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Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 559 records · Page 31Linked to original sources

Receptor binding and vasoconstrictor activity of big endothelin.

We studied the effects of synthetic porcine big endothelin (ET), a putative 39-residue intermediate deduced from cDNA sequence analysis, on receptor binding activity in cultured rat vascular smooth muscle cells as well as its vasoconstrictive activity in rat pulmonary artery. Big ET was about two orders of magnitude less active than ET in the receptor binding and vasoconstriction assays. Our data are consistent with the contention that big ET is an intermediate which can be converted into fully bioactive 21-residue mature ET.

Animals↗

[Usefulness of assessing bone mineral content of cortical bone in patients with lingering imbalance of bone metabolism].

The CT numbers of cortex at the level of 20 cm (CT20) and of spongiosa in the lateral condyle at 2 cm (CT02) proximally from the distal end of the femur, and the bone mineral density of spongiosa in L3 body (BMD), were obtained by QCT. The study included 48 patients with rheumatoid arthritis or chronic renal failure as well as 10 healthy volunteers. The relationships of CT20 vs BMD in the regions above and below a critical value of BMD were quite different from each other. Similar relationships were observed in the plot of CT20 vs CT02. The results indicated that the demineralization of cortex was much less than that of spongiosa while the mineral content of spongiosa kept higher than a critical value, but the demineralization of cortex surpassed that of spongiosa once the mineral content of spongiosa had become lower than the critical value. It is necessary to assess bone mineral content of cortex especially in patients with lingering imbalance of bone metabolism.

Adult↗

Brain natriuretic peptide is cosecreted with atrial natriuretic peptide from porcine cardiocytes.

Using primary cultures of atrial cardiocytes from neonatal pig, the secretion brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP)-like immunoreactivities (LI) was studied in vitro. Porcine cardiocytes time-dependently secreted both BNP-LI and ANP-LI into medium under a serum-free condition, although the amount of BNP-LI secreted was about one-third that of ANP-LI. Phorbol ester and Ca2+ ionophore had less stimulatory effects on secretion of BNP-LI than that of ANP-LI. Reverse-phase HPLC of the conditioned medium revealed a single major BNP-LI component corresponding to synthetic porcine BNP(1-26). These data suggest that a small molecular weight form BNP, possibly BNP(1-26), is cosecreted with ANP from porcine cardiocytes.

Animals↗

Beat-to-beat evaluation of cardiac function during recovery from upright bicycle exercise in patients with coronary artery disease.

The purpose of this study was to evaluate the time course of cardiac function during recovery from upright bicycle exercise in patients with coronary artery disease. Twelve patients with coronary artery disease performed a symptom-limited exercise test on a cycle ergometer. Left ventricular function was continuously monitored during exercise and recovery with a computerized cadmium telluride detector following the intravenous injection of technetium-labeled red blood cells. Although the end-diastolic volume (153.4 +/- 76.1 ml) and end-systolic volume (100.5 +/- 67.3 ml) at the end of exercise were significantly higher than the respective resting values, stroke volume (52.8 +/- 16.1 ml) and ejection fraction (38.0 +/- 12.2%) were not different from the respective resting values. The recovery of cardiac output was relatively slow compared with that of heart rate, because stroke volume rose sharply early in recovery. The rise in stroke volume was chiefly a result of a significant decrease in end-systolic volume between 1 and 4 minutes of recovery. These changes may result from an immediate afterload reduction coupled with a relatively slow decrease in sympathetic stimulation. The time course of cardiac function during recovery from exercise in cardiac patients is substantially different from that of normal subjects and may be a sensitive way to evaluate the peripheral vascular function and deteriorated cardiac function in cardiac patients.

Adult↗

Localization of 90-kDa heat shock protein in the kidney.

Antibody against 90-kDa heat shock protein (HSP 90) was produced in rabbits. The obtained antibody was highly specific to the antigen. Using the antibody, the intrarenal distribution of HSP 90 was studied in frozen sections of normal rat kidneys by fluorescent and enzymic immunohistochemistry. HSP 90 was predominantly present in the region from the distal convoluted tubule to the medullary collecting duct at a high intensity, and in glomerular podocytes and Bowman epithelial cells at a much lower intensity. Other segments of the nephron were stained little, even at a lower dilution of the antibody. Blood vessels and interstitial tissues were not stained. HSP 90 was localized in the cytoplasm and not in the nucleus. Moreover, immunohistochemical staining of HSP 90 showed greater intensity at the luminal side of the cells. These observations suggest that HSP 90 might play important roles in the kidney.

Animals↗

The role of the left ventricle in atrial natriuretic peptide secretion in acute mitral regurgitation.

To examine the role of the ventricle in ANP secretion, the atrial natriuretic peptide (ANP) concentration in the plasma, left atrial tissue and left ventricular tissue were observed in a canine during the course of experimental reversible mitral regurgitation (MR). For reversible MR, a basket catheter was inserted into the left atrium via the pulmonary vein and fixed at the mitral valve. The regurgitation arose when the tip basket wire was extended and disappeared immediately when it was closed. Left atrial pressure (LAP), right atrial pressure (RAP) and pulmonary artery pressure (PAP) increased significantly during MR, and decreased to the normal level after recovery from MR. Plasma ANP concentration showed a reversible change in correlation with LAP and RAP in each canine studied. The ANP level in the atrial and ventricular tissue decreased during MR, and the low levels were maintained after recovery from MR. Both the left arterial and left ventricular tissue ANP levels showed the same changes in acute MR. Therefore, it was suggested that normal ventricles might play a role in ANP secretion in acute MR.

Animals↗

Phosphorylated and dephosphorylated types of non-activated glucocorticoid receptor.

We purified glucocorticoid receptors quickly but very partially using DEAE-resin. [3H]-Triamcinolone acetonide-labeled and non-activated receptors in the quickly purified fraction were found to be separated into two fractions (P-2 and P-3) by hydroxyapatite column chromatography. The P-2 receptor was the main component, and the ratio of P-2/P-3 was around 2. The molecular weights of the two receptors were calculated to be the same, 242,000: Rs = 6.2 nm and s20,w = 9.0. Treatment of the receptor with catalytic subunits of phosphoprotein phosphatase 2A1 reduced the P-2/P-3 ratio from 2 to 0.5, while treatment with catalytic subunits of cAMP-dependent protein kinase and ATP increased it to 2.5. The isolated P-3 receptor could be converted into the P-2 type by the kinase treatment. Tungstate, a phosphatase inhibitor, stabilized the P-2 receptor, and the P-2/P-3 ratio was larger than 3 when the DEAE-fraction was prepared in the presence of tungstate. However, the tungstate effect was not very strong, and the P-2 type tended to change into the P-3. [3H]-Triamcinolone acetonide-labeled and non-activated receptors were purified very highly by using an affinity gel; the procedure required more than 10 h. Only the P-3 form was observed in the preparation of highly purified receptors. Hormone-free receptors were affected by neither the phosphatase nor the kinase. The results indicate that the hormone binding makes the receptor sensitive to phosphatase. The reversibly dephosphorylated receptor is more stable than the non-dephosphorylated one, and can be activated.

Animals↗

The physiological and biological significances of human atrial natriuretic peptide in neonates.

The purpose of our study was to analyze the physiological and biological significances of the high human atrial natriuretic peptide (hANP) levels during early post-natal period. The absolute values or changes of plasma hANP concentrations did not correlate with the absolute values or changes of body weight, blood pressure, urinary sodium/creatinine and urinary aldosterone/creatinine ratios. Gel permeation chromatography of samples from two neonates revealed the presence of two molecular forms of hANP, alpha and beta, both in the plasma and urine. In the plasma, the beta-hANP was predominant on the 3rd day of life and the alpha-hANP on the 6th day of life. The change from one form to another was independent of the absolute value of hANP. We obtained no evidence suggestive of a physiological role of the high plasma hANP concentration during the early post-natal period. However, because of biological differences between these two fractions, their distribution must be taken into account when attempting to interpret the high hANP values observed in neonates.

Atrial Natriuretic Factor↗

Effects of ANF on cGMP synthesis in inner medullary collecting duct subsegments of rats.

The inner medullary collecting duct (IMCD) is thought to be a major target site for atrial natriuretic factor (ANF) action. The IMCD is divided into two subsegments (IMCD1, outer third; and IMCD2,3, inner two-thirds) based on differences in urea and water permeability. IMCD1 has similar characteristics to the outer medullary collecting duct (OMCD). To elucidate whether there are any differences among these segments in ANF actions, we investigated the effects of ANF on guanosine 3',5'-cyclic monophosphate (cGMP) synthesis in IMCD subsegments and the OMCD. We also examined the effects of arginine vasopressin (AVP) on adenosine 3',5'-cyclic monophosphate (cAMP) synthesis. IMCD subsegments (IMCD1,2,3) and OMCD were microdissected; and ANF-stimulated cGMP synthesis and AVP-stimulated cAMP synthesis were measured. cGMP synthesis stimulated by 10(-6) M ANF in IMCD1,2,3 (0.78 +/- 0.15, 0.81 +/- 0.19, 0.62 +/- 0.10 fmol.mm-1 x 3 min-1, mean +/- SE respectively, n = 10-11) was significantly (greater than 20-fold) higher than that in OMCD (0.03 +/- 0.02 fmol.mm-1 x 3 min-1, n = 7), and there was no difference among IMCD subsegments. On the other hand, cAMP synthesis stimulated by 10(-7) M AVP in IMCD subsegments was similar to that in OMCD. We conclude that IMCD is homogenous as a target site of ANF and is clearly distinguished from OMCD. In addition, more than half of ANF-stimulated cGMP synthesis in IMCD are considered to occur in IMCD1, simply because IMCD1 is dominant in population among IMCD subsegments. As target sites of AVP, IMCD subsegments are similar to OMCD.

Animals↗

Cell pH regulation in rabbit outer medullary collecting duct cells: mechanisms of HCO3(-)-independent processes.

To clarify mechanisms of intracellular pH (pHi) regulation in outer stripe of outer medullary collecting duct (OMCDOS), isolated perfused OMCDOS of the rabbit were loaded with 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF), and single cell pHi was monitored by an image processing system. Initial pHi recovery rates (dpHi/dt, pH unit/s x 10(3)) after intracellular acid load made by NH4Cl prepulse were determined. In the absence of exogenous CO2-HCO3-, dpHi/dt was 12.3 +/- 0.9 (means +/- SE) in principal cells (PC), and 11.5 +/- 1.0 in intercalated cells (IC). In PC, total ambient Na+ removal halted pHi recovery (dpHi/dt = 0.6 +/- 0.5), and pHi recovered when Na+ was added to the basolateral (dpHi/dt = 14.7 +/- 0.8) but not to the luminal (dpHi/dt = 0.9 +/- 0.5) solutions. This bath Na+ effect was amiloride inhibitable. In IC, pHi recovered (dpHi/dt = 6.4 +/- 0.3) in the absence of ambient Na+. This pHi recovery was significantly reduced by luminal 0.5 mM N-ethylmaleimide (NEM) or 0.5 mM N,N'-dicyclohexylcarbodiimide (DCCD). Basolateral NEM or DCCD had no significant effect. Basolateral addition of Na+ significantly accelerated the pHi recovery. These data suggest the presence of basolateral Na(+)-H+ exchange in both PC and IC, and luminal NEM- and DCCD-sensitive H+ pump in IC of rabbit OMCDOS.

Animals↗

Effect of azosemide on the in vitro perfused thick ascending limb of Henle's loop from the mouse.

Direct effect of azosemide on the mouse thick ascending limb of Henle's loop was examined by the isolated tubules perfusion technique, and the effect was compared with that of furosemide. Azosemide added to the tubular lumen reversibly suppressed the lumen positive potential (PDt) and decreased the net chloride reabsorption. Dose-response studies of these two drugs suggested that azosemide was about 5 times as potent as furosemide. The more potent effect of azosemide compared with furosemide was confirmed by a paired study in the same tubules. At a concentration of 10(-5) mol/l azosemide suppressed PDt by 91.4%, furosemide by 65.6%.

Animals↗

Diabetic hypouricemia as an indicator of clinical nephropathy.

We studied the possible association of the low serum uric acid level with incipient diabetic nephropathy in non-insulin-dependent diabetes mellitus (NIDDM). Of 201 NIDDM patients without a diminished glomerular filtration rate, 66 patients (32.8%) showed moderate hypouricemia of less than the mean-1 SD of 201 nondiabetic controls. Thirteen (6.5%) showed marked hypouricemia of less than the mean-2 SD. Hypouricemic patients showed normal daily urinary urate excretion with a markedly elevated urate clearance/creatinine clearance ratio. Most were under poor glycemic control, and presented either negative or intermittent clinical proteinuria. However, neither poor glycemic control, nor the presence of proteinuria or retinopathy alone significantly affected the serum uric acid level of the whole diabetic population. The glomerular filtration rate was determined in comparable groups of diabetic patients with hypouricemia and nonhypouricemic diabetic controls. The hypouricemic group showed a significantly higher endogenous creatinine clearance and lower serum beta-2-microglobulin levels than the nonhypouricemic group. These findings suggest that the hypouricemic group had a higher glomerular filtration rate. Long-term observation of up to 12 years of the above patients revealed that, in most patients, persistent hypouricemia was observed prior to the initial appearance of intermittent proteinuria. We hypothesize that glomerular hyperfiltration also occurs in NIDDM and that it lowers the serum uric acid by increasing the renal clearance of urate. Hypouricemia may also predict the future progression of incipient nephropathy in NIDDM.

Blood Glucose↗

Decreased fractional excretion of urate as an indicator of prerenal azotemia.

Although the fractional excretion of uric acid (FEUA) is known to reflect extracellular fluid volume changes, the diagnostic significance of decreased FEUA in dehydration has not been previously reported. We studied the possible association between low FEUA and acute prerenal azotemia, and its diagnostic value, compared with other traditional indices, in discriminating prerenal azotemia from renal parenchymal causes of acute renal failure. In 65 chronic renal disease patients, 174 FEUA measurements were obtained from 24-hour urine collections. FEUA levels increased as reciprocal serum creatinine levels decreased. All 8 patients with prerenal azotemia showed significantly decreased FEUA values compared with chronic renal disease patients with a comparable degree of serum creatinine elevation, whereas all 7 patients with acute renal failure had FEUA values higher than those of chronic renal disease patients with comparable creatinine levels. FEUA values in prerenal azotemia were distinctly lower than those in acute renal failure (p less than 0.001). Patients with prerenal azotemia showed a lower fractional excretion of sodium, a lower fractional excretion of chloride and renal failure index, and a higher urine-to-plasma creatinine ratio than those with acute renal failure (p less than 0.05). However, these traditional indices were not useful in discriminating between the two conditions. The urine-to-plasma urea nitrogen ratio and the ratio of plasma urea nitrogen to creatinine showed no statistical difference between prerenal azotemia and acute renal failure. We conclude that, in acute azotemia, a decreased FEUA value may represent a reliable indicator of prerenal azotemia in the differential diagnosis of acute renal failure.

Acute Kidney Injury↗

Adult Fanconi syndrome secondary to kappa-light chain myeloma: improvement of tubular functions after treatment for myeloma.

A 66-year-old man with kappa-light chain multiple myeloma had adult Fanconi syndrome. Renal tubular transport abnormalities consisted of renal tubular acidosis, renal glycosuria, aminoaciduria, phosphaturia and renal hypouricemia. After therapy for multiple myeloma, urinary Bence Jones protein became undetectable, and all these renal tubular abnormalities except urate wasting were corrected. Histological examination revealed electron-dense tubular and rod-like deposits in proximal tubular epithelium. This clinical observation suggests that the renal tubular transport defects were secondary to the myeloma process, possibly due to Bence Jones proteinuria.

Aged↗

Abnormal accumulation of vanadium in patients on chronic hemodialysis therapy.

Vanadium (V) has been reported to inhibit a number of enzyme activities such as those of Na(+)-K(+)-ATPase. The main excretory pathway of this element is via the kidney. These facts led us to study the V distribution in uremic patients. As a result, hemodialysis patients at our dialysis center exhibited extremely high levels of serum V (23.9 +/- 11.3 ng/ml, n = 43) as compared with healthy adults. Nondialysis patients did not show increased serum V concentrations. The V contents were significantly elevated in the skin and in the aortae of hemodialysis patients. It was found that the tap water from Kanagawa prefecture, Japan, had the highest V concentrations among the 21 cities in Japan and the US. In conclusion, oral ingestion of V-contaminated water has likely caused an accumulation of the metal in patients with end-stage renal failure.

Adult↗

Renal tubular hypouricemia: evidence for defect of both secretion and reabsorption.

Two patients had hypouricemia due to increased uric acid clearance. They showed no decrease of urate clearance to creatinine clearance ratio (Cua/Ccr) following pyrazinamide administration, and no increase of Cua/Ccr after probenecid. One patient showed a limited decline in Cua/Ccr after intravenous furosemide. In the other patient, neither acetylsalicylate nor furosemide produced any noticeable change in Cua/Ccr. Both showed a normal diuretic response after intravenous furosemide. The results indicate that they had massive defects in urate transport along the nephron, probably including both secretion and reabsorption.

Aged↗