[A trial for automated laboratory data classification of protein fraction data].
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Data Interpretation, Statistical↗
Biomedical subjects
T Usui
Publications and source records attributed to T Usui.
[Clinical features of acute obstructive suppurative cholangitis (AOSC) in the old age].
Nineteen cases (male 6, female 13) of acute obstructive suppurative cholangitis (AOSC) were divided into 2 groups and were studied, Group A; over 70 yrs old (12), Group B; under 70 yrs old (7). The most frequent etiology of AOSC was choledocholithiasis (Group A 75%, Group B 43%). Urgent biliary drainage was performed in 18 cases, and which were clinically improved. The decreasing rate of bilirubin were fair in both groups and only 2 cases in Group A were dead. Concerning with the laboratory findings on admission, Group A had a higher level of BUN than Group B, and there were no other significant differences. Complications were frequently occurred in Group A (Shock 83%, DIC 83%, Renal failure 42%). The diameter of choledochus at biliary drainage was below 9 mm in 45% of cases in Group A, which implied the rapid progression to AOSC from the onset of biliary obstruction. Early diagnosis and urgent biliary drainage were essential for the management of AOSC in the old age.
Acute Disease↗
Transformations of unsaturated acyclic sugars into enantiomerically pure norbornene derivatives.
The C7 acyclic unsaturated-sugar ester 1, derived from L-arabinose, and its enantiomer serve as convenient dieneophiles for chirality transfer for synthesis of optically pure carbocyclic derivatives through cycloaddition reactions. Reaction of 1 with cyclopentadiene may be controlled to give preparative access to the 5,6-disubstituted norbornene adducts 4a, 5a, and 7a, according to the conditions used. The distribution of the four possible isomeric products from this cycloaddition was quantitated, and the effect of substitutional variation on the precursor dienophile 1 was also examined. Adducts 4a and 5a were transformed into such substituted carbocycles of known absolute configuration as the methyl esters (11 and 12) of norbornene (bicyclo[2.2.1]hept-2-ene)-6-carboxylic acid and nortricyclane (tricyclo[2.2.1.0(2,6)]heptane)-3-carboxy acid in optically pure form, specifically through decarbonylation reactions using RhCl(PPh3)3 (Wilkinson's complex) and [Rh(dppp)2]Cl[dppp = Ph2P(CH2)3PPh2]. The optical purity of 12 was established by the use of a chiral lanthanide shift-reagent.
Carbohydrate Conformation↗
Synthesis of optically pure di- to tetra-substituted cyclopentanes from sugar-derived norbornene derivatives.
The chiral norbornene derivative 2 obtained from Lewis acid-catalyzed reaction of an L-arabinose-derived dienophile 1 and cyclopentadiene was oxidized with OsO4-NaIO4 to the dialdehyde 3, a tetrasubstituted cyclopentane. Mild treatment of 3 with [Rh(dppp)2]Cl [dppp = Ph2P(CH2)3PPh2] (4) selectively epimerized the aldehyde adjacent to the methoxycarbonyl group to give the epi-aldehyde 8. Under more vigorous conditions, this group was decarbonylated to give the monoaldehyde 11, and more strenuous treatment removed the second aldehyde group to give the didecarbonylated cyclopentane derivative 5. The structure and optical purity of 5 was confirmed by its transformation into (1S,2S)-cyclopentane-1,2-dicarboxylic acid (7).
Carbohydrates↗
12S-hydroxyeicosatetraenoic acid plays a central role in the regulation of platelet activation.
When platelets are activated by the recognition of exposed collagen fibers, they start synthesizing two major arachidonic acid metabolites, i.e. thromboxane A2 and 12S-hydroxyeicosatetraenoic acid (12-HETE) via cyclooxygenase and 12-lipoxygenase pathways, respectively. Although the physiological role of the former is well established, that of the latter has not been fully elucidated. Recently, we have revealed that 12-HETE interferes with collagen-induced platelet aggregation [Sekiya, F. et al. (1990) Biochim. Biophys. Acta 1044, 165-168]. In the present paper, we show that this substance enhances thrombin-induced aggregation of bovine platelets, in sharp contrast with the case of collagen. Additionally, 12-HETE is able to prevent the prostaglandin E1-induced elevation of platelet cAMP level and counteracts its inhibitory effect on platelet aggregations. With these observations, we propose a novel self-regulatory mechanism of platelets where 12-HETE plays a key role; it switches sensitivity of platelets from the primary agonist (collagen) to the secondary one (thrombin), and cancels the inhibitory effect of cAMP elevators.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Maltotetraose-forming, amylase-mediated, p-nitrophenyl alpha- and beta-maltopentaoside formation in an aqueous-organic solvent system: a substrate for human amylase in serum.
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Amylases↗
Immunological detection of propolypeptide of von Willebrand factor on platelet surface.
Recently we have found that propolypeptide of von Willebrand factor (pp-vWF) obtained from platelets binds to type I collagen. It is known that pp-vWF is present in platelet alpha-granules and is secreted upon activation. In this paper, we demonstrate the two following evidences to show that it is also present on the surface of resting platelets. [1] The antibody against pp-vWF bound to the surface of platelets. [2] The antibody induced aggregation of platelets. The binding of the antibody and the antibody-induced aggregation of platelets were inhibited in a dose-dependent manner by Fab fragment of the antibody. Platelets from von Willebrand disease patients bound less of the antibody and responded weakly to the antibody.
Antibodies↗
Late-infantile type galactosialidosis. Histopathology of the retina and optic nerve.
We studied histopathologic findings from the retina and optic nerve of a patient with the late-infantile type of galactosialidosis and related them to clinical features of the condition. Markedly fewer ganglion cells were evident histopathologically using light microscopy. Results of histochemical studies demonstrated abnormal accumulation of lipid and proteinaceous material in the residual swollen ganglion cells. Marked loss of myelinated nerve fibers and thickening of the pial septum were also observed in the optic nerve. Both retinal ganglion cells and amacrine cells had intracytoplasmic inclusion bodies, but none were found in the optic nerve. These findings suggested that optic atrophy was induced by axonal wallerian degeneration secondary to retinal ganglion cell death. Although the fundus showed advanced optic nerve atrophy, a cherry red spot was not evident, possibly because of the marked decrease in ganglion cells in this case.
Adolescent↗
Role of cyclic AMP and polypeptide growth regulators in growth inhibition by interferon in PC-3 cells.
Participation of growth factors and intracellular cAMP in direct antiproliferative action of interferon alpha (IFN-alpha) was investigated in PC-3 human prostate carcinoma cell line. IFN-alpha inhibited proliferation of PC-3 cells in a dose-dependent manner in vitro, and the effect was reversible. Fibroblast growth factor, epidermal growth factor and platelet-derived growth factor, when added to the culture medium, showed no effect on growth of PC-3 cells in presence or absence of IFN-alpha. Transforming growth factor beta (TGF-beta) significantly inhibited PC-3 cell growth, and the effect was additived to that of IFN-alpha. TGF-beta content in conditioned medium of PC-3 cells was not affected by treatment with IFN-alpha. On the other hand, IFN-alpha increased intracellular cAMP concentration about 20-fold. Dibutyryl cAMP and reagents which elevated intracellular cAMP level also inhibited PC-3 cell growth. These indicated that direct antiproliferative effect of IFN-alpha on PC-3 cells was at least partly mediated by cAMP, and that neither growth factors nor a growth inhibitor participated in the action of IFN-alpha.
Alprostadil↗
Highly synchronous culture of fibroblasts from G2 block caused by staurosporine, a potent inhibitor of protein kinases.
The effect of staurosporine, a potent microbial inhibitor of protein kinases, on the cell cycle of cultured fibroblast cells was investigated. A low concentration of staurosporine (1-10 ng/ml) blocked the cell cycle of rat 3Y1 fibroblasts at the early G1 phase within 2 h after serum stimulation. On the other hand, a higher concentration of the drug (100 ng/ml) caused the specific G2 block. Both of these blocks were reversible. After release from the G2 block, highly synchronous transition to M phase was observed and both nuclear and cell divisions were completed within 180 min. This reversible G2 block showed a clear contrast to those by the other G2 arresters, trichostatin A and leptomycin B, which formed proliferative tetraploid cells after release by entering the cells into a new S phase without passage through M phase. The presence of trichostatin A or leptomycin B did not interfere with this synchronous progression through G2/M phases, suggesting that the arrest point of staurosporine was present in late G2 phase following those of trichostatin A and leptomycin B.
Alkaloids↗
Molecular mechanisms of glucocorticoid inhibition of human proopiomelanocortin gene transcription.
The gene encoding proopiomelanocortin(POMC) offers an interesting model for negative regulation of gene transcription by glucocorticoids. A fragment of human genomic DNA containing the entire POMC gene, together with the neo marker gene, was introduced by transfection into the ACTH-producing mouse pituitary tumor cell line, AtT-20, and the mouse fibroblast L cell line. In the transformed AtT-20 cells the human POMC gene was transcribed correctly and the transcript was spliced faithfully. Furthermore, the addition of dexamethasone to the transformed AtT-20 cells resulted in a 40% reduction of the human POMC mRNA levels. Deletion analysis demonstrated that no more than 417 bp in the 5'-flanking region of the human POMC gene are required for transcriptional repression by glucocorticoid. This region was also responsible for the transcription induction of the human POMC gene by cyclic AMP (cAMP). In the transformed L cells, however, most of the transcripts of the human POMC gene were not correctly initiated. The addition of dexamethasone to the transformed L cells did not significantly affect the content of human POMC mRNA, although these cells expressed glucocorticoid receptor(GR). However, the increase of the transcripts by forskolin, a post-receptor adenylate cyclase-activating agent, was partially but significantly suppressed by dexamethasone in the transformed L cells. These results suggest that binding of GR to the negative glucocorticoid response element (nGRE) could lead to steric occlusion of positive transcription factors, such as cAMP-response element binding protein and tissue specific factors or that GR bound to nGRE could interact with DNA-bound positive factors in such a way as to prevent their transcriptional stimulatory activity.
Animals↗
Effects of chronic bromocriptine-induced hypoprolactinemia on plasma testosterone responses to human chorionic gonadotropin stimulation in normal men.
To study the role played by normal levels of plasma prolactin (PRL) in the secretion of testosterone (T) in the testes, we induced hypoprolactinemia with a daily dose of 5 mg bromocriptine administered orally in five normal men 20 to 35 years of age for 8 weeks. The basal PRL, T, luteinizing hormone, follicle-stimulating hormone, and maximum responses of plasma T to human chorionic gonadotropin (hCG) stimulation were measured every 2 weeks. Basal levels of plasma T were reduced in the 1st 2-week-long period of hypoprolactinemia. In the 4-week-long period of hypoprolactinemia, the maximal response of plasma T to hCG stimulation was significantly reduced. The findings suggest that normal levels of plasma PRL may play an important role in the secretion of T in the human testes in vivo.
Adult↗
Uncoupled cell cycle without mitosis induced by a protein kinase inhibitor, K-252a.
The staurosporine analogues, K-252a and RK-286C, were found to cause DNA re-replication in rat diploid fibroblasts (3Y1) without an intervening mitosis, producing tetraploid cells. Analysis of cells synchronized in early S phase in the presence of K-252a revealed that initiation of the second S phase required a lag period of 8 h after completion of the previous S phase. Reinitiation of DNA synthesis was inhibited by cycloheximide, actinomycin D, and serum deprivation, but not by Colcemid, suggesting that a functional G1 phase dependent on de novo synthesis of protein and RNA is essential for entry into the next S phase. In a src-transformed 3Y1 cell line, as well as other cell lines, giant cells containing polyploid nuclei with DNA contents of 16C to 32C were produced by continuous treatment with K-252a, indicating that the agent induced several rounds of the incomplete cell cycle without mitosis. Although the effective concentration of K-252a did not cause significant inhibition of affinity-purified p34cdc2 protein kinase activity in vitro, in vivo the full activation of p34cdc2 kinase during the G2/M was blocked by K-252a. On the other hand, the cyclic fluctuation of partially activated p34cdc2 kinase activity peaking in S phase still continued. These results suggest that a putative protein kinase(s) sensitive to K-252a plays an important role in the mechanism for preventing over-replication after completion of previous DNA synthesis. They also suggest that a periodic activation of p34cdc2 is required for S phases in the cell cycle without mitosis.
Animals↗
Pharmacological properties of YM-21095, a potent and highly specific renin inhibitor.
A novel renin inhibitor, YM-21095 [2RS), (3S)-3-[N alpha-[1,4-dioxo-4-morpholino-2-(1-naphthylmethyl)-buthyl]-L- histidil-amino]-4-cyclohexyl-1-[(1-methyl-5-tetrazolyl)thio]-2-but anol), has been synthesized in our laboratories. The aim of this study was to evaluate the pharmacological properties of YM-21095 in in vitro and in vivo experiments. YM-21095 inhibited human renin with an IC50 value of 4.7 x 10(-10) mol/L. YM-21095 was also a potent inhibitor against squirrel monkey renin, but less effective against renins from dog, rabbit, and rat. The effect of YM-21095 is highly specific for renin, since it did not inhibit cathepsin D, pepsin, or angiotensin converting enzyme up to a concentration of 10(-4) mol/L. YM-21095 was resistant to proteolytic actions of the enzymes (pepsin, chymotrypsin, trypsin) and squirrel monkey tissue homogenates (liver, kidney, small intestine). Intravenous infusion of YM-21095 (0.1 to 100 micrograms/kg/min) decreased mean blood pressure and inhibited plasma renin activity in a dose-dependent manner with no effect on heart rate in anesthetized sodium-depleted and sodium-replete squirrel monkeys. The hypotensive effect of YM-21095 in sodium-depleted squirrel monkeys was about ten times as potent as that in sodium-replete squirrel monkeys. Oral administration of YM-21095 to conscious sodium-depleted squirrel monkeys produced dose-related decreases of systolic blood pressure. We conclude that YM-21095 is a potent and highly specific inhibitor of primate renin and produces a blood pressure lowering effect.
Administration, Oral↗
Relationship between diastolic mitral regurgitation and PQ intervals or cardiac function in patients implanted with DDD pacemakers.
Diastolic mitral regurgitation (MR) is known to be induced by prolonging atrioventricular (AV) delay in patients implanted with a DDD pacemaker. We studied the relationship between diastolic MR and PQ intervals on cardiac function in 50 patients (71.3 +/- 11.3 years old: mean +/- SD), who had been implanted with DDD pacemakers. In 19 patients, prior to pacemaker implantation, pulmonary capillary wedge pressure (PCWP) was measured using a Swan-Ganz catheter during AV sequential pacing with an AV delay of 0.165 seconds. Transmitral blood flow was measured with pulsed Doppler echocardiography, while prolonging AV delay stepwise by 0.025 seconds from 0.065 seconds for about 5 minutes each. In nine patients, AV delay could not be prolonged enough due to occurrence of intrinsic AV conduction. In the other 41 patients, diastolic MR was induced by prolonging AV delay. The critical PQ intervals that induced diastolic MR ranged from 0.14 to 0.26 (0.23 +/- 0.03) seconds. Four of five patients whose critical PQ intervals were 0.20 seconds or shorter had heart failure, while 36 patients whose critical PQ intervals were greater than 0.20 seconds were free from signs and symptoms of heart failure. Their PCWPs were 2-27 (7.5 +/- 5.1) mmHg. There was a significant negative correlation between the critical PQ intervals for the appearance of diastolic MR and PCWP during AV sequential pacing, which was performed prior to pacemaker implantation (r = -0.85, P less than 0.001). It is suggested that the appearance of diastolic MR is determined mainly by PQ intervals and cardiac function.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Prevalence of antibody to Chlamydia pneumoniae TWAR in japan.
Chlamydia pneumoniae TWAR is a newly recognized Chlamydia species that is a pathogen of respiratory tract infection. To clarify the endemic status of C. pneumoniae in Japan, we evaluated the incidence of C. pneumoniae antibody in 1,330 serum samples (660 from outpatients, 600 from normal individuals, and 70 from cord blood). The antibody titer was determined by a microimmunofluorescence test by using the elementary body of C. pneumoniae TW-183 as the antigen. Immunoglobulin G antibody titers of 1:32 or higher were regarded as evidence of past infection. The detection rate of C. pneumoniae antibody rapidly increased in subjects between the ages of 4 and 7 years, reached 44% in subjects between the ages of 8 and 11 years, and was about 50% in older subjects. The rate did not differ between healthy subjects and outpatients. These results suggest that C. pneumoniae infection is highly endemic in Japan as it is in Western countries. However, the antibody prevalence was high in the low age groups in Japan compared with that in Western countries.
Adolescent↗
Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese.
We studied the prevalence of migraine in low-tension glaucoma (LTG) and primary open-angle glaucoma (POAG). Seventy seven Japanese patients with LTG, 73 with POAG, and 75 normal subjects were randomly selected and tested with a headache questionnaire. The prevalence of headache with or without typical migrainous features (unilateral headache or ocular pain, nausea, vomiting, and visual disturbance before headache) was 51% in LTG, 42% in POAG, and 44% in normal patients. The prevalence of headache with two migrainous features or more (probable migraine) was 17% in LTG, 11% in POAG, and 12% in normal subjects. The prevalence of headache with three migrainous features (classical migraine) was 5% in LTG, 3% in POAG, and 3% in normal subjects. There was no statistically significant difference in the prevalence of any types of migraine between the three groups of patients (p greater than 0.05). These results suggest there is no significant relationship between migraine and LTG or POAG in Japanese patients.
Adult↗
In vitro susceptibility of Ureaplasma urealyticum clinical isolates to new macrolides.
Nine antimicrobial agents, the new macrolides, rokitamycin and midecamycin acetate, and seven other antibiotics, tetracycline, minocycline, doxycycline, josamycin, erythromycin, spiramycin, and norfloxacin, were studied for their antimicrobial activity against 100 strains of Ureaplasma urealyticum, using a microtiter broth dilution technique. The new macrolides, rokitamycin and midecamycin acetate, had the highest activity, with the MIC against 90% of isolates tested (MIC90) being less than or equal to 0.05 microgram/ml. MICs90 of erythromycin, josamycin, doxycycline, minocycline and tetracycline ranged from 0.1 to 0.78 micrograms/ml. Norfloxacin was least active, with a MIC90 of 12.5 micrograms/ml. Five of 100 strains tested were resistant (MIC greater than or equal to 12.5 micrograms/ml) to tetracycline, and two were resistant to minocycline and doxycycline; all of these were susceptible to rokitamycin and midecamycin acetate.
Drug Resistance, Microbial↗