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Biomedical subjects

M Nagai

Publications and source records attributed to M Nagai.

At least 73 records · Page 4Linked to original sources

Pleasant odors attenuate the blood pressure increase during rhythmic handgrip in humans.

We have investigated the effects of inhaling odors of preference on physiological responses to physical exercise in college students. Rhythmic handgrip, maintaining a mercurial pressure by repetitive compression, increased blood pressure. In the participants exercised with inhaling odors of their choice, such as rose, jasmine and lavender, the increase in diastolic blood pressure during exercise was reduced by 24%. In contrast, the blood pressure increase during static handgrip, maintaining the power 30-40% of maximum, was not affected by the existence of favorite odors. Since the blood pressure increase during static handgrip is a lower brainstem reflex, the present result shows that the inhalation of favorite odors suppresses the muscle sympathetic vasoconstrictor activity and attenuates the blood pressure increase by affecting the central nervous system higher than the midbrain.

Adolescent↗

Familial spinal arachnoiditis with secondary syringomyelia: clinical studies and MRI findings.

We report the clinical and MRI findings of two patients with familial spinal arachnoiditis. Although their initial symptoms were various, they both showed spastic paraparesis and sensory disturbance below the thoracic level. Cytokines and WBC in the CSF were studied, but they were not elevated at all. The spinal magnetic resonance images of each showed extensive arachnoiditis and a cystic structure. The other impressive features included: (i) an enhancement within the thickened arachnoid and an adhesion between the spinal cord and the dura mater, (ii) deformation of the thoracic cord where the arachnoid adhered, and (iii) secondary syrinx formation. Laminectomy may have an adverse outcome for such patients.

Arachnoiditis↗

Discovery of novel and potent retinoic acid receptor alpha agonists: syntheses and evaluation of benzofuranyl-pyrrole and benzothiophenyl-pyrrole derivatives.

In the course of our studies on retinoic acid receptor (RAR) agonists, we have designed and synthesized a series of benzofuran and benzothiophene derivatives. Some of these compounds (1a,b,e,f,j) markedly inhibited LPS-induced B-lymphocyte proliferation and exerted RARalpha selectivity. One of them, 4-[5-(4,7-dimethylbenzofuran-2-yl)pyrrol-2-yl]benzoic acid (1b), when orally administered significantly inhibited mouse antibody production and delayed type hypersensitivity (DTH) responses from a dose of 0.1 mg/kg.

Administration, Oral↗

Novel retinoic acid receptor alpha agonists: syntheses and evaluation of pyrazole derivatives.

We have designed and synthesized a series of pyrazole derivatives as candidate retinoic acid receptor (RAR) agonists. One of them, 4-[5-(1, 5-diisopropyl-1H-3-pyrazolyl)-1H-2-pyrrolyl]benzoic acid (11b), which possesses a 2,5-disubstituted pyrrole moiety, showed selective transactivation activity for the RAR alpha receptor, and had highly potent cell-differentiating activity on HL-60 cells.

Binding, Competitive↗

Cancer cells responsible for humoral hypercalcemia express mRNA encoding a secreted form of ODF/TRANCE that induces osteoclast formation.

A novel cDNA encoding a secreted form of osteoclast differentiation factor/tumor necrosis factor-related activation-induced cytokine (sODF/TRANCE, GenBank Accession No. AB037599) was sequenced from 5' RACE cDNA clones of squamous cell carcinoma cell lines, SCC-4 and T3M-1 Cl.2, of which parental malignant tissues had caused severe humoral hypercalcemia. The sODF/TRANCE cDNA was composed of unknown 5' end sequence followed by the 100% identical sequence of the ODF/TRANCE extracellular domain-coding region. The longest open reading frame (ORF) of the novel cDNA completely matched the 3' end of the ORF of the ODF/TRANCE cDNA encoding C-terminal amino acid residues (74-318) in the extracellular region. The corresponding protein that reacted with the antibody specific for the extracellular domain of ODF/TRANCE was detected in the culture media conditioned by the cancer cells. Furthermore, human promyeloblastic leukemia cells, HL60, differentiated into osteoclast-like cells (OCLs) when cultured in the media conditioned by SCC-4 and T3M-1 Cl. 2 cells. The differentiation of HL60 cells into OCLs was inhibited by the anti-ODF/TRANCE antibody. These results strongly suggest that sODF/TRANCE plays an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.

Amino Acid Sequence↗

Syntheses and structure-activity relationships of 5,6,7, 8-tetrahydro-5,5,8,8-tetramethyl-2-quinoxaline derivatives with retinoic acid receptor alpha agonistic activity.

In the course of our studies on retinoic acid receptor (RAR) agonists, we have designed and synthesized a series of quinoxaline derivatives. One of them, 4-[5-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethyl-2-quinoxalinyl)-1H-2-pyrrolyl]benzoic acid (3a), which possesses a 2,5-disubstituted pyrrole moiety, showed selectivity for the RARalpha receptor and exerted highly potent cell-differentiating activity on HL-60 cells.

Benzoates↗

Contribution of alpha140Tyr and beta37Trp to the near-UV CD spectra on quaternary structure transition of human hemoglobin A.

The CD band of human adult hemoglobin (Hb A) at 280 approximately 290 nm shows a pronounced change from a small positive band to a definite negative band on the oxy (R) to deoxy (T) structural transition. This change has been suggested to be due to environmental alteration of Tyrs (alpha42, alpha140, and beta145) or beta37 Trp residues located at the alpha1beta2 subunit interface by deoxygenation. In order to evaluate contributions of alpha140Tyr and beta37Trp to this change of CD band, we compared the CD spectra of two mutant Hbs, Hb Rouen (alpha140Tyr-->His) and Hb Hirose (beta37Trp-->Ser) with those of Hb A. Both mutant Hbs gave a distinct, but smaller negative CD band at 287nm in the deoxy form than that of deoxyHb A. Contributions of alpha140Tyr and beta37Trp to the negative band at the 280 approximately 290 nm region were estimated from difference spectra to be 30% and 26%, respectively. These results indicate that the other aromatic amino acid residues, alpha42Tyr and beta145Tyr, at the alpha1beta2 interface, are also responsible for the change of the CD band upon the R-->T transition of Hb A.

Adult↗

Interactions of phosphatidylinositol 3-kinase Src homology 3 domain with its ligand peptide studied by absorption, circular dichroism, and UV resonance raman spectroscopies.

Absorption, circular dichroism (CD), and UV resonance Raman (UVRR) spectroscopies were applied to selectively examine the environmental and structural changes of Trp and Tyr residues in the phosphatidylinositol 3-kinase (PI3K) SH3 domain induced by ligand association. Comparison of the spectra of PI3K SH3 in the presence or absence of its ligand peptide RLP1 (RKLPPRPSK) indicated that RLP1 binding changed the environment of Trp55 of the SH3 to be more hydrophilic and its H bonding weaker and that of Tyr residues to be more hydrophobic. The D21N mutant (Asp21 --> Asn) of the SH3 yielded a UV CD distinct from that of the wild type, and its spectral changes induced by RLP1 binding were smaller and different from those of the wild type in absorption, CD, and UVRR spectra, suggesting that the mutation of conserved Asp21 affected the conformation of the ligand binding cleft and thus might lead to the decrease in the ligand affinity. These data provide direct evidence for the occurrence of environmental and structural changes of PI3K SH3 by the association of a ligand and the D21N mutation.

Absorption↗

Changes of tyrosine and tryptophan residues in human hemoglobin by oxygen binding: near- and far-UV circular dichroism of isolated chains and recombined hemoglobin.

In order to assign the circular dichroism (CD) spectral change in the region between 280 and 300 nm of human adult hemoglobin (Hb A) upon the quaternary structure transition induced by oxygen binding, the near- and far-UV CD spectra of the isolated chains and the recombined hemoglobin were examined. Deoxygenation made the negative CD band at 290 nm of oxy-alpha chain deeper. On the other hand, positive CD bands of oxy-beta chain at the 280 to approximately 300 nm became negative upon deoxygenation. These changes were interpreted as being due to environmental alterations of tyrosine (Tyr) and/or tryptophan (Trp) perturbed by tertiary structural changes from the oxy to deoxy form in isolated chains, referring to the CD spectra of model compounds. From the difference between CD bands of the arithmetic mean of deoxy isolated chains and the CD band of deoxyHb tetramer, the contribution of tertiary structural change to the negative CD band of deoxyHb A at 287 nm was estimated to be 50%. This finding has revealed that the net contribution of quaternary structure transition to the negative band is 50%. In far-UV CD spectra, the environmental changes of aromatic residues upon the quaternary structure transition were also detected as a negative band at 225 nm.

Amino Acid Substitution↗

The perfusion defect seen with SPECT in West syndrome is not correlated with seizure prognosis or developmental outcome.

We used interictal single photon emission computed tomography (SPECT) on 40 patients with West syndrome to determine whether cortical perfusion abnormalities are closely related to the development of West syndrome and whether they are correlated with the long-term seizure prognosis or the developmental outcome. Localized cortical perfusion abnormalities were seen in 24 patients (60%), while 15 patients (38%) were classified as normal. The remaining patient showed hyperperfusion of the basal ganglia bilaterally. Of 24 patients with localized perfusion abnormalities, unifocal cortical hypoperfusion was present in 11, multifocal hypoperfusion in 10, multiple cortical hypo- and hyperperfusion in one, hyperperfusion of the bilateral frontal cortices and brain stem in one, and focal hyperperfusion in the residual frontal cortex in one. For statistical analysis, we focused on 26 patients (cryptogenic; 10, symptomatic; 16), who were followed for more than 2 years after the onset of tonic spasms (mean 5.0 years). The results showed that focal cortical perfusion abnormalities were not correlated with the long-term seizure prognosis, the developmental outcome, or the response to ACTH therapy. In agreement with previous reports, the results of interictal SPECT suggested that focal cortical lesions play an important role in the development of West syndrome. However, statistical analysis showed that the existence of cortical dysfunction as defined by SPECT did not predict the seizure prognosis or the developmental outcome.

Cerebral Cortex↗

Differential responses of Bcl-2 family genes to etoposide in chronic myeloid leukemia K562 cells.

Etoposide is a potent anticancer agent that is used to treat various tumors. We have investigated the dose-dependent effect of etoposide on apoptosis using chronic myeloid leukemia K562 cells treated with low (5 microM) or high (100 microM) concentrations of the drug. At a low concentration, etoposide induced little apoptosis at 24 h, while about 20% of the cells showed apoptosis morphologically at a high concentration. Processing of caspase-3 was slightly detected from 12 h and became obvious at 24 h with 100 microM etoposide. Caspase-3-like protease activity was detected at 24 h with a high concentration. Moreover, these changes were accompanied by cleavage of poly ADP ribose polymerase (PARP). Changes of the mRNA levels of most apoptosis-regulating genes were not prominent at both concentrations, except for the rapid induction of c-IAP-2/HIAP-1 and the down-regulation of Bcl-X(L) by 100 microM etoposide. The downregulation of Bcl-X(L) protein occurred from 6 h, while Bax protein conversely showed a slight increase from 6 h. Taken together, the present findings show that the dose-dependent apoptotic effect of etoposide is based on a change in the balance between Bcl-X(L) and Bax, which precedes the activation of caspase-3.

Antineoplastic Agents, Phytogenic↗

Dietary restriction initiated late in life can reduce mitochondrial protein carbonyls in rat livers: western blot studies.

Life long dietary restriction has a variety of beneficial effects such as retarding the age-related decline of physiological functions as well as the onset of diseases, thus prolonging the life span of experimental animals. In the present work we investigated the effect of DR initiated late in life on rats regarding oxidative modifications of liver mitochondrial proteins in terms of generation of carbonyl moieties by western blot using antibodies against dinitrophenylhydrazones after the reaction of the proteins with dinitrophenylhydrazine. Protein carbonyls in mitochondria of 30-month-old animals increased by about 55% as compared with their 10-month-old counterparts. Every-other-day feeding initiated at the age of 26.5 months and continued for 3.5 months resulted in the decrease of the carbonyls to the level of the ad libitum fed young animals. Our findings suggest that DR initiated late in life can have a beneficial effect by reducing the accumulated oxidative damage in mitochondrial proteins.

Aging↗

Ion chromatographic analysis of hydronium ion using ODS modified with dodecylsulfate as the stationary phase.

The hydronium ion (H3O+), the most essential species to every field of chemistry, was successfully separated from other cations. This major goal was achieved by a HPLC approach in which a reversed-phase ODS which had been initially modified with dodecylsulfate was used as the stationary phase and an aqueous KNO3 solution was used as the mobile phase. Of all tested monovalent cations (analyte ions), the hydronium ion (H3O+) showed the highest affinity towards the stationary phase, followed by NH4+, Na+, and then Li+. The hydronium ion, after the separation, was directly detected using conductivity and the detection signal (conductivity) was in linear proportion (linear range 7.8 x 10(-4)-0.45 M; injection volume, 100 microL) to the concentration of the acid species of the tested sample. This proposed HPLC method was applicable to separate/detect H3O+ from both strong and weak acidic samples.

Journal Article↗

CD138-positive and Kaposi's sarcoma-associated herpesvirus (KSHV)-negative B-cell lymphoma with serosal spreading of the body cavity and lymphadenopathy: an autopsy case.

CD138-positive and Kaposi's sarcoma-associated herpes virus (KSHV)-negative B cell lymphoma with serosal spreading of the body cavity and lymphadenopathy is presented. Our lymphoma cells showed pleomorphic morphology and a clonal immunoglobulin gene rearrangement. Immunophenotypically, they lacked B- and T-cell-associated antigens but expressed strong membranous CD138 antigen along the serosa. Although our case was not conventional primary effusion lymphoma (PEL) because of the absence of KSHV and the presence of lymphadenopathy, its unique phenotype and serosal spreading were consistent with those of PEL. Our case suggests that, irrespective of KSHV infection, some pleomorphic B cell lymphomas with membranous CD138 expression show a peculiar serosal spreading.

Ascites↗

Anatomical segmentectomy of the head of the pancreas along the embryological fusion plane: a feasible procedure?

BACKGROUND: Less extensive resection of the head of the pancreas has been the procedure of choice recently for low-grade malignant neoplasms. The anatomical detail of the head of the pancreas is currently insufficient for segmental resection along the embryological fusion plane. METHODS: The anatomy of the head of the pancreas was analyzed in 31 consecutive autopsy specimens. An anterior (n = 10) or posterior (n = 10) segmentectomy of the head of each pancreas was performed along the macroscopically found fusion plane. The pancreatic arteries, the portal vein, the bile duct, and the pancreatic duct were visualized by injecting 3 silicon dyes of different colors. Another 11 specimens were examined by pancreatography before and after anterior (n = 5) or posterior (n = 6) segmentectomy. Eight of these 11 specimens were stained immunohistochemically to reveal the distribution of pancreatic polypeptide cells after segmentectomy. RESULTS: The cleavage between the anterior and posterior segments was discovered at the anterior inferior edge or at the posterior superior edge of the head of the pancreas. Anterior segmentectomy was accomplished while preserving the anterior and posterior pancreaticoduodenal arcades and the lower bile duct in the posterior segment. Posterior segmentectomy involved the removal of the lower bile duct and the posterior pancreaticoduodenal arcades. Pancreatography after segmentectomy showed the division of the ducts of Wirsung and Santorini with the peripheral branches. The immunohistochemical boundary of pancreatic polypeptide cells coincided with the surgical plane. These results showed the anterior and posterior segments were originated from the embryologically dorsal and ventral primordia, respectively. CONCLUSIONS: The current anterior or posterior segmentectomy of the head of the pancreas corresponded to the resection of the embryologically dorsal or ventral primordium, respectively. Anterior segmentectomy of the head of the pancreas might be a clinically applicable procedure; however, posterior segmentectomy involving the resection of the lower bile duct may be impractical.

Adult↗

Detection of epidemics in their early stage through infectious disease surveillance.

BACKGROUND: Surveillance of infectious diseases is done in many countries. The aims of such surveillance include the detection of epidemics. In the present study, the possibility of detecting an epidemic in its early stage using a simple method was evaluated for 16 infectious diseases. METHODS: We used as an index the number of cases per week per sentinel medical institution in the area covered by a health centre in infectious disease surveillance in Japan in 1993-1997. Periods of epidemics in health centre areas were determined according to the reported indices. The simple method used for detecting the early stage of an epidemic is that if the index exceeds a critical value, then an epidemic will begin in the following 4 weeks. The sensitivity, specificity and positive predictive value for this epidemic warning were evaluated for given critical values. RESULTS: When the specificity of the epidemic warning was more than 95%, the sensitivity was more than 60% in ten diseases, and more than 80% in four diseases (influenza-like illness, rubella, hand-foot-and-mouth disease, and herpangina). The positive predictive value was between 15.6% and 31.4% in these ten diseases. CONCLUSION: The early stage of epidemics of some infectious diseases might be detectable using this simple method.

Communicable Diseases↗

Oleanane acid from Myrica cerifera.

From the twigs of Myrica cerifera L. (Myricaceae), a new oleanane triterpenic acid named myrica acid was isolated along with myricalactone and several other known constituents. The structure of the acid was determined as 3beta-hydroxy-1-oxoolean-11,13(18)-dien-28-oic acid on the basis of chemical and spectral evidence.

Molecular Structure↗