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Biomedical subjects

N Minami

Publications and source records attributed to N Minami.

At least 145 records · Page 8Linked to original sources

Synthesis and biological evaluation of substituted benzenesulfonamides as novel potent membrane-bound phospholipase A2 inhibitors.

A novel series of 4-[N-methyl-N-[(E)-3-[4-(methylsulfonyl)phenyl]-2- propenoyl]amino]benzenesulfonamides has been prepared and evaluated as membrane-bound phospholipase A2 inhibitors. A structure-activity relationship study indicated that the optimum potency was realized with the N-(phenylalkyl)piperidine derivatives 3 and 4. These compounds inhibited the liberation of arachidonic acid from the rabbit heart membrane fraction with IC30 values of 0.028 and 0.009 microM, respectively. Several compounds (3, 4, and 28), which proved to be potent inhibitors in vitro, significantly reduced the size of myocardial infarction in coronary occluded rats by iv administrations prior to the ligation. N-(1-Benzyl-4-piperidinyl)-4-[N-methyl-N-[(E)-3-[ 4-(methylsulfonyl)phenyl]-2-propenoyl]amino]-benzenesulfonamide (3, ER-3826), which showed the protective in vivo effects at doses higher than 0.3 mg/kg iv, was finally chosen as a leading candidate.

Animals↗

Assessment of age-dependent changes in circadian blood pressure rhythm in patients with essential hypertension.

The effects of age on the circadian blood pressure rhythm of patients with untreated essential hypertension (n = 133, World Health Organization stage I or II) were compared with those of normotensive subjects (n = 91). Subjects were classified into three groups by age: young (less than 40 years old), adult (40-59 years old) and old (greater than or equal to 60 years old). Blood pressure was monitored every 5 min for 24 h, using a finger volume oscillometric device under fixed external conditions. The single cosinor method was used to evaluate circadian rhythm. There was no difference in the amplitude of circadian systolic or diastolic blood pressure rhythm among the different normotensive and essentially hypertensive age groups although a wide distribution of amplitude was noted within each group. The distribution of amplitude was wider in the hypertensive than in the normotensive groups. The amplitude of circadian blood pressure rhythm was independent of the mesor level. On the other hand, the amplitude of circadian heart rate rhythm decreased with increasing age both in normotensive subjects (P less than 0.05, young versus adult or old) and hypertensive patients (P less than 0.01, young and old versus adult). The acrophase of circadian systolic blood pressure rhythm in young hypertensives was greater than that in adult or old hypertensives (P less than 0.05, for both). Such age-dependent changes were not observed in the normotensive groups. Consequently, the acrophase of circadian systolic or diastolic blood pressure rhythm in young hypertensives was larger than that in young normotensives (P less than 0.05, for both systolic and diastolic blood pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Population study of ambulatory blood pressure in a rural community in northern Japan.

A cross sectional survey was performed on ambulatory blood pressure (ABP) in a rural community in northern Japan. ABP was measured in 468 participants (148 men and 320 women, or 27.3% of the less than or equal to 20 year-old population in the study region) with a Colin ABPM 630, an ABP monitoring system. ABP was determined every 30 min for 24 hr. All-day average of 24 hr ambulatory systolic, (SBP) and diastolic BP (DBP) in these subjects were 121.5 +/- 11.8 and 71.7 +/- 8.0 mmHg (mean +/- S.D.), respectively. Ambulatory SBP and DBP levels increased gradually with an increase in age in both sexes. The age dependent increase in SBP was, however, extremely small in men compared with that in the casual SBP of the ordinary Japanese reported. The minimal age-dependent increase in ambulatory SBP in men reflects a high ambulatory SBP in those below 50 years-old as well as a minimal increase in ambulatory SBP in those over 50. Ambulatory SBPs in women were lower than those in men until they reach the age of 50 years. Ambulatory SBP levels in men and women were similar after their 60's. Ambulatory DBP tended to fall or remain at the same level after 60 years-old. Thus, a greater pulse pressure was observed in elderly subjects. Casual SBP and DBP in the ordinary Japanese were significantly higher than the daytime average ambulatory SBP and DBP in all age groups of both sexes in the population except those in their 20's. The results suggests that ABP has different clinical characteristics and may have a different clinical significance from casual BP.

Adult↗

[An unusual case of superior sagittal sinus thrombosis accompanied with dural AV fistula].

Benign intracranial hypertension or pseudotumor cerebri is an collective term for a number of diverse syndromes characterized by increased intracranial pressure. Neither intracranial mass nor ventricular dilatation is observed in this disorder. Moreover, the pathogenesis of this syndrome has yet to be determined. We report a case of 36-year-old female diagnosed as benign intracranial hypertension, who has developed superior sagittal sinus thrombosis and dural AV fistula during the follow up period. The patient was pointed out to have papilledema and elevated intracranial pressure six years ago. Although she was examined by both DSA and CT scan, no abnormal intracranial lesions were observed. Consequently, she was diagnosed as the benign intracranial hypertension and had been followed as an out patient. Three years later, lumboperitoneal shunting was performed because of severe headache and visual impairment. Postoperatively, the patient had been well for two years. Recently, occipital headache recurred and she was readmitted to our hospital. MRI studies demonstrated dilated vessels in the right occipital area. Additionally, angiograms revealed not only the superior sagittal sinus thrombosis but also the rich network of dural AV fistula adjacent to the occlusion. According to those results, the superior sagittal sinus was supposed to have the incomplete occlusion or delayed blood flow that were not observed by DSA, MRI and CT scan performed previously. Those occlusive change in the superior sagittal sinus impeded the CSF absorption and elevated the pressure of venous inflow, then the arterio-venous communication has been developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Elevated plasma interleukin-6 in patient with idiopathic thrombocytopenic purpura].

Plasma Interleukin-6 (IL-6) level was measured in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), rheumatoid arthritis and aplastic anemia. Increase in the plasma level of IL-6 was observed in patients with ITP and SLE. The plasma IL-6 level decreased with progression of the treatment for ITP, and it showed weak negative correlations with the platelet count at the onset of ITP. The increases in the plasma IL-6 level suggest the involvement of activation of the immune system in the pathogenesis of ITP.

Adolescent↗

[The changes in von Willebrand factor multimer in a course of thrombotic thrombocytopenic purpura].

A 51 year-old woman with severe thrombocytopenia, hemolytic anemia, renal failure and loss of consciousness, and significant decrease in plasma large multimer of von Willebrand Factor (vWF) was diagnosed as having thrombotic thrombocytopenic purpura (TTP). She was treated with plasma exchange, anti-platelet agents and steroids. Although she showed temporary improvement and return of vWF multimer to a normal level, her symptoms reappeared, vWF large multimer level showed a remarkable increase, and she died because of pulmonary bleeding. It would be important that the vWF multimer bands changed in the course of TTP.

Female↗

A role for calmodulin in the growth of human hematopoietic progenitor cells.

A possible role for calmodulin in the colony growth of human hematopoietic progenitor cells was investigated using pharmacologic approaches. We obtained evidence for a dose-dependent inhibition of colony formation of myeloid progenitor cells (CFU-C) stimulated by interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte CSF (G-CSF) by three calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide hydrochloride (W-13), and trifluoperazine. Chlorine-deficient analogs of W-7 and W-13, with a lower affinity for calmodulin, did not inhibit the growth of CFU-C colonies. W-7, W-13, and trifluoperazine inhibited the colony formation of immature erythroid progenitor cells (BFU-E) stimulated by IL-3 plus erythropoietin (Ep) or GM-CSF plus Ep, in a dose-dependent manner, while they did not affect the colony formation of mature erythroid progenitor cells (CFU-E) induced by Ep. W-7, W-13, and trifluoperazine also led to a dose-dependent inhibition of GM-CSF-induced colony formation of KG-1 cells. Calmodulin-dependent kinase activity derived from the KG-1 cells was inhibited by these three calmodulin antagonists in a dose-dependent manner. These data suggest that calmodulin may play an important regulatory role via a common process in the growth of hematopoietic progenitor cells stimulated by IL-3, GM-CSF, and G-CSF. Mechanisms related to the growth signal of Ep apparently are not associated with calmodulin-mediated systems.

Bone Marrow Cells↗

Determination of clinical accuracy and nocturnal blood pressure pattern by new portable device for monitoring indirect ambulatory blood pressure.

The accuracy and clinical application of a new portable device for measuring ambulatory blood pressure (BP) (ABPM 630, Nippon Colin, Nagoya, Japan) were assessed. The device uses a conventional arm cuff inflated by CO2 gas from a compact cartridge and is based on a cuff-oscillometric as well as a Korotkoff sound (microphone) technique. Blood pressure values obtained by ABPM 630 were compared with those measured by the auscultatory method. With the microphone method the mean differences from the auscultatory method were -0.28 +/- 6.15 mm Hg (mean +/- SD) for SBP and 0.96 +/- 6.28 mm Hg for DBP (n = 256), while for the cuff-oscillometric method the mean differences were -1.77 +/- 6.07 mm Hg for SBP and 3.06 +/- 6.87 mm Hg for DBP (n = 297). There was a highly significant correlation between BP values measured by the auscultatory method and ABPM 630. In 40 untreated subjects, 24 h BP was monitored simultaneously with the ABPM 630 and with a finger volume-oscillometric device (UBP-100, UEDA, Tokyo, Japan). The daytime average of SBP with the former (126 +/- 11.6 mm Hg) was almost the same as that with the latter (123 +/- 16.0 mm Hg), while the nighttime average in the former (117 +/- 9.7 mm Hg) was significantly higher than that in the latter (108 +/- 14.1 mm Hg, P less than .01). Only 4 out of 40 subjects experienced no sleep disturbance from the arm-cuff inflation. Five of the 40 subjects complained that their sleep was frequently interrupted by the arm-cuff inflation.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗

Cardiovascular depression and stabilization by central vasopressin in rats.

The role of endogenous vasopressin in cardiovascular homeostasis was examined using vasopressin-deficient rats (Brattleboro) (n = 194) and their parent strain, Long-Evans rats (n = 181). Mean arterial pressure (blood pressure) and heart rate were measured every 4 seconds with or without infusion of drug solution for 21 hours, and mean values and their standard deviations (lability) were calculated. Blood pressure in Brattleboro rats (116 +/- 1.1 mm Hg, mean +/- SEM) was significantly higher than that in Long-Evans rats (96 +/- 0.7 mm Hg, p less than 0.001), whereas heart rates (381 +/- 3.3 and 375 +/- 2.9 beats/min, respectively) were similar. The lability of blood pressure and heart rate in Brattleboro rats (9.2 +/- 0.1 mm Hg and 42.3 +/- 0.7 beats/min) was also greater than that in Long-Evans rats (6.7 +/- 0.1 mm Hg, p less than 0.001 and 38.4 +/- 0.8 beats/min, p less than 0.01, respectively). In Brattleboro rats, intravenous vasopressin (0.1 ng/kg/min or 0.6 ng/kg/min) did not affect blood pressure, although it did reduce heart rate and decreased lability of blood pressure and heart rate. Intracerebroventricular (central) infusion of vasopressin (2 pg/kg/min) in Brattleboro rats induced initial hypertension and tachycardia followed by long-lasting hypotension and bradycardia, whereas in Long-Evans rats it induced only hypertension and tachycardia. In both strains, central vasopressin dramatically decreased the lability of blood pressure and heart rate. Neither intravenous (0.2 ng/kg/min) nor central desmopressin (2 pg/kg/min or 0.2 ng/kg/min), a V2 renal receptor agonist, changed any of these parameters in Brattleboro rats, although both diminished urinary volume. Neither intravenous (50 ng/kg/min) nor central (3.3 pg/kg/min) d(CH2)5-Tyr(Me)-arginine vasopressin, a vasopressin V1 receptor antagonist, modulated any of these parameters in Long-Evans rats. These results suggest that endogenous as well as exogenous vasopressin acts centrally as a cardiovascular inhibitor and stabilizer through a receptor mechanism other than V1 or V2 receptor mechanisms.

Animals↗

[Sex differences and regulatory mechanism of epidermal growth factor receptor in the rat liver].

The number of epidermal growth factor (EGF) receptor in rat hepatic membranes was about 2-hold higher in adult male than in adult female rats. Castration of adult males slightly decreased the EGF receptor number. Castration of neonatal males decreased the number of EGF receptors when they reached sexual maturity. This decrease was restored by the combination of neonatal and pubertal treatments with testosterone. Hypophysectomy caused a marked decrease in the number of EGF receptors in the male animals, and this decrease was not restored by either testosterone or triiodothyronine administration. Continuous administration of human growth hormone (hGH) with an osmotic minipump to normal males reduced the EGF receptor number. In contrast, intermittent administration of hGH twice a day (every 12 hr) to hypophysectomized males and/or normal females significantly increased the EGF receptor number. These results indicate that the number of EGF receptors in rat hepatic membranes is regulated by the secretory rhythm of GH in the pituitary, which may be "imprinted" by neonatal androgen.

Animals↗

Cosinor analysis of changes in circadian blood pressure rhythm with aging in spontaneously hypertensive rats.

Evolution of circadian rhythm of blood pressure with age in male spontaneously hypertensive rats (SHR) was compared with that in male Wistar Kyoto rats (WKY). Three different age groups (5-6 week old, 19-22 week old, 29-31 week old) were provided for each strain. Chronogram and cosinor method were used for time series analyses. In all age groups of WKY, a diurnal fall and a nocturnal rise in blood pressure (BP) as well as in heart rate (HR) were observed. There was no significant difference in acrophase between BP and HR in each age group of WKY. Regarding SHR, however, each age group demonstrated a different relation between circadian BP rhythm and HR rhythm. In 5-6 week old SHR, a difference in acrophase between BP and HR (about 6.9 hr, p less than 0.1) was observed, which became more conspicuous with the increase in age, eventually presenting an inverted relation between BP and HR in 19-22 week old SHR. The relation between circadian BP rhythm and circadian HR rhythm in 29-31 week old SHR was almost identical with that in 19-22 week old SHR. In other words, a phase lag of acrophase of BP from that of HR already observed in young SHR increased with aging. The results indicate that parasympathetic periodicity remained unchanged even in SHR since circadian HR rhythm was similar in all groups, while the periodicity of sympathetic neural tone relating to the regulation of circadian BP rhythm seems to be disturbed. The mechanism responsible for development and maintenance of high BP in SHR may be linked to a disturbance in the sympathetic mechanism which regulates BP periodicity.

Aging↗

[Properties of N-acetyl-beta-glucosaminidase in the masseter muscle of the mouse].

The present study was undertaken to clarify various characteristics of N-acetyl-beta-glucosaminidase (NAG) in the masseter muscle of the mouse. The pH optimum of NAG in tissue homogenate was 4.3, and Km value for p-nitrophenyl-N-acetyl-beta-glucosaminide was 0.98 mM. By means of isoelectric focusing. NAG in the masseter muscle was separated into four enzymes (NAG I-IV). The isoelectric points were: I, 4.9; II, 6.4; III, 7.2 and IV, 8.7. The pH optima of NAG I-IV ranged from 4.2 to 4.4, and Km values from 0.61 to 0.83 mM. The molecular weights of I, II, III and IV were 135,000, 120,000, 135,000 and 110,000, respectively. Studies on heat stability showed that NAG I and IV were slightly labile as compared with II and III. The activities of NAG I-IV were dose dependently inhibited by both N-acetyl-glucosamine and N-acetyl-galactosamine. Both Ag and Hg2+ ions caused a marked inhibition on activities of NAG I-IV.

Acetylglucosaminidase↗

Influence of age on the nocturnal fall of blood pressure and its modulation by long-acting calcium antagonists.

The clinical significance of the nocturnal fall of blood pressure (BP) was examined. BP was monitored every 5 min for 24 hrs by means of a finger volume oscillometric device. The nocturnal fall was observed in all age groups (young: less than 40, n = 49; adult: 40 less than or equal to less than 60, n = 110; old: 60 less than or equal to, n = 33). The amplitude of nocturnal fall of BP (averaged daytime blood pressure--averaged nighttime blood pressure) in old patients (systolic = 13 +/- 11, diastolic = 10 +/- 8 mmHg, mean +/- SD) was similar to that in the young patients (systolic = 11 +/- 8, diastolic = 10 +/- 8 mmHg). These 192 subjects were also classified according to mean BP level (MBP) averaged for daytime in the ambulatory blood pressure monitoring records [MBP less than 85 (mmHg), n = 31; 85 less than or equal to MBP less than 100, n = 72; 100 less than or equal to MBP less than 115, n = 49; 115 less than or equal to MBP, n = 25]. BP level did not affect the pattern of circadian variation in the normal subjects or in the essential hypertensive patients at WHO stage I or II. The amplitude of the nocturnal fall in systolic BP increased with the increase in BP level, but this was not the case with diastolic BP (mean daytime BP less than 85 mmHg: systolic = 11 +/- 8, diastolic = 8 +/- 6 mmHg; 85 less than or equal to less than 100: systolic = 14 +/- 8, diastolic = 11 +/- 6 mmHg; 100 less than or equal to less than 115: systolic = 17 +/- 9, diastolic = 11 +/- 8; 115 less than or equal to: systolic 17 +/- 8, diastolic = 11 +/- 6 mmHg). Nitrendipine (8.6 +/- 5.6 mg, 22.5 +/- 11.4 days, n = 14) and nisoldipine (9.3 +/- 6.2 mg, 21.5 +/- 11.4 days, n = 15) administered once daily in the morning or nifedipine slow release tablet, 20 mg twice daily (n = 15, 17.7 +/- 5.2 days) induced a significant downward shift in the circadian BP pattern, in other words, the hypotensive effect was also observed during the night when the BP had already been low. Taken together, the information on the nocturnal behavior of BP would be valuable, especially in treating aged patients with essential hypertension with a long-acting antihypertensive drug.

Aging↗

A cross-sectional survey of home blood pressure in a rural community in northern Japan.

A cross-sectional survey was performed on home blood pressure recordings (home BP) in a rural community in northern Japan. In total, 1190 participants (495 men and 695 women which consist 61.5% of the greater than or equal to 15 year-old regional population, n = 1933) were asked to measure home BP every morning for a month, using a semiautomatic BP measuring device. The actual measurements were done 16.8 +/- 10.2 times (mean +/- SD) for men and 19.0 +/- 9.4 times for women. Home systolic (SBP) and diastolic BP (DBP) was elevated gradually with age in both sexes, although DBP tended to fall after reaching 70 years old in men. SBP and DBP thus measured were significantly lower than those of casual BP of ordinary Japanese people reported by the Ministry of Health and Welfare, Japan, by 11.4 +/- 4.3 mmHg SBP (mean +/- SD) and 5.9 +/- 1.6 mmHg DBP in men, and 12.7 +/- 5.1 mmHg SBP and 8.1 +/- 2.5 mmHg DBP in women. When WHO criteria were applied to the home BP, 2.8% of men and 0.6% of women were considered to be definitely hypertensive, and 7.9% of men and 6.4% of women as of borderline cases, indicating the underestimation of hypertensive population by means of home BP. Based on these data, we demonstrated the values equal to 1SD or 2SDs above the mean in each age group to tentatively determine biological normalcy. It is necessary to define the relationship between home BP and target organ disease or hypertensive complications. A long-term prospective study is also necessary to define the relationship between home BP and long-term morbidity or mortality.

Adolescent↗