PubMed Health⌕ Search

Biomedical subjects

K Omata

Publications and source records attributed to K Omata.

At least 37 records · Page 2Linked to original sources
PubMed1999

Therapeutic advantage of angiotensin converting enzyme inhibitors in chronic glomerulonephritis.

Hypertension in chronic progressive renal disease is a major clinical problem leading to renal function loss. We studied the influence of ambulatory blood pressure (ABP) and the effect of hypertension therapy on renal function in 116 patients with chronic glomerulonephritis. Patients were subdivided as hypertensive, normotensive and hypotensive according to the level of ABP and age. Hypotensive subjects showed improvement of renal function and normotensive subjects showed slower rate of progression of renal function loss than hypertensives, suggesting the adequate level of ABP was 100-125/55-75 mm Hg in patients less than 40 years old, 100-135/60-80 mm Hg in patients 40-60 years old, and 105-140/60-85 mm Hg in patients over 60 years, respectively. The renal protection of calcium antagonists was associated with achieving lower blood pressure levels, whereas the blood pressure level did not affect progression of renal function in patient treated with angiotensin converting enzyme (ACE) inhibitor. ACE inhibitor, but not calcium antagonists, showed a reduction of urinary protein excretion. Thus, the mechanisms of renal protection were different between ACE inhibitors and calcium antagonists.

Adolescent↗
PubMed1999

[Effect of adenosine on isolated afferent arterioles].

We investigated the direct effect of adenosine on afferent arterioles (Af-Arts) and the receptor subtype that mediates the constrictor or dilator action of adenosine. Af-Arts were isolated from the superficial cortex of rabbit kidney and perfused in vitro. Adenosine added to either the lumen or bath constricted the Af-Arts in a dose-dependent manner. This constriction was blocked by the A1 receptor antagonist, 6-oxo-3-(2-phenylpyrazole(1,5-a)pyridin-3-yl)-1 (6H)-pyridazinebutyric acid (FK838) or 8-cyclopentyl-1, 3-dipropylxanthine(DPCPX). We also examined the effect of adenosine on preconstricted Af-Arts with norepinephrine. Adenosine added to either the lumen or bath further constricted the preconstricted Af-Arts. In the presence of FK838, adenosine added to either the lumen or bath dilated the preconstricted Af-Arts, but in a different dose-dependent manner. Adenosine-induced dilation was inhibited by the A2 receptor antagonist, 3, 7-dimetyl-1-propargylxanthine(DMPX). These data indicate that adenosine constricts Af-Arts via A1 receptors and that adenosine dilates preconstricted Af-Arts via A2 receptors when A1 receptors are blocked.

Adenosine↗
PubMed1999

Immunohistochemical estimations of growth activity to predict biological behavior of pheochromocytomas.

To determine the usefulness of immunohistochemical estimations of growth activity to predict biological behavior of pheochromocytomas (PC), 42 cases of PC (33 adrenal and nine extra-adrenal tumors) were studied by immunohistochemistry using the monoclonal antibody, MIB-1. The mean MIB-1-positive cell rate for all 42 PCs was low (1.4%). The MIB-1-positive cell rates of adrenal PCs were significantly higher in malignant tumors (mean, 3.30%) than in benign tumors (mean, 0.81%) (P = .0184). In extra-adrenal PCs, the difference between benign (mean, 0.44%) and malignant (mean, 5.10%) tumors was also statistically significant (P = .0004). Other clinicopathologic factors, including family history, age, sex, and multiple endocrine neoplasm (MEN) type II status were also examined and were not statistically significant. In conclusion, estimation of the MIB-1-positive cell rate is useful for histologic distinction between benign and malignant pheochromocytomas. Especially, it is important to note that a high MIB-1-positive cell rate (>2%) is highly suggestive of malignancy.

Adolescent↗
PubMed1998

Carbon beam dosimetry intercomparison at HIMAC.

To verify international uniformity in carbon beam dosimetry, an intercomparison programme was carried out at the heavy ion medical accelerator (HIMAC). Dose measurements with ionization chambers were performed for both unmodulated and 6 cm modulated 290 MeV/nucleon carbon beams. Although two different dosimetry procedures were employed, the evaluated values of absorbed dose were in good agreement. This comparison established a common framework for ionization chamber dosimetry between two different carbon beam therapy facilities.

Carbon↗
PubMed1997

Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole.

Although angiotensin II type 2 (AT2) receptor has recently been cloned, its functional role is not well understood. We tested the hypothesis that selective activation of AT2 receptor causes vasodilation in the preglomerular afferent arteriole (Af-Art), a vascular segment that accounts for most of the preglomerular resistance. We microperfused rabbit Af-Arts at 60 mmHg in vitro, and examined the effect of angiotensin II (Ang II; 10(-11)-10(-8) M) on the luminal diameter in the presence or absence of the Ang II type 1 receptor antagonist CV11974 (CV; 10(-8) M). Ang II was added to both the bath and lumen of preconstricted Af-Arts. Ang II further constricted Af-Arts without CV (by 74+/-7% over the preconstricted level at 10(-8) M; P < 0.01, n = 7). In contrast, in the presence of CV, Ang II caused dose-dependent dilation; Ang II at 10(-8) M increased the diameter by 29+/-2% (n = 7, P < 0.01). This dilation was completely abolished by pretreatment with an AT2 receptor antagonist PD123319 (10(-7) M, n = 6), suggesting that activation of AT2 receptor causes vasodilation in Af-Arts. The dilation was unaffected by inhibiting either nitric oxide synthase (n = 7) or cyclooxygenase (n = 7), however, it was abolished by either disrupting the endothelium (n = 10) or inhibiting the cytochrome P-450 pathway, particularly the synthesis of epoxyeicosatrienoic acids (EETs, n = 7). These results suggest that in the Af-Art activation of the AT2 receptor may cause endothelium-dependent vasodilation via a cytochrome P-450 pathway, possibly by EETs.

8,11,14-Eicosatrienoic Acid↗
PubMed1997

Tyrosine kinase, phosphatidylinositol 3-kinase, and protein kinase C regulate insulin-stimulated NaCl absorption in the thick ascending limb.

We have previously shown a direct stimulatory effect of insulin on NaCl absorption in the medullary thick ascending limb of Henle's loop (mTAL). To further investigate the signal transduction involved, we determined whether tyrosine kinase, phosphatidylinositol 3-kinase (PI3-kinase), and/or protein kinase C (PKC) regulate insulin-stimulated NaCl absorption in the mTAL by in vitro microperfusion methods. In control experiments, insulin increased transepithelial voltage (V(te)) and net lumen-to-bath Cl- flux (J(Cl)). Genistein and methyl 2,5-dihydroxycinnamate, two specific tyrosine kinase inhibitors, abolished the effects of insulin. Wortmannin, a specific PI3-kinase inhibitor, inhibited the action of insulin. The effects of insulin also were inhibited by staurosporin and calphostin C, which are dissimilar inhibitors of PKC. These results indicate that insulin stimulates NaCl absorption in the mTAL through tyrosine kinase, PI3-kinase, and PKC-mediated mechanisms. Moreover, because we have reported previously that insulin causes no detectable change in cytosolic free Ca2+ in the mTAL cells, the present results also suggest that insulin-induced PKC activation is not related to inositol 1,4,5-triphosphate (IP3) production.

Absorption↗
PubMed1997

Impaired vasopressin suppression and enhanced atrial natriuretic hormone release following an acute water load in primary aldosteronism.

The release of arginine vasopressin (AVP) and atrial natriuretic hormone (ANH) and their involvement in renal water and electrolyte metabolism in primary aldosteronism in humans were studied. An oral acute water load (20 ml/kg body weight) was given to each of 12 patients before and after surgical removal of their aldosterone-producing adenoma(s). Plasma AVP and ANH were measured simultaneously, and renal water and electrolyte metabolism and tubular functions were determined. The same water load was given to seven normal subjects and the same parameters were determined. In the presence of mineralocorticoid excess before the operation, plasma AVP was relatively low compared with plasma osmolality (Posm), but was not suppressed in response to decreases in Posm after the water load. Baseline plasma ANH was high and increased further after the water load; urinary dilution and diuresis both remained normal. After the operation, baseline plasma AVP was normal and decreased in response to the decrease in Posm after the water load, with normal urinary dilution and diuresis. Baseline plasma ANH was normal, and did not increase after the water load. The ratio of urinary K and Na clearances and distal tubular reabsorption of Na increased before the operation. These results suggest that there are perturbations of AVP and ANH release in primary aldosteronism, despite the normal urinary dilution after a water load.

Adenoma↗
PubMed1997

Three cases of Gitelman's syndrome possibly caused by different mutations in the thiazide-sensitive Na-Cl cotransporter.

Three adult Japanese cases of Gitelman's syndrome were characterized by secondary aldosteronism, hypokalemic alkalosis, hypomagnesemia, and hypocalciuria. Two were revealed to be familial cases. A mutation in the thiazide-sensitive Na-Cl cotransporter gene, which had already been confirmed in one family (Takeuchi et al. J Clin Endocrinol Metab 81: 4496,1996), was not detected in the other two cases. These observations may possibly support the previous report (Simon et al. Nature Genet 12: 24, 1996) that Gitelman's syndrome is caused by a variety of mutations in the thiazide-sensitive Na-Cl cotransporter.

Aged↗
PubMed1997

Function of angiotensin II type 2 receptor in the postglomerular efferent arteriole.

The balance of vasucular tone between afferent (Af-Art) and efferent arterioles (Ef-Art) is a critical determinant of the glomerular hemodynamics. We recently reported that selective activation of angiotensin II type 2 receptor (AT-2R) causes dilation in the Af-Art. However, the functional role of AT-2R in the Ef-Art has not been defined. In the present study, we microperfused rabbit Ef-Art in vitro, and examined the effect of angiotensin II (Ang II; 10(-11) to 10(-8) M) on the luminal diameter in the presence or absence of an AT-2R antagonist PD123319 (PD; 10(-7) M). Angiotensin II caused dose-dependent constriction in Ef-Arts, with a significant constriction occurring at 10(-11) M; at 10(-10) M the diameter decreased by 28 +/- 4% (N = 6). Pretreatment with PD significantly (P < 0.0125) augmented vasoconstrictor action of Ang II; at 10(-10) M the diameter decreased by 44 +/- 4% (N = 6). We then examined whether blockade of Ang II type 1 receptor (AT-1R) uncovers vasodilator action of Ang II mediated by AT-2R. Efferent arterioles were preconstricted by about 40% with norepinephrine and AT-1R was blocked with its selective antagonist CV11974 (CV; 10(-8) M). Angiotensin II added to preconstricted and CV-pretreated Ef-Arts caused a dose-dependent dilation; at 10(-8) M diameter increased by 28 +/- 3% (N = 5). The dilation was completely abolished by simultaneous pretreatment with PD (N = 4). Our results demonstrate that in the Ef-Art selective activation of AT-2R causes vasodilation, which opposes the vasoconstrictor action of Ang II.

Angiotensin II↗
PubMed1996

20-HETE requires increased vascular tone to constrict rabbit afferent arterioles.

Renal production of 20-hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P-450-dependent arachidonate metabolite, increases during development of hypertension in spontaneously hypertensive rats, and inhibition of its production prevents hypertension. Since 20-HETE is a potent vasoconstrictor, these findings suggest that 20-HETE may contribute to the development of hypertension by elevating renal vascular resistance. In this study we examined the direct action of 20-HETE on the afferent arteriole, a vascular segment crucial to the control of renal vascular resistance. Rabbit afferent arterioles were microperfused at 60 mm Hg in vitro, and 20-HETE was added to the lumen. Although 20-HETE (10(-10) to 10(-6) mol/L) had no effect on the diameter of non-treated afferent arterioles (n=6), it caused dose-dependent constriction when vascular tone was increased with norepinephrine (0.3 micromol/L); 20-HETE at 10(-6) mol/L decreased diameter by 43 +/- 4% (n=6, P < .001). This constriction was abolished by disrupting the endothelium (n=5). Moreover, pretreatment with the cyclooxygenase inhibitor indomethacin (50 micromol/L) or the thromboxane/endoperoxide receptor antagonist SQ29548 (1 micromol/L) significantly (P < .03) attenuated 20-HETE-induced constriction: 20-HETE at 10(-6) mol/L constricted norepinephrine-treated afferent arterioles by 28 +/- 3% (n=6) and 25 +/- 4% (n=5), respectively. These results demonstrate that an increase in afferent arteriolar tone is required for the vasoconstrictor action of 20-HETE, which is partly mediated by the endothelial cyclooxygenase pathway. THus, increased production of 20-HETE in the kidney and increase in afferent arteriolar tone, both of which often precede the development of hypertension, may synergistically contribute to the development of hypertension by elevating renal vascular resistance.

Animals↗
PubMed1996

Bilateral aldosterone-producing adenomas in two patients diagnosed by immunohistochemical analysis of steroidogenic enzymes.

Bilateral adrenal aldosterone-producing adenomas (APA) are rare. It is important to distinguish bilateral APA from idiopathic hyperaldosteronism (IHA) which is due to bilateral hyperplasia of the adrenal cortex. We present two patients with bilateral APA in whom the diagnosis was made histochemically by analyzing steroidogenic enzymes. They showed hypokalemia, high plasma aldosterone concentration (PAC) and suppressed plasma renin activity (PRA). Bilateral adrenal tumors were represented by computed tomography, and surgical resection was performed. In both cases, cytochrome P-450 and other enzymes that were involved in aldosterone synthesis were found mainly in tumor, but little in the zona glomerulosa of the adjacent adrenals, which showed paradoxical hyperplasia. Such cases are difficult to distinguish from IHA. The two disorders were differentiated by immunohistochemical analysis of steroidogenic enzymes.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Therapeutic advantages of angiotensin converting enzyme inhibitors in chronic renal disease.

More than other drugs, angiotension converting enzyme (ACE) inhibitors have been shown to provide better control of glomerular hypertension and improved preservation of renal function. Long-term treatment with captopril slows the progression of renal impairment in diabetic nephropathy; however, the data are inconclusive for non-diabetic nephropathies. ACE inhibitors such as captopril, enalapril, alacepril delapril cilazapril, and lisinopril were equally effective in reducing blood pressure in multicenter clinical trials focusing on renal hypertension in Japan. We studied the influence of ambulatory blood pressure (ABP) and the effects of hypertension therapy in 104 patients with chronic renal glomerulonephritis as diagnosed by renal biopsy. Patients were subdivided into hypertensive, normotensive and hypotensive groups according to ABP and ages. Hypotensive subjects showed an improvement, while normotensive subjects showed a slower rate of progression of renal function loss than hypertensive patients. This suggests that the adequate ABP levels were 100 to 125/55 to 75 in those who were less than 40 years old, 100 to 135/60 to 80 mm Hg in patients aged 40 to 60, and 105 to 140/60 to 85 mm Hg in those over 60 years old. The renal protective effects of calcium antagonists and ACE inhibitors were associated with a reduction in blood pressure, but not with the hypotensive action.

Adult↗
PubMed1996

Diverse effects of calcium antagonists on glomerular hemodynamics.

This study examined the direct effects of calcium antagonists on glomerular hemodynamics. Rabbit afferent (Af-) or efferent arterioles (Ef-Arts) were microperfused in vitro at constant pressure. Ef-Arts were perfused from the distal end of Af-Art through the glomerulus. Increasing doses (10(-10) to 10(-7) M) of nifedipine (Nif), nicardipine (Nic) or manidipine (Man) were added into the lumen of Af- or Ef-Arts preconstricted (by about 40%) with norepinephrine. Although Nif and Nic dilated Af-Arts in a dose-dependent manner, they did not cause any dilation in Ef-Arts. In contrast, Man dilated both Af- and Ef-Arts in a dose dependent manner; Man at 10(-7) M dilated Af- and Ef-Arts by 71 +/- 12% (N = 7) and 38 +/- 3% (N = 6), respectively. Although Man's dilator effect on Ef-Art was not affected by inhibiting nitric oxide (NO) synthesis (N = 6), it was markedly attenuated by eliminating the influence of glomerulus (14 +/- 3% by Man at 10(-7) M, N = 5). These results demonstrate that in addition to dilating Af-Art, Man, but not Nif or Nic, dilates Ef-Art through a glomerulus-derived vasodilator(s) other than NO. Such diverse actions should be taken into consideration when calcium antagonists are used in the treatment of patients with cardiovascular and renal diseases.

Animals↗
PubMed1995

Chemistry and antimicrobial activity of caryoynencins analogs.

Caryoynencins (1) are antibiotics isolated from liquid cultures of a plant pathogen, Pseudomonas caryophylli, and are unstable C18 carboxylic acids with a conjugated dienetetrayne structure. Enyne analogs of caryoynencins were synthesized from monosilylated 1,3-butadiyne 2 (n = 2), 1,3,5-hexatriyne 2 (n = 3), and 1,3,5,7-octatetrayne 2 (n = 4) by alkynyl metal addition to 2,4-hexadienal (3) followed by allylic rearrangement and deprotection. Tetraynol 5 (n = 4) thus obtained was resolved by enzyme reactions. The conjugated dienetetrayne compounds are mixtures of 3E,5E- and 3E,5Z-isomers, which equilibrate by room light. 13C-NMR chemical shifts of polyynes obey simple rules, which can be used for signal assignments. Antimicrobial activities of conjugated enynes and related compounds were examined. The tetrayne analog 6 (n = 4) possesses potent antibacterial and antifungal activities, while triyne and diyne analogs 6 (n = 3 and 2) are less active. Chirality does not affect the activities. An isomeric enyne compound, 2,4-tetradecadiene-7,9,11,13-tetrayn-6-ol (8), showed potent activity against Tricophyton.

Alkynes↗
PubMed1995

Normal sympathetic vasomotor and cardiac parasympathetic activities in patients with primary aldosteronism: assessment by spectral analysis.

The role of the autonomic nervous system in hypertension due to mineralocorticoid excess remains unclear. To address this issue, we performed power spectral analysis of blood pressure (BP) and RR interval oscillations in 20 patients with primary aldosteronism (PA), 54 patients with essential hypertension (EH) and 45 normotensive (NT) subjects. Blood pressure and the degree of organ damage were similar between PA and EH groups. Age did not differ between the three groups. The Mayer wave power spectrum (MWP) of BP (approx. 0.1 Hz), an index of sympathetic vasomotor tone, was smaller in patients with PA than in patients with EH either while subjects were supine (systolic/diastolic; 3.9 +/- 3.2 (SD)/1.5 +/- 1.3 vs. 5.5 +/- 4.2/2.1 +/- 1.6 mmHg2, P < 0.05 for both) or standing (7.6 +/- 6.6/3.0 +/- 3.0 vs. 17.7 +/- 23.7/7.2 +/- 8.3 mmHg2, P < 0.05 for both). Supine respiratory-related power spectrum (RRP) of the RR interval (approx. 0.25 Hz), an index of cardiac parasympathetic tone, was greater in patients with PA than in patients with EH (545 +/- 574 vs. 302 +/- 464 ms2, P < 0.01). The MWP of BP and the RRP of the RR interval were similar between patients with PA and NT subjects. Adrenalectomy reduced the 24-h mean BP (-18 mmHg for systolic BP, P < 0.001; -12 mmHg for diastolic BP, P < 0.01) and increased the 24-h mean heart rate (+8 bpm, P < 0.001). Furthermore, the diastolic MWP increased mildly (+32%, P < 0.05) and the RRP of the RR interval decreased dramatically (-75%, P < 0.01) following adrenalectomy. These results suggest that both vascular sympathetic and cardiac parasympathetic regulatory systems have minor roles in the maintenance of hypertension in patients with PA. The autonomic nervous system contributes more to the maintenance of BP following than prior to adrenalectomy. This information may be useful for the management of hypertension still persists after removal of adrenal adenoma.

Adenoma↗