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Biomedical subjects

N Minami

Publications and source records attributed to N Minami.

At least 109 records · Page 6Linked to original sources
PubMed1993

cDNA nucleotide sequence and primary structure of mouse uterine peptidylarginine deiminase. Detection of a 3'-untranslated nucleotide sequence common to the mRNA of transiently expressed genes and rapid turnover of this enzyme's mRNA in the estrous cycle.

Peptidylarginine deiminase is a protein-modulating enzyme which converts the arginine residues in proteins to citrulline residues. This study describes the complete primary structure of mouse peptidylarginine deiminase, which was deduced from nucleotide sequence analysis of cDNA clones plus proteochemical analysis of the purified enzyme. The composite cDNA sequence contained a 5' untranslated region of 7 bases, an open reading frame of 2019 bases that encoded 673 amino acids, a 3' untranslated region of 2662 bases, and part of a poly(A) tail. The N-terminal and C-terminal sequences of the enzyme matched the sequences deduced from nucleotide analysis. Furthermore, we determined that the N-terminal sequence was N alpha-acetyl-Met-Gln-, a sequence which has never previously been reported among N alpha-acetyl-Met proteins. The Arg 352 of the enzyme was converted to a citrulline residue and the potential Asn-linked glycosylation site (Asn542-Glu543-Ser544) had no carbohydrate moiety. Thus, mouse peptidylarginine deiminase consists of 673 amino acids with a molecular mass of 76,260. Mouse peptidylarginine deiminase mRNA has two AU-rich structures in the 3' untranslated region which exhibit a high degree of similarity to those in lymphokine, cytokine and proto-oncogene mRNA species. Since the rat enzyme (previously reported) does not possess these characteristic structures, we compared the levels of enzyme activity and mRNA in the mouse and rat uterus at four defined phases of the estrous cycle. The degradation of peptidylarginine deiminase and its mRNA proceeded significantly faster in the mouse than in the rat. We speculate that the unusual structure of the mouse enzyme and its mRNA be involved in this species-specific rapid degradation.

Amino Acid Sequence↗
PubMed1993

Increased levels of vascular endothelial cell markers in thrombotic thrombocytopenic purpura.

We found that patients with thrombotic thrombocytopenic purpura (TTP) have significantly elevated plasma thrombin antithrombin III complex (TAT) and FDP-D-dimer levels, while the plasmin-alpha 2 plasmin inhibitor complex (PIC) level was only slightly increased. The tissue-type plasminogen activator (t-PA) level was increased, but it was well correlated with the plasminogen activator inhibitor-I (PAI-I) level. These findings suggest that hypercoagulable and hypofibrinolytic states coexist in these patients, in contrast to patients with disseminated intravascular coagulation, who exhibit coexisting hypercoagulable and hyperfibrinolytic states. Levels of vascular endothelial cell markers, such as PAI-I, thrombomodulin (TM), and t-PA, were increased at the onset of TTP, but the level of von Willebrand factor (vWF) antigen was not increased. The outcome in TTP patients was correlated with plasma t-PA and TM levels but not with TAT or PIC. These results suggest that vascular endothelial cell markers, such as TM and t-PA, are released from injured or stimulated endothelial cells, reflecting the degree of vascular endothelial damage, and that the main factor in the pathogenesis of TTP is vascular endothelial cell injury.

Adolescent↗
PubMed1993

Effects of cicletanine on the urinary excretion of prostanoids and kallikrein, and on renal function in man.

The effects of cicletanine, a new antihypertensive agent, on the prostaglandin-kallikrein system and the renin-angiotensin system were studied. A single oral dose of 200 mg cicletanine or placebo was administered to 9 healthy male volunteers, with samples of blood and urine obtained before and 2 hours after drug administration. Cicletanine increased the urine flow, urinary excretion of sodium, and fractional excretion of sodium by 47%, 115%, and 104%, respectively. While the excretion of 6-keto-prostaglandin-F1 alpha was enhanced significantly, urinary excretion of thromboxane-B2, prostaglandin-E2, and kallikrein were unchanged. Cicletanine also did not alter plasma renin activity, plasma aldosterone concentration, or creatinine clearance. These observations suggest that cicletanine may suppress sodium reabsorption at the nephron, and it may stimulate prostacyclin generation with no effect on that of thromboxane-A2. Thus cicletanine may be beneficial in the management of cardiovascular disorders in which the equilibrium between prostacyclin and thromboxane is disturbed.

Administration, Oral↗
PubMed1993

Age-specific characteristics of nocturnal blood pressure in a general population in a community of northern Japan.

The age- and gender-specific profile of circadian blood pressure variation was examined by monitoring ambulatory blood pressure (ABP) in 477 untreated subjects in a rural community of northern Japan. Autoregressive spectral analysis demonstrated three major peaks at around 24, 12, and 8 h. We fitted a truncated Fourier series with three harmonics to the blood pressure (BP) data using least squares regression. More than half of the BP and pulse rate periodic curves were bimodal, one-third were trimodal, and the remainder were unimodal. The nadir of BP appeared between 00:00 and 01:30, and that of pulse rate occurred between 00:30 and 02:00. The nadir of systolic and diastolic BP, as well as pulse rate, appeared earlier with increasing age, and the difference between subjects in their 20s and those in their 70s was about 1 h. The amplitude of 24 h BP decreased with increasing age in men, but not in women. This type of information on the circadian BP profile of a general population is useful for the diagnosis and treatment of hypertension.

Adult↗
PubMed1993

Increased expression of cofilin in dystrophic chicken and mouse skeletal muscles.

A monoclonal antibody (McAb) specific for actin depolymerizing factor (ADF) was prepared. With this and previously prepared anti-cofilin McAb (MAB-22) and other antibodies, the expression of cofilin and ADF in the muscles of dystrophic (NH-413) chicken and dystrophic (C57BL/6J dy/dy) mice was compared with that in normal control animals by immunoblotting and immunocytochemical methods. Since cofilin expression is down-regulated during normal postnatal development of skeletal muscles [Abe et al. (1989) J. Biochem. 106, 696-702], cofilin was detected in the breast (pectoralis) muscle of normal adult chicken and the leg (femoris and tibialis anterior) muscles of normal mice only at a low level. ADF was not detectable in adult skeletal muscles. However, a significant increase of cofilin amount, but not of ADF amount, was observed in these muscles of the dystrophic animals, when the symptom of muscular dystrophy became evident. In order to localize cofilin in individual muscle fibers, serial cryosections of the dystrophic chicken muscle were examined with anti-cofilin antibody (MAB-22). The antibody stained cells of different size in the dystrophic muscle, indicating that cofilin expression was induced in the regenerating muscle cells as well as in the pre-existing myofibers. We suggest that cofilin is involved in disassembly or reorganization of actin in the dystrophic muscle.

Actin Depolymerizing Factors↗
PubMed1993

Relationship between cardiovascular hypertrophy and cardiac baroreflex function in spontaneously hypertensive and stroke-prone rats.

OBJECTIVE: To determine whether the reduced baroreceptor-heart rate reflex sensitivity in genetically hypertensive rats is related to the level of cardiac or vascular hypertrophy. DESIGN: Young spontaneously hypertensive rats (SHR), stroke-prone hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats were treated chronically with the angiotensin converting enzyme (ACE) inhibitor perindopril in different regimens in order to produce a wide-ranging combination of cardiac and vascular hypertrophy. METHODS: All strains were treated with perindopril (0.1, 0.3, 1 or 3 mg/kg per day) in their drinking water from 4 until 9 weeks of age. Additional groups of SHR were treated with perindopril (3 mg/kg per day) from 4 until 12 weeks and from 4 until 14 weeks of age. At 13 weeks of age all animals were chronically instrumented with arterial and venous catheters. One week later, steady-state sigmoidal mean arterial pressure-heart rate reflex curves were obtained in the conscious rats by the injection of pressor and depressor agents before and after the administration of atenolol (1 mg/kg, intravenously) to determine the vagal component. The minimum and the maximum blood pressure produced by nitroprusside and methoxamine, respectively, after simultaneous ganglion and beta-adrenoceptor blockade were used as an index of whole body vascular hypertrophy. The left ventricular to body weight ratio was measured at the end of the experiment. RESULTS: At 14 weeks of age, mean arterial pressure, the maximum and minimum autonomically blocked blood pressure and the left ventricular to body weight ratio were 34, 20, 9 and 17% higher, respectively, in SHR, and 56, 35, 27 and 39% higher, respectively, in SHRSP than in WKY rats. Perindopril treatment dose-dependently reduced both cardiac and vascular hypertrophy but to different extents. The highest doses reduced mean arterial pressure and the autonomically blocked maximum and minimum blood pressure in both hypertensive strains to the levels of untreated WKY rats but approximately 50% of the cardiac hypertrophy was still present. The left ventricular to body weight ratio was normalized in SHR only with the longer term perindopril treatments. A comparison of the baroreflex function curves in untreated SHR and SHRSP showed that the vagal component of the heart rate range was markedly reduced compared to that in WKY rats. Treated SHRSP had a normal mean arterial pressure and a normal autonomically blocked maximum and minimum blood pressure, but their vagal heart rate range was only 63% of that in WKY rats. The heart rate range in SHR treated from 4 to 9 weeks of age was only marginally greater than that of untreated SHR, despite prevention of hypertension and vascular hypertrophy. In SHR treated from 4 until 12 weeks of age, which prevented cardiac hypertrophy, the vagal heart rate range was markedly greater. With perindopril from the age of 4 to 14 weeks, the vagal baroreflex heart rate range was similar to that of WKY rats. Thus the improvement in the vagal heart rate range was more closely related to the prevention of cardiac hypertrophy (r = 0.73, P < 0.001) than vascular hypertrophy or a blood pressure elevation. Since there were no further changes in the indices of hypertrophy, the presence of the ACE inhibitor was likely to have been responsible for restoring the remaining 35% of the vagal baroreflex not affected by structural factors. CONCLUSIONS: These results suggest that prevention of cardiac rather than vascular hypertrophy is the major requirement for normalizing the vagal component of the baroreceptor-heart rate reflex in hypertensive rats. However, structural changes accounted for only about two-thirds of the vagal deficit. The remainder was restored by the presence of an ACE inhibitor, suggesting that the vagal component of the baroreceptor-heart rate reflex is normally suppressed by the renin-angiotensin system.

Animals↗
PubMed1993

Characteristics of a community-based distribution of home blood pressure in Ohasama in northern Japan.

OBJECTIVE: To evaluate the distribution, reference values and day-to-day variation of blood pressure of untreated subjects measured at home. DESIGN: Cross-sectional study of a cohort. SETTING: General community in northern Japan. SUBJECTS: Blood pressure was measured in 871 subjects (mean +/- SD age 46.0 +/- 19.5 years, range 7-98, constituting 38.7% of the local population of Uchikawama region, Ohasama) who were not receiving antihypertensive medication. METHODS: Subjects measured their own blood pressure at home at least three times (mean +/- SD 19.7 +/- 8.4) each morning using a semi-automatic oscillometric blood pressure measuring device. Screening blood pressure was measured once. MAIN OUTCOME MEASURES: Distribution of home blood pressure in the study population as a whole and with respect to age and sex, and the distribution of day-to-day variation of home blood pressure were determined. RESULTS: Mean home blood pressure was 117.3 +/- 13.4/69.3 +/- 9.7 mmHg (95% confidence interval 116.4-118.2/68.7-70.0). The 95th centile value was 143/85 mmHg, mean+SD 131/79 mmHg and mean + 2SD 144/89 mmHg. Mean screening blood pressure was 126.2 +/- 18.9/72.1 +/- 11.7 mmHg (95th centile 159/92 mmHg). Age- and sex-specific 95th centile values as well as mean +/- SD were obtained. Mean+SD, mean + 2SD and the 95th centile values obtained as reference upper limits of home blood pressure from subjects identified as normotensive by screening blood pressure (n = 707) were 125/77, 137/86 and 134/83 mmHg, respectively. Home blood pressure increased gradually with increasing age in both men and women, although blood pressure was significantly higher in men until 50 years of age. Day-to-day variation of home systolic blood pressure also increased with age. CONCLUSION: Since the distribution of home blood pressure values was affected by age and sex, age- and sex-matched reference values for home blood pressure should be established. Home blood pressure values in elderly subjects should be evaluated carefully, since these exhibit greater day-to-day variation.

Adolescent↗
PubMed1993

Hot water epilepsy with pineal cyst and cavum septi pellucidi.

A case of reflex epilepsy accompanied by pineal cyst and cavum septi pellucidi induced by hot water bathing is presented. The patient is a 25-year-old male who has had six episodes of convulsions during the last three years. The seizures were diagnosed as a complex partial epilepsy followed by generalized tonic seizures. We have succeeded in recording his electroencephalogram (EEG) during convulsions. Moreover, a magnetic resonance imaging (MRI) study revealed a pineal cyst and cavum septi pellucidi. This is quite a rare form of adult hot water epilepsy accompanied by intracranial malformations.

Adult↗
PubMed1993

Ambulatory blood pressure of adults in Ohasama, Japan.

We performed a cross-sectional study in a small town in northern Japan to evaluate the distribution, reference values, and daily variation in ambulatory blood pressure. A total of 705 subjects (229 men aged 61.3 +/- 13.4 years [mean +/- SD] and 476 women aged 57.5 +/- 13.3 years; 41.1% of the regional adult population, n = 1716), including those treated with antihypertensive drugs (n = 231, 66.5 +/- 9.5 years) as well as untreated subjects (n = 474, 55.0 +/- 13.5 years), participated in the study. Both ambulatory and screening blood pressures were measured in 659 subjects. Ambulatory blood pressure was measured with an automatic device (Colin ABPM-630). The 24-hour ambulatory blood pressure in the total population was 121.7 +/- 13.0/71.1 +/- 7.6 mm Hg (95th percentile value [95%] = 146/85 mm Hg). The corresponding value in the untreated subjects was 119.4 +/- 12.5/70.1 +/- 7.4 mm Hg (95% = 144/83 mm Hg). The 24-hour average ambulatory blood pressure was 118.0 +/- 11.1/69.4 +/- 6.8 mm Hg (95% = 139/81 mm Hg) in subjects identified as normotensive by their screening blood pressure (n = 448, 57.2 +/- 13.1 years) and 133.6 +/- 14.2/78.9 +/- 8.8 mm Hg in those identified as hypertensive by their screening blood pressure (n = 73, 63.1 +/- 10.6 years). Based on the mean+SD of the 24-hour ambulatory blood pressure in the normotensive subjects by their screening blood pressure (129/76 mm Hg), the 24-hour ambulatory blood pressures in 25 (34.2%) of these 73 hypertensive subjects by screening blood pressure were below this level. Nine (2%) of 448 normotensive subjects by screening blood pressure were above the mean+2 SDs (140/83 mm Hg) of the 24-hour ambulatory blood pressure in the normotensive group by screening blood pressure. Ambulatory and screening blood pressures increased with age. The age-dependent increase in ambulatory blood pressure was less apparent in men. The 24-hour average pulse rate decreased with age. The daily variation in ambulatory blood pressure (standard deviation) increased with age, whereas that of pulse rate decreased with age. Increases in blood pressure variation were observed in nighttime and daytime blood pressure values. The differences between day versus night ambulatory blood pressures decreased with age in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Immunoblotting of contractile and cytoskeletal proteins of canine basilar artery in vasospasm.

Vasospasm was produced in the canine basilar arteries by a two-hemorrhage method, and voltage- and receptor-dependent contractions of the normal canine basilar arteries were induced by local applications of potassium chloride (KCI) and serotonin, respectively, after transclival exposure. Actin, myosin, desmin, filamin, talin, vinculin, and alpha-actinin in the basilar artery were studied by immunoblotting. The immunoblots showed a decrease or loss in immunoreactivity of some native proteins and generation of protein fragments, smaller in size than native proteins, in spastic, KCI, and serotonin groups, indicating a proteolytic degradation. In the spastic group on Day 2, actin, desmin, and filamin were usually degraded slightly; myosin moderately; and talin and alpha-actinin substantially. Vinculin and metavinculin remained intact. In the spastic group on Day 7, actin and desmin were usually decomposed slightly; myosin, filamin, and vinculin substantially; and talin, metavinculin, and alpha-actinin markedly. In the KCI and serotonin groups, slight degradation was usually observed in filamin, often in alpha-actinin, and occasionally in actin, whereas desmin, vinculin, and metavinculin were not degraded. In addition, myosin was usually degraded moderately in the KCI group and slightly in the serotonin group, and talin was generally decomposed slightly in the KCI group and moderately in the serotonin group. The degraded fragments, although variable in number and immunoreactivity, were similar in size in the three groups. We suggest that the intracellular devices responsible for contraction of the basilar arteries are degraded more severely in the spastic group than in the KCI or serotonin group, probably by similar proteolytic mechanism and progressively with the passage of time after subarachnoid hemorrhage in vasospasm.

Animals↗
PubMed1993

Calpain-calpastatin system of canine basilar artery in vasospasm.

Vasospasm was produced in the canine basilar artery by a two-hemorrhage method, while contraction was induced in the normal canine basilar artery by a local application of KCl or serotonin after transclival exposure. The control animals were injected with saline instead of fresh blood. The activation of mu-calpain, a Ca(++)-dependent neutral protease, in the basilar artery was studied by evaluating the conversion from its inactivated into its activated form on immunoblots. In addition, the activity of calpastatin, an intrinsic inhibitor of calpain, in the basilar artery was determined by assay. The majority of the mu-calpain was inactivated in the control group. In the spastic group, mu-calpain was generally activated markedly in the early stage of vasospasm and moderately thereafter. The contraction induced by KCl or serotonin application was classified into the early phasic and the later tonic stages; mu-calpain was usually activated in the phasic stage and inactivated in the tonic stage. Calpastatin activity was significantly decreased during vasospasm, whereas it was not significantly changed in KCl- or serotonin-induced contraction. The final activity of mu-calpain results from the balance of mu-calpain and calpastatin. This suggests that mu-calpain activity was enhanced continuously in the spastic group and transiently in the KCl or serotonin group, and that the continuous activation of mu-calpain during vasospasm probably induced more proteolytic changes compared to those in the KCl or serotonin group.

Animals↗
PubMed1993

[Cytokine levels in patients with thrombotic thrombocytopenic purpura].

Plasma cytokine levels were examined in 13 patients with thrombotic thrombocytopenic purpura (TTP). Complete remission (CR) was attained in 7 of the 13 patients, but 6 died. Tumor necrosis factor (TNF), Interleukin (IL)-1, IL-6 and soluble IL-2 receptor showed marked increases at onset and decreased at CR. The prognosis tended to be poor in patients with increased IL-6 and soluble IL-2 receptor levels. Tissue factor production in human umbilical vein endothelial cell (HUVEC) cultured with TTP plasma was significantly increased, but the migration of HUVEC to TTP plasma was significantly lower. These findings suggest that immunological mechanisms and vascular endothelial cell damages are involved in the pathogenesis of TTP and are reflected in the plasma cytokine levels.

Adolescent↗
PubMed1993

[A case of primary intracranial malignant lymphoma presenting opsoclonus-polymyoclonia syndrome].

A 46-year-old woman was doing well until December 1989, when she noted vertigo and difficulty in walking. She was admitted to our department on February, 7, 1990. General physical examination was unremarkable. Neurological examination revealed opsoclonus, limbs and truncal ataxia, and myoclonus over the facial muscle, neck, and all the extremities, suggestive of opsoclonus-polymyoclonia syndrome. Other neurological finding was not apparent. T2 weighted MRI (Siemens 1.5 Tesla) showed abnormal high intensity area without mass effect at the dentate nucleus of left cerebellum. She was treated with 60 mg of oral prednisolone, followed by gradual improvement of her neurological signs and abnormal MRI findings. However, in May, she gradually developed right hemiparesis, consciousness disturbance and pseudobulbar palsy. MRI showed multiple abnormal intensity area at left frontal lobe, right basal ganglia, and right cerebellar hemisphere. Open brain biopsy from the left frontal lesion revealed malignant lymphoma (diffuse large cell type, B cell type). She was treated by radiation therapy at the dose of 50 Gy (whole brain 40 Gy, local 10 Gy) with subsequent disappearance of opsoclonus, myoclonus, and ataxia. To our knowledge, this is the first case of primary intracranial malignant lymphoma presenting opsoclonus-polymoclonia syndrome.

Brain Neoplasms↗
PubMed1992

Localization of smg p25A/rab3A p25, a small GTP-binding protein, at the active zone of the rat neuromuscular junction.

smg p25A is a small G protein which has been suggested to regulate neurotransmitter release from the synapses. We investigated here the ultrastructural localization of this small G protein in the rat neuromuscular junction by an immunoperoxidase method. The results showed that smg p25A was distributed non-uniformly on the presynaptic plasma membrane and among the synaptic vesicles with the focal accumulation on the discrete presynaptic sites which corresponded to the active zones, the regions of the presynaptic plasma membrane specialized for the exocytosis of the synaptic vesicles. This unique distribution of smg p25A suggests that it plays an important role in the attachment and fusion of the synaptic vesicles with the active zones.

Animals↗
PubMed1992

Importance of cardiac, but not vascular, hypertrophy in the cardiac baroreflex deficit in spontaneously hypertensive and stroke-prone rats.

In the present study, we examined whether antihypertensive treatment of young and adult hypertensive rats with the angiotensin-converting enzyme (ACE) inhibitor perindopril could restore the baroreflex vagal deficit and whether this was related to prevention of cardiac or vascular hypertrophy. Spontaneously hypertensive (SHR), stroke-prone spontaneously hypertensive (SHR-SP), and Wistar-Kyoto (WKY) rats were untreated or treated with perindopril (3 mg/kg/day) in the drinking water from 4-9 and from 14-20 weeks of age. Steady-state sigmoidal mean arterial pressure (MAP)-heart rate (HR) reflex curves were obtained in the conscious rats by the injection of pressor and depressor agents before and after atenolol (vagal component). Increased left ventricle to bodyweight ratio (LV/BW) indicated cardiac hypertrophy. After ganglion blockade, the minimum MAP produced by nitroprusside and the maximum produced by methoxamine were used as indications of vascular hypertrophy. Perindopril treatment reduced cardiac and vascular hypertrophy to different extents in SHR and SHR-SP. The 4-9 and 14-20 week treatments reduced MAP and both minimum and maximum blood pressure of the SHR to the levels of the untreated WKY. However, only in the older animals was LV/BW restored. In the SHR-SP, early treatment had a much greater effect on vascular hypertrophy than on LV/BW. The reverse occurred for the 14-20 week animals. In untreated hypertensive animals the baroreflex curves were shifted to the right with reduced vagal HR range. Perindopril treatment shifted the baroreflex curves back towards the WKY curves. Vagal HR range was strongly correlated with the LV/BW, whereas vagal HR range was less well related to the level of vascular hypertrophy or blood pressure. These results suggest that antihypertensive treatment can restore cardiac baroreflex function and that it is related to the reduction in cardiac hypertrophy. Although the mechanism of this relationship remains to be elucidated, these findings suggest that cardiac vagal afferents may be important.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Recent duplication of the two human CD8 beta-chain genes.

Isolation of cDNA clones encoding the beta-chain of the human T cell surface glycoprotein CD8 revealed the presence of five distinct forms of cDNA resulting from alternative splicing. In the process of analysis of the gene organization, we found that there exist two recently duplicated genes for CD8 beta. These genes, designated CD8 beta 1 and beta 2, consist of nine and seven exons, respectively. The organization of CD8 beta 1 and beta 2 genes is almost identical except in their 3'-ends. There are nine nucleotide differences between the coding regions of the CD8 beta 1 and beta 2 genes in spite of the extremely high similarity of these genes which extends over the entire genes including introns. Pulse field gel analysis demonstrated that CD8 beta 1 and beta 2 genes are located more than 1.5 Mb apart. It was found that the CD8 beta 1 gene is approximately 25 kb upstream from the CD8 alpha gene in the same transcriptional orientation on chromosome 2. Although both CD8 beta 1 and beta 2 genes appear functional from the nucleotide sequence, the five distinct forms of CD8 beta cDNAs and corresponding mRNAs found in thymus, PBL, and leukemic cell line HPB-ALL are all derived by alternative splicing from CD8 beta 1 transcripts.

Amino Acid Sequence↗