hypertension in the elderly. Relation to serum calcium and family history of essential hypertension.

To explore the syndrome of glucocorticoid-induced hypertension in the elderly, we analyzed the clinical findings from 35 patients aged more than 65 years (12 men, 23 women) who received glucocorticoid therapy. Resting blood pressures (BP) were less than 140/90 mm Hg before glucocorticoid therapy, and patients were apparently disease-free apart from the condition for which glucocorticoid therapy was prescribed. Glucocorticoid-induced hypertension is defined as systolic BP more than 160 mm Hg and/or diastolic BP more than 95 mm Hg after glucocorticoid administration. Glucocorticoid-induced hypertension was seen in 13 patients (37.1%); all patients with hypertension [steroid (glucocorticoid)-induced hypertension (SH(+)) group] received more than 20 mg of prednisolone daily, and BP rose rapidly within a week of commencing glucocorticoid administration. The SH(+) group did not differ significantly in terms of age, heart rate, blood count, plasma biochemistry, plasma renin activity, plasma aldosterone, routine urinalysis, or urinary electrolytes from patients who did not show hypertension [SH(-) group]. However, serum total calcium concentrations were significantly lower in the SH(+) group both before and after 2 weeks of glucocorticoid therapy than in the SH(-) group. Furthermore, the SH(+) group showed a significantly higher percentage of patients with a positive family history of essential hypertension than the SH(-) group. In conclusion, although the detailed mechanisms are as yet uncertain, glucocorticoid-induced hypertension occurs often in elderly patients, and is more common in patients with total serum calcium concentrations lower than the normal range, and/or in those with positive family history of essential hypertension.

Aged↗

Intracytoplasmic sperm injection using immobilized or motile human spermatozoon.

OBJECTIVES: To investigate the efficacy of the treatments for oocyte activation on the results of intracytoplasmic sperm injection using immobilized or motile human spermatozoa. DESIGN: The protocol of intracytoplasmic sperm injection was divided into four groups according to the states of sperm used for microinjection and the treatment for oocyte activation. In group A, immobilized sperm is used. The oocyte is activated merely by aspiration of the cytoplasm into the pipette. In group B, immobilized sperm is used. Microinjected oocyte is treated with A23187. In group C, immobilized sperm is used. Electroporation is performed on the microinjected oocyte. In group D, motile sperm is used. The oocyte is activated merely by aspiration of the cytoplasm into the pipette. SETTING: The Obstetrics and Gynecology Hospital, Fukushima Medical College. PATIENTS: The subjects are the cases that had failed fertilization in standard IVF, cases of severe oligozoospermia, and cases of severe asthenozoospermia. RESULTS: No difference was found between the groups as to the survival rate and fertilizing rates of oocytes after intracytoplasmic sperm injection. The cleavage rate of oocytes was high in order of group D, C, B, A. The cleavage rate for groups D, C, and B was significantly higher than group A. Cases of pregnancy were found in groups D and B. CONCLUSION: Using motile sperm rather than immobilized sperm can be expected to produce better results in human ICSI. Activating oocytes positively is needed when immobilized sperm is used.

Cleavage Stage, Ovum↗

Effects of endothelins on mechanical activity and inositol phosphate production in pregnant rat myometrium.

Endothelins (ETs) caused concentration-dependent contraction in pregnant rat myometrium. ET-2 was as potent as ET-1 in affecting contractile responses, whereas ET-3 was considerably less potent than ET-1 or ET-2. ETs also increased inositol phosphate (IP) production in a dose-dependent manner, with IP production paralleling the contractile response. The rank order of potency for both the contractile responses and IP production was ET-1 = ET-2 > ET-3. When we compared the important oxytocic agent oxytocin, we found that oxytocin (10(-7) M) strongly increased contractility and IP production, and the responses were comparable to those elicited by ET-1 (10(-7) M) and ET-2 (10(-7) M). These results suggest that ET-induced myometrial contraction involves phospholipase C activation, and that a subtype of endothelin receptor existing in pregnant rat myometrium could be classified as ETA.

Animals↗

Cholinergic neural regulation of regional cerebral blood flow.

Local metabolites have long been considered to play an important physiological role in regulating regional cerebral blood flow (rCBF). However, the evidence reviewed here emphasizes that the regulation of (rCBF) by central cholinergic nerves is independent of regional metabolism. Activation of the intracranial cholinergic fibers originating in the nucleus basalis of Meynert (NBM) and septal complex releases acetylcholine in the cortex and hippocampus, which results in vasodilation and an increase in rCBF in the cortex and hippocampus. Such intracranial cholinergic vasodilative nerve fibers do not belong to the autonomic nervous system according to the traditional definition by Langley, but interestingly, these fibers behave in the brain similarly to the action of autonomic nerves in peripheral organs. The NBM could be transiently stimulated to increase rCBF by nonpharmacological methods. For example, cutaneous sensory stimulation activates the cholinergic nerves originating from the NBM to enhance rCBF. The increase in rCBF at the diffuse cortices during walking appears to include an excitation of this NBM-originating cholinergic vasodilation system. Other various inputs to the NBM may have a similar effect to enhance rCBF via activation of that cholinergic system, provided the stimulation is delivered properly. Thus the combination of pharmacological and non-pharmacological techniques may provide a balance in our attempts to improve cholinergic replacement therapy.

Acetylcholine↗

Targeting of chrolamphenicol acetyltransferase to human immunodeficiency virus particles via Vpr and Vpx.

Vpr and Vpx are the auxiliary proteins of human immunodeficiency viruses (HIVs) selectively incorporated into mature viral particles. We showed that the bacterial chloramphenicol acetyltransferase (CAT) fused to the N-terminus of HIV-1 Vpr, HIV-2 Vpr, or HIV-2 Vpx was incorporated into mature virions in a type-selective manner. By using chimeric proteins between HIV-1 Vpr and HIV-2 Vpx, we found that the N-terminal side of these proteins was mainly important for type-selective virion incorporation. The C-terminal arginine-rich region of HIV-1 Vpr was also found to transport CAT fusion proteins into virions but without any type selectivity. Furthermore, the corresponding regions of HIV-2 Vpr and HIV-2 Vpx had no such activity. This region of HIV-1 Vpr may interact nonspecifically with viral genomic RNA. Collectively, Vpr and Vpx may provide a means to introduce foreign proteins and other molecules into HIV virions for therapeutic purposes.

Amino Acid Sequence↗

[The bactericidal effects of an amphoteric surfactant with ethanol against Mycobacterium tuberculosis].

Bactericidal activities of an amphoteric surfactant (12 w/v% Alkyl diaminoethylglycine hydrochloride, 3 w/v% Alkyl dietylenetriaminoglycole hydrochloride, Nissan Anon #300, Inui Shouji Co., ADG) against Mycobacterium tuberculosis were examined independently or in cooperation with ethanol. The results obtained in the study are as follows: 1. In the treatment with the surfactant diluted with distilled water in one hundredth, the numbers of tubercle bacilli which survived were 500 cfu/0.1 ml after one minute-treatment, and 25 cfu/0.1 ml after ten minutes-treatment. On the other hand, the surfactant containing 23 v/v% ethanol decreased the bacterial numbers to seven cfu/0.1 ml after one minute and less than one cfu/0.1 ml after ten minutes. The numbers of the survived bacilli treated with the surfactant containing 20 v/v% ethanol were 500 cfu/0.1 ml after one minute-treatment, and less than one cfu/0.1 ml after ten minutes though 20 v/v% ethanol alone was ineffective in ten minutes-treatment. 2. The bactericidal activities of the surfactant against tubercle bacilli in sputum samples in which 1.65 x 10(4) cfu/0.1 ml of the organism were contained were also investigated. The numbers of tubercle bacilli which survived were 25 cfu/0.1 ml after one minute-treatment with the surfactant in one fiftieth, two cfu/0.1 ml after five minutes-treatment and one cfu/0.1 ml after ten minutes-treatment. The numbers of the organism treated with the surfactant containing 23 v/v% ethanol were less than one cfu/0.1 ml after five minutes. 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Resistance, Microbial↗

Enhanced migration of fibroblasts derived from lungs with fibrotic lesions.

BACKGROUND: The migration and proliferation of fibroblasts may be important in the pathogenesis of pulmonary fibrosis. Considerable data are available on the proliferation of fibroblasts, but very few on their migration. METHODS: The migratory activity of fibroblasts obtained from lung biopsy specimens from 11 patients with idiopathic pulmonary fibrosis (IPF) was studied using a 96-well chemotaxis chamber. Fibroblasts from eight normal controls, seven patients with interstitial fibrosis associated with a collagen vascular disease (IP-CVD), and 13 patients with sarcoidosis were also examined. Migratory activity was tested in a serum-free medium in the presence and absence of platelet derived growth factor (PDGF), 30 ng/ml, as a chemoattractant. RESULTS: Migration of fibroblasts from patients with IPF was enhanced in serum-free maintenance medium alone (mean (SD) controls v IPF: 183 (86) v 689 (491) cells/field), and was also enhanced when cells were stimulated by PDGF (controls v IPF: 829 (222) v 1928 (600) cells/field). Fibroblasts from tissues with dense fibrosis had a greater capacity for migration than those from an earlier stage of fibrosis. No correlation was found between migratory activity and proliferative capacity of the individual cells. CONCLUSIONS: The fact that fibroblasts from fibrotic lungs migrate faster than those from controls suggests that migration is related to the initiation of the pulmonary fibrotic process. These in vitro studies suggest that fibroblasts derived from the lungs of patients with pulmonary fibrosis have a migratory phenotype. Such a change in fibroblast phenotype, if it occurred in vivo, may be important in the context of the pathogenesis of pulmonary fibrosis.

Adult↗

Extraction and purification of yellow-fluorescent lipofuscin in rat kidney.

Yellow fluorescent lipofuscin deposited in rat tissues was extracted in an aqueous solution. Yellow fluorescence with fluorescence maxima at 400/615-620 nm was detected in the aqueous extracts of brain and kidney of older rats. Purification and characterization of the yellow fluorescent components extracted from rat kidney were attempted. Centrifugal fractionation of the extract revealed that the flourescence was detected in the 105,000 g supernatant, and not in nuclei, mitochondria, lysosomes, microsomes and cell debris. Gel filtration of the supernatant through Sephadex columns gave at least 5 yellow fluorescent components with different molecular weights. The higher-molecular-weight components were converted into the smaller ones on treatment with alkali or ethanol, but may not be on protease treatment. These components were adherent to polymers composed of sugars. They were soluble in water and not in an organic solvent. While the yellow fluorophores were stable on borohydride treatment, they were destroyed on heavy metal ion treatment. The characteristics of the yellow fluorophores were different from those of bluish lipofuscin-like fluorophores generated by lipid peroxidation.

Aging↗

Analysis of fused-membrane structures in bronchoalveolar lavage fluid from patients with alveolar proteinosis.

Alveolar macrophages of patients with alveolar proteinosis, obtained by lung lavage, contain a large number of intracytoplasmic inclusions with mutlilamellar membranous structures, called fused-membrane structures, having a periodicity of 4.7 nm. To analyze the composition of these structures, we concentrated them from the bronchoalveolar lavage fluid of patients by a combination of sucrose density-gradient ultracentrifugation and enzyme hydrolysis using proteinase K. Fused-membrane structures were most numerous (26.2%) in a fraction obtained at the interface between 1.0 and 1.1 M sucrose solutions separated after proteinase K hydrolysis. This fraction was rich in acidic phospholipids. Hydrophobic surfactant apoproteins constituted about 77% of the proteins in this fraction, and a remarkable increase in the content of surfactant-associated protein C (SP-C) was found. The phospholipid-to-protein ratio was 0.25:1. Based on these results, we tried to reconstitute fused-membrane structures from purified lipids and hydrophobic proteins isolated from the patients' lavage fluid or from pig lungs. Only in the presence of both phospholipids and SP-C were similar multilamellar structures, having a periodicity of 4.3 to 4.5 nm, formed. These results suggest that fused-membrane structures have a close relationship to a hydrophobic surfactant-associated protein, SP-C, which accumulates in alveolar macrophages, possibly by incomplete digestion.

Amino Acid Sequence↗

The influence of ovarian hormones on the granulomatous inflammatory process in the rat lung.

This study was initiated to clarify the relationship between ovarian hormones and the granulomatous inflammatory process in the lung. To assess whether ovarian dysfunction influences the granulomatous inflammatory process, we compared immunological alterations in ovariectomized rats and in sham-operated rats. After a heat-killed, bacilli Calmette-Guérin (BCG)-elicited granulomatous reaction, the lung-body weight ratios, the number of lymphocytes and activated T-cells, and the interferon-gamma levels in the bronchoalveolar lavage fluid from the ovariectomized rats were significantly higher than those of the sham-operated rats. Moreover, exogenous ovarian steroids supplemented in vivo suppressed not only the granulomatous inflammatory process in the lungs, but also the parameters measured in the bronchoalveolar fluid. These results indicate that ovarian dysfunction may adversely affect the formation of granulomas in the lung.

Animals↗

Glucocorticoid receptor expression is down-regulated by Lp(a) lipoprotein in vascular smooth muscle cells.

Glucocorticoids have been reported to protect against atherosclerosis and have been used clinically as protective therapy for restenosis after balloon angioplasty. Recently, Lp(a) lipoprotein [Lp(a)] levels have been suggested to be an independent risk factor for atherosclerosis, although its mechanisms of action are still uncertain. To clarify this atherogenic mechanism of Lp(a), we investigated the effects of Lp(a) on glucocorticoid receptor (GR) expression in human vascular smooth muscle cells (SMC). Levels of nuclear GR in SMC began to decrease after 12-h incubation with Lp(a), to 55 +/- 8% of the control value at 48 h; binding affinity did not change. Lp(a) had no effect on estrogen receptor binding in SMC. Moreover, low, very low, and high density lipoproteins had no effect on GR binding in SMC. The effects of Lp(a) on nuclear GR in rat SMC were very similar to those in human SMC; in contrast, Lp(a) did not alter GR or estrogen receptor levels in rat endothelial cells. GR messenger RNA levels in SMC decreased after 1-h treatment with Lp(a) to 23% of the control value after 12 h. Further, the antiproliferative effect of glucocorticoids on SMC was blunted by exposure to Lp(a). We conclude that Lp(a) down-regulates GR gene expression, resulting in a decreased number of GR in SMC. These findings suggest the possibility of a novel atherogenic mechanism of Lp(a) via inhibition of a protective action of glucocorticoids on SMC.

Aged↗