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Biomedical subjects

N Yokota

Publications and source records attributed to N Yokota.

At least 73 records · Page 4Linked to original sources

A novel outer membrane lipoprotein, LolB (HemM), involved in the LolA (p20)-dependent localization of lipoproteins to the outer membrane of Escherichia coli.

The Escherichia coli major outer membrane lipoprotein (Lpp) is released from the inner membrane into the periplasm as a complex with a carrier protein, LolA (p20), and is then specifically incorporated into the outer membrane. An outer membrane protein playing a critical role in Lpp incorporation was identified, and partial amino acid sequences of the protein, named LolB, were identical to those of HemM, which has been suggested to play a role in 5-aminolevulinic acid synthesis in the cytosol. In contrast to this suggested role, the deduced amino acid sequence of HemM implied that the gene encodes a novel outer membrane lipoprotein. Indeed, an antibody raised against highly purified LolB revealed its outer membrane localization, and inhibited in vitro Lpp incorporation into the outer membrane. Furthermore, LolB was found to be synthesized as a precursor with a signal sequence and then processed to a lipid-modified mature form. An E.coli strain possessing chromosomal hemM under the control of the lac promoter-operator required IPTG for growth, indicating that hemM (lolB) is an essential gene. Outer membrane prepared from LolB-depleted cells did not incorporate Lpp. When the Lpp-LolA complex was incubated with a water-soluble LolB derivative, Lpp was transferred from LolA to LolB. Based on these results, the outer membrane localization pathway for E.coli lipoprotein is discussed with respect to the functions of LolA and LolB.

Amino Acid Sequence↗

Effect of dantrolene on KCl- or NMDA-induced intracellular Ca2+ changes and spontaneous Ca2+ oscillation in cultured rat frontal cortical neurons.

Dantrolene has been known to affect intracellular Ca2+ concentration ([Ca2+]i) by inhibiting Ca2+ release from intracellular stores in cultured neurons. We were interested in examining this property of dantrolene in influencing the [Ca2+]i affected by the NMDA receptor ligands, KCl, L-type Ca2+ channel blocker nifedipine, and two other intracellular Ca2(+)-mobilizing agents caffeine and bradykinin. Effect of dantrolene on the spontaneous oscillation of [Ca2+]i was also examined. Dantrolene in microM concentrations dose-dependently inhibited the increase in [Ca2+]i elicited by NMDA and KCl. AP-5, MK-801 (NMDA antagonists), and nifedipine respectively reduced the NMDA and KCl-induced increase in [Ca2+]i. Dantrolene, added to the buffer solution together with the antagonists or nifedipine, caused a further reduction in [Ca2+]i to a degree similar to that seen with dantrolene alone inhibiting the increase in [Ca2+]i caused by NMDA or KCl. At 30 microM, dantrolene partially inhibited caffeine-induced increase in [Ca2+]i whereas it has no effect on the bradykinin-induced change in [Ca2+]i. The spontaneous oscillation of [Ca2+]i in frontal cortical neurons was reduced both in amplitude and in base line concentration in the presence of 10 microM dantrolene. Our results indicate that dantrolene's mobilizing effects on intracellular Ca2+ stores operate independently from the influxed Ca2+ and that a component of the apparent increase in [Ca2+]i elicited by NMDA or KCl represents a dantrolene-sensitive Ca2+ release from intracellular stores. Results also suggest that dantrolene does not affect the IP3-gated release of intracellular Ca2+ and that the spontaneous Ca2+ oscillation is, at least partially, under the control of Ca2+ mobilization from internal stores.

Animals↗

Chronic treatment with antidepressants, verapamil, or lithium inhibits the serotonin-induced intracellular calcium response in individual C6 rat glioma cells.

The effects of chronic treatment with antidepressants, verapamil, or lithium on serotonin (5-HT)-induced Ca2+ increase were investigated in single C6BU-1 glioma cells with digital imaging microscopy. Clomipramine and citalopram, at a concentration of 100 nM, decreased the peak values of 5-HT-induced [Ca2+]i changes. Verapamil (100 nM), a calcium antagonist, and lithium (1 mM) also inhibited the peak amplitudes in the same way. The present findings suggest that chronic treatment with antidepressants, verapamil, or lithium, at therapeutic concentrations, have the common action of inhibiting 5-HT-mediated [Ca2+]i increase.

Animals↗

Urine and plasma levels of uroguanylin and its molecular forms in renal diseases.

Uroguanylin activates the intestinal and possibly the renal guanylate cyclase C receptor, and stimulates Cl- secretion. We developed a sensitive radioimmunoassay (RIA) for human uroguanylin and measured its concentration in the urine and plasma. Twenty-four-hour urinary excretion of immunoreactive (ir-) uroguanylin for persons with a high-salt diet (10 g/day) was 137.8 +/- 14.4 pmol/day, significantly higher than that for persons with a low-salt diet (7 g/day, 95.1 +/- 16.3 pmol/day, P < 0.05). There were significantly positive correlations between the urinary excretion of ir-uroguanylin and Na+, Cl-, K+ or cyclic GMP (cGMP). We demonstrated the presence of messenger RNA of guanylate cyclase C in the medulla of human kidney. The concentration of plasma ir-uroguanylin significantly correlated with that of serum creatinine (r = 0.71, P < 0.001). Biologically active uroguanylin-16 accounted for 99% of the endogenous uroguanylin molecules in normal urine and 60% in plasma, the remainder being the 10 kDa precursor. The precursor content increased in the urine and plasma as the severity of renal impairment increased. These findings suggest that bioactive uroguanylin-16 is involved in the regulation of electrolyte homeostasis and that the kidney participates in the metabolism and excretion of uroguanylin.

Circadian Rhythm↗

Benefits of trazodone and mianserin for patients with late-life chronic schizophrenia and tardive dyskinesia: an add-on, double-blind, placebo-controlled study.

The objective of the present study was to evaluate the efficacy of mianserin and trazodone as antidepressants with serotonin 2 antagonist properties on negative symptoms and tardive dyskinesia in elderly patients with chronic schizophrenia. In this double-blind, placebo-controlled study the dose of each drug was increased gradually, from 20 mg/day mianserin to 60 mg/day, and from 50 mg/day trazodone to 200 mg/day. Symptoms were assessed using the Brief Psychiatric Rating Scale, the Scale for Assessment of Negative Symptoms and the Abnormal Involuntary Movement Scale every week for 5 weeks. A total of 38 patients (23 men and 15 women) completed the trial. Mianserin (n = 13) and trazodone (n = 12) did not alter the Brief Psychiatric Rating Scale positive symptom factor over the 5 weeks. In the mianserin group, the Scale for Assessment of Negative Symptoms total score decreased significantly after 5 weeks. Scores of 'affective flattening and blunting' and 'alogia' scores on the Scale for assessment of Negative Symptoms decreased significantly in both treatment groups. In the trazodone group, the decrease in the Abnormal Involuntary Movement Scale total score was statistically significant at weeks 2 and 3. Results indicate that serotonergic antidepressants, when used in conjunction with neuroleptics, are safe and effective for treating negative symptoms in elderly patients with chronic schizophrenia. Results also indicated a possible beneficial effect of trazodone in treating tardive dyskinesia.

Age Factors↗

Tissue-specific regulation of renal and cardiac atrial natriuretic factor gene expression in deoxycorticosterone acetate-salt rats.

Atrial natriuretic factor (ANF) is expressed in several noncardiac tissues where it may have an autocrine or paracrine function. Such function may be expected of locally synthesized ANF in the renal parenchyma. Previous investigations of the existence of ANF mRNA in the renal parenchyma have yielded conflicting results. The investigations reported here were designed to detect and measure ANF mRNA in normal rats and in rats subjected to a deoxycorticosterone acetate (DOCA)-salt treatment schedule known to strongly activate cardiac ANF gene expression. The expression of the renal ANF gene was measured using a newly developed quantitative competitive reverse transcription-polymerase chain reaction (QC-RT-PCR). This method uses an internal competitor that serves as an internal standard and makes the procedure independent of measurement relative to housekeeping genes. It was found that renal ANF mRNA levels were 10(7) times lower than those found in left or right atria, but immunoreactive (ir) renal ANF concentration by specific radioimmunoassay was 10(4) times lower than that of atrial irANF levels. Reverse-phase high-performance liquid chromatography analysis revealed that more than 99% of renal irANF is processed ANF(99-126). This finding suggests that most of the irANF measured in kidney extracts likely originates from atrial sources. Left atrial ANF mRNA levels after 1 week of DOCA-salt treatment was significantly higher than that of control rats ([21.06+/-2.99] x 10(-l5) mol/microg total RNAversus [8.59 +/-1.26] x 10(-5) mol/microg total RNA, P<.05). However, renal ANF mRNA levels in DOCA-salt rats were significantly decreased compared with those of control rats ([1.64+/-0.34] x 10(-22) mol/microg total RNA versus [3.96+/-0.61]x 10(-22) mol/microg total RNA, P<.05). These results indicate that (1) renal ANF mRNA can be consistently and specifically demonstrated after reverse transcription and PCR amplification; (2) renal and cardiac ANF synthesis are regulated in a tissue-specific, opposite manner during DOCA-salt treatment; and (3) the finding that renal ANF mRNA is downregulated by DOCA-salt treatment together with previous findings suggest the need for further investigation into the role of renal ANF mRNA downregulation in the pathogenetic mechanism that leads to volume expansion and hypertension after chronic DOCA-salt treatment.

Animals↗

Visual evoked potential guidance for posteroventral pallidotomy in Parkinson's disease.

Visual evoked potentials (VEPs) to photic stimulation of the eyes were used to identify the optic tract and thus determine the location of the globus pallidus internus (GPi) in eight patients with Parkinson's disease who then underwent posteroventral pallidotomy. Distinct waves appeared at 1 or 2 mm below the target (4 to 5 mm below the intercommissural line) and the amplitude significantly increased at 5 or 6 mm below, strongly suggesting that the electrode was in contact with the optic tract. In the medio-lateral direction, potentials were successively recorded in an area of 4 to 8 mm length, indicating the width of the optic tract. The trajectory at the mid point showed the most significant potentials which suggested the center of the optic tract. The site of the first lesion was placed 0 to 2 mm lateral to this trajectory and 5 mm above the point at which the amplitudes of responses increased. The actual lesion site significantly differed from the tentative target in a medio-lateral direction by 1 to 5 mm (mean 3.0 +/- 1.5 mm, n = 6). The Unified Parkinson's Disease Rating Scale score significantly improved and magnetic resonance imaging taken 2 or 3 weeks after the operation showed a lesion within the GPi in each patient. Recording of VEPs greatly facilitates accurate determination of the GPi.

Aged↗

[Objective measurement of motor activity in Parkinson's disease by actigraphy. Clinical assessment of akinesia].

Actigraphy measures physiological activity by using an acceleration sensor and RAM equipped with a data logger. Since actigraphy can continuously and easily record data over a long period of time without disturbing the normal activities of subjects, it is possible to analyze a large number of subjects. Actigraphy was performed in patients with Parkinson's disease who did not exhibit trembling. Results showed that the daily motor activity of patients was lower than that of the healthy individual. Daily motor activity was also found to be correlated with Hoehn-Yahr's classification. Furthermore, side-effects due to L-dopa, such as abnormal involuntary movement and on-off phenomenon, could be objective assessed. The results of long-term actigraphic examination, conducted after anti-Parkinsonian treatment, showed that akinesia improved with time. From these findings, it is concluded that actigraphy could quantitatively assess the degree of akinesia in Parkinsonian patients. Furthermore, actigraphy may be applied to the clinical assessment of drugs.

Antiparkinson Agents↗

Predominant expression of human zic in cerebellar granule cell lineage and medulloblastoma.

Zic is a novel zinc finger protein which displays a highly restricted expression pattern in the adult and developing mouse cerebellum and is highly homologous to the recently cloned Drosophila pair-rule gene Opa. To clarify the mechanism for the development of the human cerebellum and its involvement in human nervous system diseases, we have isolated human Zic cDNA and examined its expression by using monoclonal antibody against recombinant Zic protein. The nucleotide sequence of human Zic cDNA is 85% homologous to that of mouse Zic cDNA. Its putative amino acid sequence is highly conserved (> 99%) except for substitution of only two amino acid residues. In situ chromosome hybridization localized the human Zic gene to chromosome band 3q24. Human Zic protein was immunohistochemically detected in the nuclei of the cerebellar granule cell lineage from the progenitor cells of the external germinal layer to the postmigrated cells of the internal granular layer. Furthermore, Zic protein was detected in medulloblastoma (26/29 cases), whereas no other tumors examined (over 70 cases including primitive neuroectodermal tumors) expressed this protein. These findings suggest that Zic is a potential biomarker for medulloblastoma as well as the human cerebellar granule cell lineage.

Adolescent↗

Effect of interferon-alpha on DOI-induced wet-dog shakes in rats.

Acute (1 h) intraperitoneal (i.p.) treatment with interferon (IFN)-alpha-2a (300 IU/g) significantly inhibited wet-dog shakes (WDS) induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI; 0.5, 1.0 mg/kg), which is mediated by serotonin (5-hydroxytryptamine; 5-HT)2 receptor in rats. IFN-alpha did not affect spontaneous locomotion. The inhibition of DOI (0.5 mg/kg)-induced WDS by IFN-alpha was dose (90-300 IU/g)- and time (1-6 h)-dependent, and was prevented by 30 min pretreatment with naltrexone (NLTX; 1.0 mg/kg, i.p.), an opioid receptor antagonist. Acute (1 h) intracerebroventricular (i.c.v.) treatment with IFN-alpha (1,500 IU/rat) also inhibited DOI (0.5 mg/kg)-induced WDS, and the effect was blocked by NLTX (50 micrograms/rat, i.c.v.). These results suggest that IFN-alpha may modulate 5-HT2 receptor-mediated behavior through opioid receptors in the central nervous system.

Amphetamines↗

Differential regulation of intracellular signaling systems by sodium fluoride in rat glioma cells.

We investigated the rapid and slow effects of NaF on intracellular signaling systems such as Ca2+ homeostasis and cyclic GMP (cGMP) generation in rat glioma C6 cells, using the Ca2+-sensitive dye fura-2 and cGMP enzyme immunoassay. We found that the following: (a) NaF enhanced cGMP generation in a concentration-dependent manner. This enhancement was abolished by pretreatment with 100 microM BAPTA tetraacetoxymethal ester or in the presence of W-7 in a concentration-dependent manner. N G-Monomethyl-L-arginine (NMMA), a competitive inhibitor or nitric oxide synthase (NOS), also inhibited the NaF-induced generation of cGMP. These results suggest that NaF-induced cGMP generation occurs via a calcium/calmodulin- and NOS-dependent pathway. (b) The basal intracellular Ca2+ concentration ([Ca2+]i) was transiently greater at 1 and 3 h after pretreatment with NaF. W-7 and W-13 antagonized the increase in [Ca2+]i, whereas NMMA had little effect. This suggests that the NaF-induced change in basal [Ca2+] was mediated by a calmodulin-dependent pathway but was independent of a NOS-sensitive pathway. (c) The serotonin (5-HT)-induced intracellular mobilization of Ca2+ was reduced by pretreating the cells with NaF. The reduction in Ca2+ mobilization was antagonized by genistein, a tyrosine kinase inhibitor. W-7, W-5, and H-8 had no effect. Results suggest that NaF differentially regulated the cGMP generation. basal [Ca2+]i, and 5-HT2A receptor function in C6 glioma cells.

Animals↗

Response of patients with major depression and silent cerebral infarction to antidepressant drug therapy, with emphasis on central nervous system adverse reactions.

BACKGROUND AND PURPOSE: We previously found that silent cerebral infraction (SCI) is present in most patients older than 50 years with major depression. The present study was designed to clarify the response to antidepressant pharmacotherapy in patients with major depression associated with SCI. METHODS: Using clinical charts, we retrospectively studied patients older than 50 years who were admitted for antidepressant drug therapy. Patients with bipolar affective disorder and those with focal neurological symptoms were excluded. All patients underwent magnetic resonance imaging and were classified as SCI-negative or SCI-positive. The SCI-positive group was subclassified into those with moderate SCI (either perforating area or cortical area) (n = 15) and those with severe SCI (both perforating and cortical areas) (n = 7). Duration of treatment in hospital and the incidence of central nervous system adverse reactions to the antidepressant drugs were compared between the two groups. RESULTS: The duration of hospital treatment in patients with severe SCI was significantly longer than in those with moderate SCI (P < .01). The percentage of patients with adverse central nervous system reactions to antidepressant drugs was significantly higher in the SCI-positive group than in the SCI-negative group (P < .05). Patients with severe SCI had significantly more adverse reactions than those with moderate SCI (P < .05). CONCLUSIONS: Depressed patients with severe SCI required longer hospital treatment and had more drug-related adverse reactions of the central nervous system. These findings suggest that the depression associated with severe SCI may be resistant to treatment.

Aged↗

[Tactile extinction following the cerebral sinus thrombosis. A study using event-related potentials].

We reported a 46-year-old woman in whom cerebral sinus thrombosis manifested itself in headache and weakness while she was on an oral estrogen preparation. The neurological examinations revealed monoparesis of the right upper extremity, hyperactive right deep tendon reflex and disturbance of the joint sense, stereognostic sense, two-point discrimination and skin writing sense in the right upper extremity, in addition to tactile extinction. Brain CT showed empty triangle sign. MRI revealed infarction near the left postcentral gyrus and thrombosis of right sigmoid sinus. In the MRA study, there was low signal intensity in the posterior portion of the superior sagittal sinus and right transverse sinus. Short latency SEP in upper extremity showed that the central conduction time was normal, while the amplitude of wave components after N20 was reduced on the right side. Both palms were given bilateral or unilateral pressure stimuli. When event-related potentials (ERP) were evoked, using bilateral stimuli as a rare target, and left unilateral stimuli as a non-target, the P 300 latency was prolonged to 450 msec but was restored to normal with the improvement of tactile extinction. These results seem to suggest that the tactile extinction is ascribable to a disturbance of recognition at the higher brain function level and that ERP can be a useful objective yardstick in the evaluation of extinction phenomenon.

Event-Related Potentials, P300↗

Dissociation of cardiac hypertrophy, myosin heavy chain isoform expression, and natriuretic peptide production in DOCA-salt rats.

We examined the relationship between cardiac hypertrophy, myosin heavy chain (MHC) isoform expression, and production of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) before and after the development of DOCA-salt hypertension. DOCA-salt rats exhibited significant left ventricular hypertrophy at the prehypertensive stage (1 week of treatment), without MHC isoform switch or change in natriuretic peptide gene expression. In the hypertensive stage (5 weeks of treatment), pronounced left ventricular hypertrophy was observed, and this was characterized by an increase in beta-MHC protein, resulting in a switch from 90% alpha-MHC to 51% alpha-MHC and 49% beta-MHC. ANF and BNP mRNA levels and peptide content were significantly increased at this stage. Unexpectedly, the MHC isoform switch was evident in the non-hypertrophied right ventricle to the same degree as in the left ventricle. Natriuretic peptide production was also increased in the right ventricle at 5 weeks of treatment, but to a lesser degree than in the left ventricle. In contrast, in the hypertrophied left atrium there was no MHC isoform switch, while ANF and BNP mRNA levels were augmented. Plasma ANF was significantly increased in the prehypertensive stage; this was accompanied by a partial depletion of atrial ANF stores. Plasma BNP was increased only in the hypertensive stage, reflecting an increase in ventricular BNP synthesis and secretion. These results suggest that 1) cardiac hypertrophy, MHC isoform expression, and stimulation of natriuretic peptide production are processes that may be dissociated from each other; 2) increases in plasma ANF without a concomitant increase in plasma BNP reflect atrial hemodynamic overload, while increases in both ANF and BNP in plasma are associated with ventricular hypertrophy; and 3) there exist differences in the storage, secretion, and processing patterns of ANF and BNP in the atria.

Animals↗

Incidental Lewy body disease in a patient with REM sleep behavior disorder.

We studied an 84-year-old man with a 20-year history of nocturnal violent behavior during sleep, but no other clinically evident neuropsychiatric disorders. Polysomnographic investigations confirmed that he suffered from REM sleep behavior disorder (RBD). Histopathologic examination revealed he had Lewy body disease with a marked decrease of pigmented neurons in the locus ceruleus and substantia nigra. These histologic findings represent the first documented evidence of a loss of brainstem monoaminergic neurons in clinically idiopathic RBD and suggest that Lewy body disease might provide an explanation for idiopathic RBD in the aged.

Aged↗

[Clinical and bacteriological effects of cefetamet pivoxil against community-acquired respiratory tract infections].

We investigated clinical and bacteriological effects of cefetamet pivoxil (CEMT-PI) in community-acquired respiratory tract infections and obtained the following findings. 1. Of the 420 respiratory tract infection cases that were treated with CEMT-PI according to a same protocol at a total of 42 institutions in Tokyo, Kanagawa-ken, Saitama-ken and Chiba-ken from February to the beginning of April 1994, 359 cases in which clinical evaluations were considered possible were selected as the subjects of the clinical study. Regarding genders of patients, slightly more females (56.3%) than males were included. Diagnoses given to these patients included laryngopharygealitis (60.7%), tonsillitis (14.2%) and acute bronchitis (13.6). Outpatients accounted for 94.4% of the subjects. 2. For the bacteriological study, a written material describing the method of collecting specimens, storage and transport in detail was distributed to the above mentioned institutions. The isolation and identification of suspected causative bacteria, determination of minimum inhibitory concentrations (MIC) and investigation of beta-lactamase production were conducted all together. Suspected causative bacteria were detected from 238 (66.3%) out of the 359 cases. They included 85 strains of Haemophilus influenzae, 76 strains of Streptococcus pneumoniae, 20 strains of Streptococcus pyogenes and 17 strains of Moraxella subgenus Branhamella catarrhalis. 3. Clinical efficacy rates (the ratio of those excellent+good) among those who were treated with 1 CEMT-PI tablet (194 mg, titer) twice a day was 76.5% and among those who were given 2 tablets twice a day was 87.4%. The improvement rate of the latter was higher at a significant level of P < 0.05. 4. The clinical efficacies classified by suspected causative bacteria (single bacterium) were 93.3% against M.(B.) catarrhalis, 91.7% against beta-streptococci, 87.1% against H. influenzae and 78.4% against S. pneumoniae, etc. Though 7 (9.2%) of the 76 strains of S. pneumoniae were benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), the bacteriological efficacy was assessed either excellent or good in all of the 7 patients from whom PISP were detected. The clinical efficacy was assessed 100.0% in those from which a plural number of bacteria were detected. The 13 cases from which small numbers of Staphylococcus aureus was detected with other bacterium were also included in these cases.

Administration, Oral↗