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Biomedical subjects

Y Murakami

Publications and source records attributed to Y Murakami.

At least 541 records · Page 30Linked to original sources

Inhibition of mucociliary clearance of the eustachian tube by leukotrienes C4 and D4.

The effect of leukotrienes C4 (LTC4) and D4 (LTD4) and prostaglandin E2 (PGE2) on mucociliary clearance of the eustachian tube was investigated in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated separately with LTC4, LTD4, and PGE2 at concentrations of 10(-8) mol/L and 10(-6) mol/L. Ciliary activity was measured photoelectrically. Leukotriene D4 progressively inhibited ciliary activity, while PGE2 promoted it. Leukotriene C4 also induced ciliary inhibition. One milliliter each of 10(-5) mol/L LTC4, LTD4, and PGE2 was directly injected into the tympanic bullae of chinchillas under anesthesia. The middle ears were examined by otomicroscopy, tympanometry, and auditory brain stem response over time. Clearance of middle ear effusion was delayed by LTC4 and LTD4, as compared with PGE2 and the control. These findings indicate that LTC4 and LTD4 inhibit mucociliary clearance of the eustachian tube.

Animals↗

Rarity of oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in Japan.

Constitutively activating mutations have recently been identified in the thyrotropin receptor (TSHR) of hyperfunctioning thyroid adenomas and familial hyperthyroidism. In the present study, we evaluated the frequency of constitutively activating TSHR mutations in a large series of autonomously functioning thyroid nodules (AFTNs) in Japan. Forty-five AFTNs (38 solitary hyperfunctioning thyroid adenomas and 7 toxic multinodular goiters) were analyzed. Genomic DNA was extracted from paraffin-embedded tissue sections, from which DNA fragments encoding the mutational hot spots of the receptor (the third cytoplasmic loop and the sixth transmembrane segment) were amplified by polymerase chain reaction. In the single-stranded conformation polymorphism (SSCP) analysis, only one hyperfunctioning adenoma (no. 21) displayed a migration abnormality. In sequence analysis, an unusual mutation of alternate three-base deletions at nucleotides 1953-1957 (AAA GAT ACC to AAG TCC), resulting in one amino acid deletion (Asp at 619) and one conservative amino acid substitution (Thr to Ser at 620), was identified in tumor DNA but not in leukocyte DNA of no. 21. Further, the normal sequence in these regions was confirmed in 10 randomly selected samples with normal migrating patterns in SSCP analysis. The functional property of the mutant with delta 619 and T620S (designated TSHR delta 619) was then evaluated with in vitro mutagenesis and transfection studies. Unexpectedly, however, there were no significant differences in TSH binding affinity, and basal and TSH-stimulated levels of cAMP and inositol 1,4,5-triphosphate between the TSHR delta 619 and the wt-TSHR. In conclusion, the incidence of the constitutively activating TSHR mutations in AFTNs appears to be low in Japan. The oncogenic potential of a novel somatic mutant TSHR delta 619 identified in a hyperfunctioning adenoma in this study is at present uncertain because of its intact function.

Base Sequence↗

Effects of dietary nucleotides on lipid metabolism and learning ability of rats.

To investigate the effects of dietary nucleotides on lipid metabolism and learning ability, male Sprague-Dawley rats were fed with a nucleotides-supplemented diet or a nucleotides-free diet for 5 weeks. The content of nucleotides in the diet was 1.0% and their composition resembled that in human milk. The content of phosphatidylcholine (PC) and the ratio of PC to phosphatidylethanolamine (PE) in the cerebral cortex of rats fed the nucleotides-supplemented diet were significantly higher than that of rats fed the nucleotides-free diet. However, there was no difference in the content of PC and the ratio of PC to PE in the liver between the two groups. The levels of docosahexaenoic acid (C22:6n-3) and arachidonic acid (C20:4n-6) in the cerebral PC fraction were higher in rats fed the nucleotides-supplemented diet. The learning ability of rats fed the nucleotides-supplemented diet, which was evaluated by the water-filled multiple T-maze test and passive avoidance test, was superior to the of rats fed the nucleotides-free diet. The results presented here suggest that dietary nucleotides may influence lipid metabolism of the cerebral cortex and contribute to the rise in learning ability of rats.

Animals↗

Trehalase activity and trehalose content in a freeze-tolerant yeast, Torulaspora delbrueckii, and its freeze-sensitive mutant.

Two types of trehalase activities different in the optimum reaction pH (4.3 and 6.7) were found in a freeze-tolerant yeast, Torulaspora delbrueckii D2-4, and three types of the activities at pH 4.3, 5.7, and 6.7 were found in its freeze-sensitive mutant (60B3). The pH 4.3 activities in the cell extracts of the two strains were on the same level, but the pH 6.7 activity in the strain D2-4 was about half of that in the strain 60B3. The enzyme with the pH 4.3 activity and the other two enzymes were analogous to acid and neutral trehalases, respectively, in the sensitivity to metal ions and in response to phosphorylation and dephosphorylation. The trehalose content in the strain D2-4 was three times higher than that in the strain 60B3. The change of trehalose content during growth of the strain 60B3 correlated only to the change of the pH 5.7 activity.

Adaptation, Physiological↗

Inhibition of cholera toxin by human milk fractions and sialyllactose.

The effects of human milk fractions on clolera toxin B subunit binding to monosialoganglioside 1 (GM1) were investigated. Human milk, human defatted milk, whey, and a low-molecular-weight fraction of human milk inhibited the binding, but casein did not inhibit it. The inhibitory activity of whey from bovine-milk-based infant formula was less than that of whey from human milk. Differences in composition between human and bovine whey seemed to influence the extent of the inhibitory activity. Sialylated oligosaccharides were considered to be the possible components that inhibited cholera toxin. The effects of sialyllactose, a predominant sialylated component of human milk, on cholera toxin-induced diarrhea were investigated by the rabbit intestinal loop method. Sialyllactose inhibited the cholera toxin inducing fluid accumulation, although neither sialic acid nor lactose had an effect on it. The results suggest that sialyllactose is responsible for the inhibitory activity of milk on cholera toxin.

Animals↗

Young female patient with testosterone-producing adrenocortical adenoma also showing signs of subclinical Cushing's syndrome.

A 28-year old female patient with virilization due to left adrenocortical adenoma was studied. The patient had clinical features of hyperandrogenism such as hirsutism and a low pitched voice, but not of hypercorticoidism. Plasma testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were high. Although the basal plasma cortisol concentration and urinary excretion of 17-hydroxycorticosteroids (17-OHCS) were within the normal range, the absence of diurnal variation in plasma cortisol and loss of suppressibility by dexamethasone suggested constitutive secretion of cortisol by the tumor. Inappropriate cortisol secretion was also supported by blunted ACTH response to provocative stimuli. After successful removal of the left adrenal tumor, such endocrinological abnormalities were all normalized. Immunohistochemical analysis revealed that tumor cells were positively stained for C21 hydroxylase cytochrome P-450 (P-450C21) and P-450(11) beta which convert 17-hydroxy (OH) progesterone to cortisol as well as P-450SCC, 3 beta-hydroxysteroid dehydrogenase and P-450(17) alpha which are involved in testosterone biosynthesis. These findings suggest that adrenocortical adenoma secretes predominantly testosterone and constitutively cortisol in a young woman patient with virilization.

17-Hydroxycorticosteroids↗

Serum concentrations of granulocyte colony-stimulating factor (G-CSF) determined by a highly-sensitive chemiluminescent immunoassay during the clinical course of subacute thyroiditis.

Granulocyte colony-stimulating factor (G-CSF) concentrations in serum were determined for the first time by a newly developed and highly sensitive chemiluminescent immunoassay (the limitation of detection, 0.5 pg/ml) in ten patients with subacute thyroiditis, during treatment with glucocorticoid or indomethacin. Before therapy, circulating neurophil counts significantly increased to 5.15 +/- 2.07 x 10(3)/microliters compared with the convalescent phase (2.94 +/- 1.07 x 10(3)/microliters), and the data were correlated with individual serum G-CSF levels (r = 0.854, P < 0.01). Serum concentrations of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were less than the detectable threshold of ELISA. During two weeks of glucocorticoid therapy, although the circulating neutrophil counts increased from 5.15 +/- 2.46 x 10(3)/microliters to 7.73 +/- 1.64 x 10(3)/microliters (P < 0.01), serum G-CSF levels were depressed from 25.1 +/- 15.3 pg/ml to 13.8 +/- 13.9 pg/ml (P < 0.01). These data indicate that G-CSF is one of the mediators of the increase of neutrophils in subacute thyroiditis, while it does not contribute to steroid-induced neutrophilia.

Adult↗

Isolated adrenocorticotropic hormone deficiency associated with growth hormone deficiency and empty sella.

A 38-year-old man had an acute onset of consciousness loss, pyrexia and hyponatremia. Plasma Adrenocorticotropic Hormone (ACTH) and cortisol levels were low. Plasma ACTH failed to respond to corticotropin-releasing hormone (CRH) and insulin-induced hypoglycemia whereas i.m. injection of ACTH-Z raised plasma cortisol. Plasma insulin-like growth factor-I (IGF-I) and urine growth hormone (GH) concentrations were also low and plasma thyroid-stimulating hormone (TSH) level was rather elevated. Plasma IGF-I and TSH levels were not completely normalized by glucocorticoid (GC) replacement alone although plasma GH responses to pharmacological stimuli were normalized. The GC replacement in combination with daily s.c. injection of recombinant human GH (rhGH) not only normalized plasma IGF-I and IGFBP-3 levels, but also further lowered the plasma TSH level, possibly due to an increased T4/T3 conversion, which resulted in a beneficial change in body composition.

Adrenocorticotropic Hormone↗

Generation of 28 sequence-tagged sites (STSs) from yeast artificial chromosome (YAC) clones anchored at human chromosome 21q22.1 region.

Twenty-eight sequence-tagged sites (STSs) were newly generated from the DNA sequences of vector-insert junctions from yeast artificial chromosomes (YACs) anchored at chromosome 21q22.1 region. The insert DNAs adjacent to vector arms were specifically amplified through inverse PCR method to clone into pUC19 vector for sequencing. Sixty DNA junctions from 44 CEPH YAC clones were cloned and sequenced. Of these DNA sequences of junctions between vector-arms and DNA inserts, twenty-eight STSs were finally obtained to show the accurate amplification, which is specific for human chromosome 21. The sets of 28 STSs were useful to build fine YAC contigs by STS-mediated YAC walking at the 21q22.1 region.

Animals↗

[Relationship between orthostatic dizziness and/or giddiness, and hypotension in young normal females--a survey of 301 subjects].

Orthostatic dysregulation (OD) generally implies a systemic condition indicating poor circulatory function resulting from autonomic imbalance. It frequently appears in younger individuals at or around puberty, and is predominant in females. It is also known that individuals with this condition experience orthostatic dizziness and/or giddiness, fainting on standing and other various non-specific, subjective symptoms. Three hundred and one young normal females ranging in age from 18 to 21 years were examined using the Schellong test and the OD questionnaire to investigate the relationship between orthostatic dizziness and hypotension. Orthostatic dizziness and/or giddiness was the most frequent symptom, noted in 171 of 301 young subjects (56.8%), regardless of whether or not the subjects were actually diagnosed as having OD based on the questionnaire. Both low systolic blood pressure (90 mmHg or loss) in the supine position and systolic pressure decrease (11 mmHg or more) in the standing position during the procedure for the Schellong test were significantly related to the occurrence of orthostatic dizziness and/or giddiness. It may be reasonable to conclude from the present study that orthostatic dizziness is even more commonly observed in young normal female subjects than expected and correlates more closely with both hypotension and systolic pressure decrease in the standing position than previously thought. Thus, in our opinion, this testing procedure introduced by Schellong can be useful, and is clinically applicable to the assessment of orthostatic dizziness and/or giddiness and OD, since this test has the advantage of being simple enough to carry out in clinical practice.

Adolescent↗

Prevention of anti-T-cell receptor alpha beta monoclonal antibody-induced side-effects by treatment with cyclosporin A without interference of monoclonal antibody-induced immunosuppression in mice.

Anti-T-cell receptor (TCR)alpha beta monoclonal antibody (mAb; H57-597) injection in mice caused cytokine (tumour necrosis factor and interferon-gamma) release and clinical side-effects such as piloerection and body weight loss similar to anti-CD3 mAb (145-2C11) injection. Treatment with cyclosporin A (CsA) for 3 days, from day -2 to day 0, prior to anti-TCR alpha beta mAb injection almost completely abolished the mAb-induced cytokine release, and completely inhibited the mAb-induced body weight loss. Furthermore, treatment with CsA from day -2 to day 0 did not inhibit the mAb-induced in vivo immunosuppressive effects, i.e. prolongation of skin allograft and T-cell depletion in the periphery. These results indicate that CsA treatment prior to mAb treatment could effectively inhibit the mAb-induced side-effects without interference of the mAb-induced in vivo immunosuppression. From these results, we propose that CsA treatment prior to injection of anti-TCR alpha beta mAb may be recommended to reduce mAb-induced side-effects.

Animals↗

Effect of ibudilast on ciliary activity of human paranasal sinus mucosa in vitro.

The effect of ibudilast (CAS 50847-11-5, 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine, KC-404), an anti-asthmatic drug, on ciliary beat frequency (CBF) of human paranasal sinus mucosa was examined in vitro. Ciliary activation was observed after a 10-min exposure to 4.6 x 10(-6) mol/l ibudilast. Ibudilast dose-dependently increase CBF at the concentrations ranging from 4.6 x 10(-7) mol/l to 4.6 x 10(-5) mol/l. Propranolol inhibited ciliary activity induced by ibudilast; however, neither indometacin nor verapamil affected the activation of ibudilast on CBF. Platelet activating factor (PAF) and Leukotriene D4 (LTD4) are chemical mediators inducing mucosal dysfunction and damage. Ibudilast prevented ciliary inhibition induced by PAF and LTD4. These findings indicated that ibudilast activates CBF and inhibits the effect of PAF and LTD4 on ciliated cells, and consequently improves the pathogenesis of allergic disorders such as the inhibited mucociliary transport system and airway hyperresponsiveness.

Bronchodilator Agents↗

Mac-1 expression and superoxide generation of the peripheral polymorphonuclear leukocyte following gastrectomy and esophagectomy.

The aim of this study was to evaluate the characteristics of the polymorphonuclear leukocyte (PMN) function after surgical stress. We investigated Mac-1 expression and superoxide generation by peripheral PMNs and serum granulocyte-colony stimulating factor (G-CSF) concentrations in 15 patients who underwent either gastrectomy (n = 8) or esophagectomy (n = 7). The serum G-CSF rapidly increased within 24 hours after operation. The maximum levels of serum G-CSF in the cases of esophagectomy were about 5-8 fold those of gastrectomy, although the increases in PMN counts within 24 hours of esophagectomy were lower than those after gastrectomy. Mac-1 expression and superoxide generation by PMN counts and serum G-CSF. After esophagectomy, Mac-1 expression on peripheral PMNs remained elevated through the 7th day after operation, while superoxide generation by PMNs in response to PMA declined to below preoperative levels after the 3rd day. These results suggest that, after major surgery such as esophagectomy, there is a discrepancy between Mac-1 expression and superoxide generation by the peripheral PMN despite a high level of serum G-CSF.

Aged↗

[A case of bilateral partial anomalous pulmonary venous connections with the right upper pulmonary vein draining to the high superior vena cava].

A 10-year-old girl with bilateral partial anomalous pulmonary venous connections (PAPVC) was referred to us. The right upper pulmonary vein (PV) drained to the high superior vena cava (SVC) and the left upper PV to the left innominate vein. The left upper PV was directly anastomosed to the right atrial appendage. The SVC was divided distal to the orifice of the right upper PV and anastomosed to the right atrial appendage. A Xenomedica patch was placed within the right atrium to divert the pulmonary venous blood from the SVC orifice across the surgically enlarged ASD to the left atrium. The postoperative course was satisfactory without arrhythmia, and cineangiography revealed no obstruction at the SVC and the right upper PV pathways. We thought that this method is advantageous in preserving the sinus node and its feeding artery, as well as being applicable to the PAPVC to the high SVC.

Anastomosis, Surgical↗

An autopsy case of B-cell lymphoma associated with macroglobulinemia (IgM-k).

While he was treated for macroglobulinemia showing symptoms, a 65-year-old man developed an enlargement of the left lateral cervical lymph node. Biopsy specimens of the cervical lymph node revealed large-cell non-Hodgkin's lymphoma. The lymphoma cells had rearrangement in the immunoglobulin heavy chain and kappa light chain genes. There was osteolysis involving right metatarsal bones. And, a tumor appeared on the upper hard palate in the terminal stage. Autopsy specimens showed infiltration of lymphoma cells into multiple organs. Production of monoclonal immunoglobulin M was detected only slightly and focally in the tumors. Plasmacytic differentiation as in Waldenström's macroglobulinemia was not seen in any organs except the tumor on the upper hard palate. From these findings, it is speculated that B-cell lymphoma might have developed in the course of macroglobulinemia.

Aged↗

[Two diabetics with hemichorea-hemiballism and striatal lesions].

We report two diabetic patients with hemichorea-hemiballism associated with striatal lesions detected by MRI. Case 1 was a 57-year-old woman. On May 5, 1990, hemichorea-hemiballism of the right upper extremity developed suddenly. The blood glucose level at the time of onset was 695 mg/dl. Plain cranial CT scanning revealed a small high-density lesion in the left putamen. On MRI, this lesion showed a high signal intensity on T1-weighted images, while it showed as an irregular low-intensity area on T2-weighted images. Three and a half months later, the high intensity lesion on MRI decreased gradually and almost disappeared. Case 2 was a 68-year-old woman. In late August 1992, hemichorea-hemiballism of the right upper and lower extremities developed suddenly. The blood glucose level at the time of onset was 365 mg/dl. Plain cranial CT scanning was normal. MRI revealed a high signal intensity lesion involving the left putamen, globus pallidus and head of the caudate nucleus on T1-weighted images, while the lesion was almost isointense on T2-weighted images. The high-intensity lesion on MRI thereafter decreased gradually and disappeared almost completely one year after the onset. It is characteristic that the lesions responsible for hemichorea-hemiballism showed high-intensity areas on T1-weighted MRI in these two diabetics. In the hyperglycemic state, the Krebs cycle is inhibited and GABA is utilized as an energy source. The possibility has been suggested that striatal ischemia is likely to occur in diabetics because the GABA content of the corpus striatum is decreased by hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Atrial late potential (ALP) by P wave-triggered signal-averaged electrocardiogram].

Late potentials, possibly representing fractionated electrograms recorded directly from slowly conducting cardiac tissue, can be detected by signal averaged ECG (SAECG) from the body surface noninvasively. Ventricular late potential, recorded with SAECG, is a good predictor of ventricular tachyarrhythmias. Analogously, SAECG triggered by P wave has recently been proposed determining atrial late potential (ALP), possibly related paroxysmal atrial fibrillation. ALP is analyzed by the time domain or frequency domain method. In the former, the prolongation of filtered P duration is an index of ALP. The results obtained by FFT analysis in the latter are controversial, and thus additional study will be required to confirm their meaning and significance.

Atrial Fibrillation↗