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Biomedical subjects

M Nagai

Publications and source records attributed to M Nagai.

At least 217 records · Page 12Linked to original sources

Dissecting aneurysm of the anterior cerebral artery causing hemorrhagic infarction.

BACKGROUND: Dissecting aneurysms of the cerebral arteries are infrequent, and they occur preferentially in the middle cerebral, internal carotid, and vertebrobasilar arteries. The anterior cerebral artery (ACA) is usually involved in association with dissection in other locations, but a lesion confined to the ACA is an extremely rare event. No previous reports have well documented the clinical and pathological features of the ACA dissection. Moreover, surgical management for this lesion has not been reported. CASE REPORT: A case of dissecting aneurysm confined to the ACA causing hemorrhagic infarction is presented. To prevent subsequent rupture, we employed a trapping procedure 12 days after the onset. A dark purplish discoloration of the right A2 portion was encountered, with an intact anterior communicating complex. The involved vessel was partly sectioned for further pathological examination. RESULTS: Pathologically, subintimal clots dissected the vascular lumen in the inner layer of the media. Other abnormalities such as deficiency of the internal elastic lamina and medial defects were not found. The postoperative clinical course was not eventful. CONCLUSIONS: This is the first case to document an ACA dissecting aneurysm treated by a direct surgical approach. Spontaneous resolution is not infrequent in cerebral dissection, but subsequent rupture has commonly resulted in poor outcome. Surgical management is thought to be the most effective method to prevent further hemorrhagic event, even for an ACA dissection. Revascularization distal to the compromised artery should be considered whenever necessary.

Cerebral Angiography↗

Prostaglandin E2 increases the calcium concentration in rat brown adipocytes and their consumption of oxygen.

Effects of prostaglandin E2 (PGE2) were examined on the oxygen consumption and intracellular calcium concentration of rat brown adipose tissue (BAT). PGE2 0.1 nM-1 microM increased oxygen consumption of the tissue blocks of BAT, with a maximum 2-13 min after PGE2 administration. PGE2 was most effective at 1 and 10 nM, and the oxygen consumption was elevated for over 40 min. Pretreatment of BAT with indomethacin, a prostaglandin synthesis inhibitor, did not affect the increase in oxygen consumption induced by noradrenaline. PGE2 at 1-10 nM gradually increased the intracellular calcium concentration of freshly dispersed single brown adipocytes by 3-4 times in 30 min. PGF2 also increased the intracellular calcium concentration of brown adipocytes in calcium-free medium. These results raise the possibility that PGE2 and noradrenaline affect heat genesis and metabolism of BAT independently.

Adipose Tissue, Brown↗

Infrequent microsatellite instability during the evolution of myelodysplastic syndrome to acute myelocytic leukemia.

Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed throughout the genome. Instability of these repeat sequences at multiple gentic loci may result from mismatch repair errors and occur in hereditary nonpolyposis colorectal cancer and several other sporadic cancers, including chronic myelocytic leukemia as it progresses to blastic crisis. We investigated whether genetic instability occurred as myelodysplasia progressed to acute myelocytic leukemia. To this end, we studied microsatellite instability in 20 patients with myelodysplastic syndrome (MDS). These included five patients with refractory anemia (RA), three with refractory anemia with ringed sideroblast (RARS), nine with refractory anemia with excess blasts (RAEB) and three with chronic myelomonocytic leukemia (CMML). All of these patients transformed to acute myelocytic leukemia (AML) of various subtypes: three patients with M1, 11 with M2 and six patients with M4 (according to FAB classification). The DNA from both the MDS and AML phases of their disease was analyzed at 16 loci, and only four microsatellite instabilities were found in the 240 paired samples (1.6%) analyzed. These results indicate that mismatch repair errors such as microsatellite instability are not important in the evolution of MDS to AML.

Adult↗

Characterization of a unique T-cell clone established from a patient with HAM/TSP which recognized HTLV-I-infected T-cell antigens as well as spinal cord tissue antigens.

Five T-cell clones reactive to autologous HTLV-I-infected T-cells (KODA-TV) were established from peripheral blood lymphocytes of a HAM/TSP patient (KODA) by the limiting dilution method. All the clones showed CD3+, CD4+ and CD25+ surface markers and expressed alpha beta+ T-cell receptors to recognize KODA-TV antigens. One of the five T-cell clones (KODA-408) was infected with HTLV-I but the remaining four clones (KODA-400, 404, 405 and 409) were free of HTLV-I infection. KODA-408 recognized both KODA-TV and spinal cord antigens, the latter being extracted from autopsy tissues of a HTLV-I seronegative donor. KODA-408 did not recognize either alloantigens of peripheral blood mononuclear cells extracted from unrelated HTLV-I seronegative donors or purified human myelin basic protein. KODA-408 T-cell clone produced a considerable amount of TNF-alpha, IFN-gamma, and IL-6. The CDR3 motif of KODA-408 T-cell receptor showed a unique sequence CASSAGQS of v beta 8-D beta-J beta 1.5. These results indicated that HAM/TSP CD4+ T-cells were polyclonally activated by HTLV-I infection and antigenic stimulation. The T-cell repertoire shaped by HTLV-I infection included T-cells which recognized HTLV-I-infected T-cell antigens as well as spinal cord antigen in particular.

Aged↗

Herbimycin A down-regulates messages of cyclin D1 and c-myc during erythroid differentiation of K562 cells.

The ansamycin antibiotic, herbimycin A, is a potent tyrosine kinase inhibitor, and induces the erythroid differentiation of bcr-abl-possessing K562 cells. The growth of K562 cells was cytostatically reduced to less than 50% of the control level at 48 h by 0.5 microgram/ml of herbimycin A treatment. A total of 12% and 53% of the treated cells were benzidine-positive at 24 h and 48 h, respectively. The percentage of cells in the S phase decreased rapidly from 60% to 15% after 12 h of treatment. The reduction of S phase cells persisted until 24 h, whereas the G1 population conversely increased. Then underphosphorylated retinoblastoma gene product increased from 6 h to 24 h, but returned to baseline at 48 h. Most cell cycle controlling genes were unchanged by herbimycin A treatment. However, both cyclin D1 and c-myc were prominently down-regulated in the early phase of treatment, corresponding to the decline of the S phase population. Cyclin D1 was initially down-regulated to an undetectable level at 6 h, although its expression recovered gradually from 12 h and returned to baseline at 24 h. c-myc was also down-regulated from 1 h to 6 h. These data suggest that signals originating from bcr-abl kinase are at least partly transduced through both c-myc and cyclin D1, and that herbimycin A-induced erythroid differentiation occurs during or after the cessation of growth due to interference with these signals.

Antibiotics, Antineoplastic↗

Granulocyte-colony stimulating factor concentrations in a patient with plasma cell dyscrasia and clinical features of chronic neutrophilic leukaemia.

In order to study the pathogenesis of plasma cell dyscrasias with associated clinical features of chronic neutrophilic leukaemia, the concentration of granulocyte-colony stimulating factor (G-CSF) was measured in a patient, a 73 year old man, who underwent steroid pulse therapy. High G-CSF concentrations and leucocyte counts prior to treatment declined rapidly on administration of dexamethazone, but rose subsequently. G-CSF was not detected in primary cultures of bone marrow cells, but large amounts of interleukin-6 were found in the culture supernatant. These observations suggest that the neutrophilia observed in the patient represented a reactive response to G-CSF secreted from abnormal plasma cells or stromal cells rather than the existence of a genuine myeloproliferative disorder.

Aged↗

Production of antibody against calmodulin which is a protein with poor antigenicity.

Calmodulin (CaM), a Ca(2+)-binding protein, is a multifunctional modulator mediating the calcium regulation of a large number of intracellular enzyme systems. Because of its highly conserved structure, it has been difficult to produce anti-CaM antibody. We describe here a simplified method for production of this antibody. BALB/c mice were immunized with a polymerized CaM, and the serum was prepared and tested for the presence of anti-CaM antibody by immunoblot analysis. The serum obtained from the immunized mice was shown to contain anti-CaM antibody. Immunoblot analysis proved that a 500-fold diluted serum was able to recognize both types of CaM with a polymerized form and monomer form. The method developed in this study may be applicable to a wide range of proteins for enhancement of antigenicity.

Animals↗

Failure of smooth muscle cells treated with collagenase to respond to Bordetella heat-labile toxin.

HLT, bordetella heat-labile toxin, caused a release of radioactivity from cultured smooth muscle cells (SMC) previously labeled with [14C]arachidonic acid, and from membrane preparations from the labeled SMC. HLT, however, failed to induce release from primary SMC prepared by treatment with an enzyme solution containing collagenase and elastase. When cultured SMC were treated with the enzyme solution, their susceptibility to HLT was reduced more significantly than that of untreated cells. SMC also lost their susceptibility, after treatment with collagenase alone, but not with elastase, in a dose-dependent manner. These data suggest that collagen on the SMC surface might play an important role in HLT activity.

Animals↗

Vasodilator effects of des(alpha-carboxy-3,4-dihydroxyphenethyl)lithospermic acid (8-epiblechnic acid), a derivative of lithospermic acids in salviae miltiorrhizae radix.

A potent vasodilator substance (compound III), [alpha]D +141 degrees, was isolated from salviae miltiorrhizae radix (dan-shen). This substance was determined to be des(alpha-carboxy-3,4-dihydroxyphenethyl)lithospermic acid on the basis of spectrometric and chemical evidence, and was identified with an authentic sample of 8-epiblechnic acid. However, comp. III seemed to be formed from lithospermic acid (LSA) and LSA-B during a chemical procedure to separate active ingredients. It caused a sustained, slowly developing relaxation of rat aortic strips precontracted with norepinephrine (NE) in preparations with or without endothelium. The NE-induced concentration-dependent contraction of aortic strips was significantly attenuated by pretreatment with comp. III. Concentration-response curves for Ca(2+)-induced contracture of depolarized aortic strips with isotonic high K+ (60 nM) were not affected by comp. III. Ca(2+)-induced contraction of aortic strips, preincubated with 10(-6) M NE in the presence of 10(-6) M nicardipine and 0.01 mM EGTA in Ca(2+)-free solution, was slightly inhibited by comp. III. Pretreatment of aortic strips with comp. III slightly inhibited the phorbol ester (PMA)-induced contraction. These results suggest that comp. III inhibits NE-induced contraction of the aortic strips through reduction in Ca2+ mobilization. Since comp. III inhibits NE-induced sustained contraction, this agent may be useful in the treatment of hypertension.

Animals↗

[Chemical constituents of original plants of Cimicifugae rhizoma in Chinese medicine].

Cimicifugae Rhizoma have been used as an anti-inflammatory, analgesic and antipyretic remedy in the traditional Chinese medicines. Many 9,19-cyclolanostane glycosides have been isolated from Cimicifuga and related genera. Two biogenetically key compounds, acetylshengmanol xyloside and cimicifugoside H-1, were isolated and their chemical structures were elucidated by our group. The former compound seems to be the parent component of the other glycosides such as cimigenol xyloside from C. dahurica, C. iaponica and C. acerina. The latter glycoside, cimicifugoside H-1 was isolated together with cimicifugosides H-2-H-6 from commercial Cimicifugae Rhizoma. They are novel glycosides having a hydroxyl group ay C-11, and cimicifugosides H-3, H-4 and H-6 were trinor-triterpenol glycosides. Cimicifugoside H-1 changed into H-2, H-3 and H-4 under acidic or alkaline conditions. In this review, the structure elucidation of the above glycosides and their chemical transformation into other Cimicifuga glycosides are described.

Animals↗

[A study on the relationship between sources of health information concerning smoking and drinking, and health behavior].

To determine effective measures to popularize knowledge on the health effects of smoking and drinking and to change health behavior, an interview survey of 2000 persons aged 18 or older randomly chosen from national census forms throughout Japan was carried out. The coverage rates of the information concerning smoking and drinking were 97.3% and 92.5%, respectively. Television, newspapers and magazines were the major sources of health information concerning smoking and drinking. In addition, men who gave up or controlled smoking or drinking usually obtained health information from doctors, while those who had never controlled smoking usually obtained health information from their friends and families. Men who could not control drinking effectively usually obtained health information from the health examination consultant at the workplace. However, according to the answers from men who gave up or controlled drinking, the health information useful in changing health behavior was obtained from the health examination consultant at the workplace and from persons who had a disease history. Women who gave up or controlled drinking answered that the health information from their friends and families was helpful to change the health behavior.

Adolescent↗

Health and welfare statistics in Japan.

To abstract the health and welfare status of Japan, the essences of related statistics are referred and introduced. Those who want to know more detail are recommended to get a book "Health and Welfare Statistics in Japan" published by the government.

Female↗

Epidemiology of diseases of unknown etiology, specified as "intractable diseases".

In Japan, epidemiological studies on intractable diseases have been undertaken and greatly promoted for more than 20 years by the Research Committee on Epidemiology of Intractable Diseases, with the financial supports from the Ministry of Health and Welfare of Japan. In this paper, chronological history of development of the Research Committee and some scientific accomplishments by the recent Research Committee (1993-1995) were summarized, mainly focusing on descriptive, analytical and other epidemiological studies. Hoped is that the readers are to be acquainted with the recent research activities by the Research Committee and seek for possible international collaborations in epidemiological studies on intractable diseases.

Epidemiologic Methods↗

Bridged craniotomy for stable fixation of a bone flap. Technical note.

Postoperative depression of the bone flap is a common and bothersome problem in craniotomies. In this paper, a simple technique to avoid this deformity is described. The key to this technique is to leave uncut a part of each osteotomy approximately 5 mm in width as a "bridge" to the bone flap, which is then subsequently cut with the aid of a chisel. This technique provides stable fixation of the bone flap and satisfactory cosmetic results with little additional operating time.

Craniotomy↗

Poststatin, a new inhibitor of prolyl endopeptidase. VIII. Endopeptidase inhibitory activity of non-peptidyl poststatin analogues.

Non-peptidyl postatin analogues, (S)-N-substituted-2-[2-(1-acylpyrrolidinyl)]-2-oxoacetamides were synthesized and examined for their inhibitory activity against prolyl endopeptidase and cathepsin B in vitro. Many compounds showed stronger activity than natural poststatin, a pentapeptide. Among them, (S)-N-cyclohexyl-2-oxo-2-[2-(1-(3-phenoxybenzoyl)pyrrolidinyl)]ace tamide (22) and (S)-N-cyclohexyl-2-[2-(1-(2-naphthoyl)pyrrolidinyl)]-2-oxoacetamide++ + (19) indicated IC50 value of 5.8 and 8.2 ng/ml for prolyl endopeptidase inhibition respectively. None of these compounds possess significant inhibitory activities against cathepsin B, a cysteine protease. These results indicate that these compounds are more selective inhibitors against prolyl endopeptidase than is natural poststatin.

Magnetic Resonance Spectroscopy↗

Poststatin, a new inhibitor of prolyl endopeptidase. III. Optical resolution of 3-amino-2-hydroxyvaleric acid and absolute configuration of poststatin.

3-Amino-2-hydroxyvaleric acid was prepared, and separated into its diastereomers. The relative stereochemistry was determined by 1H NMR in their oxazolidone derivatives. The threo-isomer was resolved by (S)-1-(1-naphthyl) ethylamine in the N-(p-methoxybenzyloxycarbonyl) derivative. The absolute configuration of (--)-threo-3-(p-methoxybenzyloxycarbonyl)amino-2-hydroxyvaleric acid was confirmed to be 2R, 3S. The absolute configuration of 3-amino-2- oxovaleric acid in poststatin was confirmed to be S by comparison of the four stereoisomers of methyl N, O-bis(3,5-dinitrobenzoyl)-3-amino-2-hydroxyvalerate derived from 3-amino-2-hydroxyvaleric acid and that derived from 3-amino-2-oxovaleryl moiety of poststatin by means of HPLC with chiral column.

Amino Acid Sequence↗

Poststatin, a new inhibitor of prolyl endopeptidase. IV. The chemical synthesis of poststain.

Total synthesis of poststatin was achieved by both liquid phase and solid phase methods. In both methods, the (2R,3S)-3-amino-2-hydroxyvaleric acid moiety was incorporated into protected pentapeptides, and was oxidized to (S)-3-amino-2-oxovaleric acid (postine). Deprotection of the oxidized pentapeptides gave a specimen identical with natural poststatin in physico-chemical properties and prolyl endopeptidase inhibitory activity.

Amino Acid Sequence↗

Poststatin, a new inhibitor of prolyl endopeptidase. V. Endopeptidase inhibitory activity of poststatin analogues.

Thirty analogues of poststatin were synthesized, and their inhibitory activities against prolyl endopeptidase, human leukocyte elastase and cathepsin B were measured. The alpha-ketone was essential and the S configuration was preferable to the R configuration in the beta-substituted-beta-amino-alpha-oxopropionic acid moiety of poststatin analogues for endopeptidase inhibitory activity. The analogue in which the D-leucine residue of poststatin was replaced by L-leucine showed strong inhibitory activity to cathepsin B. Introduction of an aromatic group into the P4 position and proline into the P2 position increased inhibitory activity to elastase. Benzyloxycarbonyl-L-homophenylalanyl-(RS)- 3-amino-2-oxovaleryl-D-leucyl-L-valine was about 6 times more active to prolyl endopeptidase than natural poststatin.

Cathepsin B↗