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Biomedical subjects

M Nagai

Publications and source records attributed to M Nagai.

At least 55 records · Page 3Linked to original sources
PubMed2001

Existence of retinoic acid-receptor-independent retinoid X-receptor-dependent pathway in myeloid cell function.

We previously reported that ER-27191 (4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-pyridylmethyl)anthra[1,2-b]pyrrol-3-yl]benzoic acid) is a potent antagonist of retinoic acid receptor (RAR), and ER-35795 ((2E,4E,6E)-7-[1-(1-methylethyl)-8-chloro-1,2,3,4-tetrahydroquinolin-6-yl]-6-fluoro-3-methyl-2,4,6-nonatrienoic acid) is a novel retinoid X receptor (RXR)-specific agonist. By using these compounds, we investigated whether distinct RAR-dependent and RXR-dependent pathways operate to mediate the diverse activities of retinoids, particularly, the effects of the RXR pathway on cellular function. ER-27191 completely antagonized HL60 cell differentiation induced by all-trans-retinoic acid (atRA). However, the differentiation induced by the ER-35795 was not antagonized at all by the RAR antagonist, but was inhibited by an RXR homodimer antagonist (LGD100754, (2E,4E,6Z)-7-(3-n-propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)-3-methylocta-2,4,6-trienoic acid). Its agonistic action on RXR/RAR heterodimer, on the other hand, was neutralized by the RAR antagonist. During HL60 cell differentiation, atRA induced RARbeta mRNA, while the RXR had no effect. Interestingly, a functional RXR-pathway was also seen in lipopolysaccharide-induced inhibition of mouse splenocyte proliferation. These results strongly suggest the existence of a pharmacological RXR-dependent pathway that is activated by a ligand that can bind to RXR.

Animals↗
PubMed2001

The circadian blood pressure rhythm in non-diabetic hemodialysis patients.

This study investigates the circadian blood pressure variation of non-diabetic chronic hemodialysis (HD) patients on both HD and non-HD days as well as the factors affecting diurnal BP variation. Forty-nine HD patients aged 61.8 +/- 12.9 years who were on daytime HD for 97 +/- 68 months were studied. No significant difference was found in every daytime and nighttime BP between the first (HD) and the second (non-HD) day. However, the ratio nighttime/daytime BP was significantly higher on the second day. Each BP diurnal variability pattern was classified as either Dipper (D: the ratio nighttime/daytime mean BP 0.8-0.9), non-dipper (0.9 < ND < 1.0), or inverted dipper (ID > 1.0). More than 75% of the cases were classified as ND (26 cases) or ID (11 cases). The ultrafiltration rate in D was significantly less than that in ND and ID. The difference of plasma renin activity between pre- and post-HD (dRen) was significantly higher in ID than in D and ND. The amount of dialysis (Kt/V) was found to be significantly correlated with nighttime BP fall. Ultrafiltration, dRen and Kt/V were independent factors for the abnormal BP diurnal variability. In conclusion, the decreased nocturnal BP fall seen in non-diabetic HD patients is associated with increased extracellular fluid even in the patients without overt overhydration, whereas relatively insufficient amount of dialysis (low Kt/V) may be another possible cause. The increased dRen observed only in ID patients may reflect occult cardiovascular damage or functional disturbances in aortic and carotid baroreflexes caused by arterial structural changes.

Adult↗
PubMed2001

Identification of luminescent europium beta-diketonates using high-resolution emission spectrometry and direct-inlet electron ionization mass spectrometry.

The high-resolution emission spectra measured using a microscope Raman spectrometer and direct-inlet electron ionization mass spectrometry (DI-EIMS) were studied for the rapid analysis of a trace amount of various europium beta-diketonates in order to utilize them as fluorescent markers. Five kinds of europium beta-diketonates were distinguished from the emission spectra obtained using the Raman spectrometer. For DI-EIMS, the electron ionization mass spectra of the europium beta-diketonates showed the characteristic fragment ion peaks due to the isotope effect of 151Eu and 153Eu. The DI-EIMS was very useful for identifying the compounds compared with spectrofluorometry. The scan and selected ion-monitoring modes of DI-EIMS showed the detection limits of the samples at levels of hundreds and tens of nanograms (ng), respectively.

Europium↗
PubMed2001

Successful therapy of pure red cell aplasia secondary to plasma cell dyscrasia with bolus methylprednisolone.

A 65-year-old man, who is a Jehovah's Witness, was admitted to our hospital due to progressive anemia following a four-year history of biclonal gammopathy of no clinical significance. He was diagnosed with pure red cell aplasia (PRCA) associated with plasma cell dyscrasia. Despite a markedly decreased red blood cell count (hematocrit 5.6%), the patient refused transfusion. He was intravenously administered bolus methylprednisolone. Reticulocytosis and recovery from anemia were observed on day 7 after the start of therapy. Secondary PRCA following plasma cell dyscrasia is a rare disorder; the treatments for this rare condition are discussed.

Aged↗
PubMed2001

Lambda response by orientation of striped patterns.

A lambda response is an averaged occipital EEG potential associated with the offsets of saccadic eye movements. In the present experiment, two participants were asked to make horizontal saccades across horizontal or vertical white-black stripes. Analysis of orientations of striped patterns showed horizontal saccades across vertical stripes produced larger amplitudes of the lambda response than did horizontal saccades across horizontal stripes. Therefore, when the lambda response is used as the index of mental workload, it is necessary to take notice of the orientation of stimulus pattern.

Attention↗
PubMed2001

The pointedness effect on representational momentum.

An observer's memory for the final position of a moving object is shifted forward in the direction of that object's motion. It is called representational momentum (RM). This study addressed stimulus-specific effects on RM. In Experiment 1, participants showed larger memory shift for an object moving in its typical direction of motion than when it moved in a nontypical direction of motion. In Experiment 2, participants indicated larger memory shift for a pointed pattern moving in the direction of its point than when it moved in the opposite direction. In Experiment 3, we again examined the influences of knowledge about objects' typical motions and the pointedness of objects, because we did not control the shape (pointedness) of objects in Experiment 1. The results showed that only pointedness affected the magnitude of memory shift and that the effect was smaller than the momentum effect.

Adult↗
PubMed2001

[Statistical observation of vertigo and dizziness patients].

Subjects visiting the Department of Otolaryngology at Suita Municipal Hospital reporting vertigo or dizziness numbered 664 women and 343 men from April 1999 to December 2000. As a city hospital, we play an important role in the diagnosis and treatment of acute vertigo or dizziness. The frequency of diagnosis of these cases was divided almost equally into 5 groups: (1) benign paroxysmal positional vertigo (BPPV) 23%; (2) suspected BPPV, 18%; (3) peripheral vestibular disorders other than BPPV, 22%; (4) disorders other than peripheral origin, 18%; and (5) undiagnosed, 19%. Based on our results, BPPV, other peripheral vestibular disorders, and disorders of other origins should be differentiated from the first screening. BPPV was most frequent and diagnosed by typical positioning nystagmus. Many other peripheral vestibular disorders were accompanied by nystagmus. It is also important to differentiate serious illnesses such as cerebrovascular disease (7%), space-occupying lesions in the posterior fossa (1.2%), and cardio-circulatory disease (3.6%).

Adult↗
PubMed2001

[Clinical features of benign paroxysmal positional vertigo].

Our understanding of the pathomechanism of benign paroxysmal positional vertigo (BPPV) has improved dramatically. A type of BPPV featuring mixed torsional and vertical nystagmus induced by the Dix-Hallpike maneuver involves the posterior semicircular canal (P-BPPV). The other type of BPPV featuring horizontal nystagmus induced by spine-to-lateral head positioning involves the horizontal canal BPPV (H-BPPV). In complaints of vertigo or dizziness, 619 patients visited our department last year. Of these, 142 (23%) was had positional nystagmus consistent with a diagnosis of BPPV, 118 (19%) had no nystagmus but were suspected of BPPV due to vertigo episodes. BPPV was the most frequent diagnosis. H-BPPV was not rare, but accounted for 30% of BPPV. Of H-BPPV, 73% featured direction changing geotropic nystagmus, and 27% direction changing apogeotropic nystagmus. H-BPPV resolved faster than P-BPPV. Most cases caused by head trauma were P-BPPV. Transition between P- and H-BPPV was found in 6 cases. Women outnumbered men by about 3 to 2 in both P- and H-BPPV. Peak incidence was found in the those in their 60s and 70s, suggesting that the etiologies of both types of BPPV are essentially the same.

Adult↗
PubMed2001

[A family of early childhood-onset Charcot-Marie-Tooth disease type 2].

We reported a man and his son with Charcot-Marie-Tooth disease (CMT) type 2. Their age at onset was about 5 years. Their clinical examinations revealed muscle atrophy and weakness of both distal lower limbs, foot-drop, a reduction of the reflex in both Achilles tendons and sensory impairment of the glove and stocking type. Nerve conduction studies revealed remarkably low amplitude of compound muscle action potential compared to conduction velocity. The nerve biopsy of their sural nerves revealed loss of large myelinated fiber. We presumed that the clinical features of their disease were compatible with CMT2A or 2B. DNA analysis of our family members performed with microsatellite markers linked to the candidate regions of CMT2A and 2B, did not show apparent positive results. We speculate that this family was a novel gene locus of CMT type 2.

Adult↗
PubMed2001

[Adrenal gland lymphoma accompanied by renal cell carcinoma].

A 76-year-old man was admitted with right hypochondralgia. Computed tomography revealed tumors measuring 90 mm and 20 mm in the right adrenal gland and kidney, respectively. Under a diagnosis of renal and adrenal cancer, the patient underwent nephro-adrenectomy, which revealed renal cell carcinoma in the kidney and non-Hodgkin's B-cell lymphoma of the diffuse large cell type in the adrenal grand. The patient has been disease-free for ten months after the operation. To our knowledge, this is the first report of coexisting renal cell carcinoma and adrenal lymphoma. The relationship between these two disorders in our patient is discussed.

Adrenal Gland Neoplasms↗
PubMed2000

Increased activated human T cell lymphotropic virus type I (HTLV-I) Tax11-19-specific memory and effector CD8+ cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: correlation with HTLV-I provirus load.

To discern the T cell subtype associated with T cell differentiation, the expression of CD45RA and CD27 was measured from total CD8(high) cells and from human T cell lymphotropic virus type I (HTLV-I) Tax11-19 peptide-specific CD8(+) cells in peripheral blood lymphocytes of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Phenotypically defined memory and/or effector cells (CD45RA(-)CD27(+), CD45RA(+)CD27(-), and CD45RA(-)CD27(-)) were increased in HAM/TSP CD8(+) cells, compared with those of HTLV-I-seronegative healthy control subjects. The percentage of human leukocyte antigen (HLA)-DR-positive cells was also increased in CD8(+) cells of HAM/TSP, compared with those in HLA-DR(+)CD8(+) cells of healthy control subjects. HTLV-I provirus load correlated with the frequency of Tax11-19-specific CD8(+) cells. The high frequency of memory and/or effector type HTLV-I Tax11-19-specific CD8(+) cells suggests that continuous restimulation driven by HTLV-I antigens in vivo may be associated with the pathogenesis of HAM/TSP.

Adult↗
PubMed2000

Efficacy of chemically cross-linked antigens for acellular pertussis vaccine.

The efficacy of chemically cross-linked antigens for acellular pertussis vaccine was investigated by a murine respiratory infection model. Filamentous hemagglutinin (FHA), pertussis toxin (PT) and pertactin, prepared from a supernatant fluid of Bordetella pertussis culture or the bacterial cells, were chemically cross-linked by the addition of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysulfosuccinimide (NHSS). The biological activities of FHA and PT were inactivated by the cross-linking reaction. The cross-linked antigens induced potent protective immunity against B. pertussis more than the vaccine prepared by formalin treatment (0.2 M). These data suggest a possibility that the vaccine prepared by using EDC and NHSS is more effective than the formalin-treated vaccine.

Adhesins, Bacterial↗
PubMed2000

Increased HTLV type 1 tax specific CD8+ cells in HTLV type 1-asociated myelopathy/tropical spastic paraparesis: correlation with HTLV type 1 proviral load.

Less than 1% of individuals infected with the human T lymphotropic virus type 1 (HTLV-1) develop an inflammatory neurological disorder, termed HTLV-1-associated myelopathy/tropical spastic (HAM/TSP), while the vast majority of those infected remain asymptomatic HTLV-1 carriers (ACs). The fundamental viroimmunological differences between these groups are not well understood. To address this issue, we have investigated HTLV-1-specific T cell responses and measured the proviral load in these groups. Frequencies of HTLV-1-specific CD8(+) cells were demonstrated to be significantly higher in HAM/TSP patients than in ACs by using intracellular cytokine staining and soluble divalent HLA-A2/Ig fusion protein loaded with HTLV-1 Tax 11-19 peptide. It is consistent with the observed increase in HTLV-1-specific cytotoxic T lymphocytes in HAM/TSP patients. These CD8(+) cells produced interferon (IFN)-gamma in recognition of HTLV-1 antigens bound to HLAs on the infected CD4(+) cells. Using phenotypic markers indicative for T cell differentiation, memory and/or effector HTLV-1 Tax-specific CD8(+) cells were found to be increased in HLA-A2 HAM/TSP patients. HTLV-1 proviral load was elevated in HAM/TSP patients when compared to ACs. In addition, the proviral load in HAM/TSP patients correlated with the frequency of HTLV-1-specific IFN-gamma(+)CD8(+) cells or Tax-HLA-A2/Ig(+)CD8(+) cells, especially with the effector cells. In contrast, the proviral load inversely correlated with memory cells. These results suggest that HTLV-1 antigens may continuously stimulate HTLV-1-specific CD8(+) cells and differentiate them from memory cells into effector cells in vivo. These differentiated HTLV-1-specific CD8(+) cells may play a role in the pathogenesis of HAM/TSP.

CD8-Positive T-Lymphocytes↗
PubMed2000

Antitumor-promoting effects of cyclic diarylheptanoids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.

Eleven cyclic diarylheptanoids were screened as potential antitumor promoters by examining the ability of the compounds to inhibit Epstein-Barr virus early antigen activation (induced by 12-O-tetradecanoylphorbol-13-acetate) in Raji cells. 13-Oxomyricanol and myricanone showed the highest activity and also exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These data suggest that certain diarylheptanoids might be valuable antitumor promoters and/or chemopreventors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Heme structure of hemoglobin M Iwate [alpha 87(F8)His-->Tyr]: a UV and visible resonance Raman study.

Heme structures of a natural mutant hemoglobin (Hb), Hb M Iwate [alpha87(F8)His-->Tyr], and protonation of its F8-Tyr were examined with the 244-nm excited UV resonance Raman (UVRR) and the 406.7- and 441.6-nm excited visible resonance Raman (RR) spectroscopy. It was clarified from the UVRR bands at 1605 and 1166 cm(-)(1) characteristic of tyrosinate that the tyrosine (F8) of the abnormal subunit in Hb M Iwate adopts a deprotonated form. UV Raman bands of other Tyr residues indicated that the protein takes the T-quaternary structure even in the met form. Although both hemes of alpha and beta subunits in metHb A take a six-coordinate (6c) high-spin structure, the 406.7-nm excited RR spectrum of metHb M Iwate indicated that the abnormal alpha subunit adopts a 5c high-spin structure. The present results and our previous observation of the nu(Fe)(-)(O(tyrosine)) Raman band [Nagai et al. (1989) Biochemistry 28, 2418-2422] have proved that F8-tyrosinate is covalently bound to Fe(III) heme in the alpha subunit of Hb M Iwate. As a result, peripheral groups of porphyrin ring, especially the vinyl and the propionate side chains, were so strongly influenced that the RR spectrum in the low-frequency region excited at 406.7 nm is distinctly changed from the normal pattern. When Hb M Iwate was fully reduced, the characteristic UVRR bands of tyrosinate disappeared and the Raman bands of tyrosine at 1620 (Y8a), 1207 (Y7a), and 1177 cm(-)(1) (Y9a) increased in intensity. Coordination of distal His(E7) to the Fe(II) heme in the reduced alpha subunit of Hb M Iwate was proved by the observation of the nu(Fe)(-)(His) RR band in the 441.6-nm excited RR spectrum at the same frequency as that of its isolated alpha chain. The effects of the distal-His coordination on the heme appeared as a distortion of the peripheral groups of heme. A possible mechanism for the formation of a Fe(III)-tyrosinate bond in Hb M Iwate is discussed.

Amino Acid Substitution↗