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Biomedical subjects

M Shichiri

Publications and source records attributed to M Shichiri.

At least 181 records · Page 10Linked to original sources

Appearance of beta-human atrial natriuretic peptide in collagen disease.

To elucidate the circulating forms of human atrial natriuretic peptide (hANP) in collagen disease, we analysed plasma samples obtained from 21 patients with systemic lupus erythematosus, rheumatoid arthritis or progressive systemic sclerosis with no clinical evidence of cardiac involvement. The findings were compared with those obtained from 21 healthy control subjects. Plasma hANP-like immunoreactivity was normal in all but three of the controls and in two patients with the nephrotic syndrome due to lupus nephritis. Reverse-phase high-performance liquid chromatography, gel permeation chromatography and subsequent radioimmunoassay for hANP revealed that the circulating hANP consisted of alpha-hANP, beta-hANP and gamma-hANP in the patients with collagen disease whereas alpha-hANP predominated in the control group. beta-hANP appeared in 18 of the 21 patients but was not observed in the controls. These data suggest that beta-hANP circulates in the plasma of patients with collagen disease even when no myocardial involvement is apparent and that the appearance of beta-hANP is not always associated with an increase in total plasma hANP-like immunoreactivity. Thus the appearance of beta-hANP in plasma is not a phenomenon specific to congestive heart failure.

Adult↗

An artificial endocrine pancreas--problems awaiting solution for long-term clinical applications of a glucose sensor.

The artificial endocrine pancreas is a feedback controlled system regulating insulin delivery on a minute-by-minute basis according to measured blood glucose levels. The bedside-type artificial endocrine pancreas has been proven to be useful not only as a therapeutic tool for diabetic patients but also as an elegant research tool for investigating the pathophysiology of the disease. Recently, a wearable-type, closed-loop system has been developed, of which the breakthrough was the establishment of a needle-type glucose sensor. However, for the long-term clinical use of needle-type glucose sensors, several obstacles remain to be solved, such as oxygen dependency, biocompatibility of the membrane, etc. The most promising method for the non-invasive determination of blood glucose is infrared spectroscopy. The trend in the development of a closed-loop glycemic control system which enables perfectly physiological glycemic regulation on a long-term basis is directed to an implantable device. Much research is being conducted to realize such devices.

Alginates↗

[Development of wearable artificial endocrine pancreas--problems awaiting solutions for long-term clinical application].

By applying artificial endocrine pancreas, the perfect glycemic normalization could be achieved in diabetic patients. The major obstacle for long-term clinical application of artificial endocrine pancreas, however, is the shortage of the life-time of glucose sensor. Thus, it is crucial to develop continuous glucose sensing system with long-life. To augment the biocompatibility, most intensive investigations should be necessary on membrane design for indwelling glucose biosensor. Microdialysis sampling method could also be applied for extracorporeal measurement of subcutaneous tissue glucose concentrations. As an alternative way of long-term glycemic monitoring, the possibility of non-invasive method of glucose measurement by analyzing the infra-red absorption spectra through attenuated total reflection prism was indicated. In conclusion, as a future implantable artificial endocrine pancreas, the combined system of an implantable computer-insulin delivery device and an indwelling glucose biosensor or an optical glucose sensor with telemetric maneuver will be most feasible.

Humans↗

Cytokine-induced release of endothelin-1 from porcine renal epithelial cell line.

To elucidate the mechanism by which endothelin-1 (ET-1) is released from renal epithelial cells, we have investigated the effects of several compounds on release of ET-1-like immunoreactivity (LI) from LLCPK1 cell line. Thrombin, transforming growth factor-beta, cytokines (tumor necrotizing factor-alpha, interleukin-1 beta), and phorbol ester stimulated ET-1-LI release in a time- and dose-dependent manner. The cytokine-induced ET-1-LI release was not affected by indomethacin. Northern blot analysis using cDNA for porcine preproET-1 as a probe revealed a single major band corresponding to the size of ET-1 mRNA in LLCPK1. These data indicate that the preproET-1 gene is also expressed in renal epithelial cells and the release of ET-1 from renal cells is regulated by the similar mechanism to that from endothelial cells.

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↗

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↗

Plasma endothelin levels in hypertension and chronic renal failure.

Endothelin-1 is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-1, plasma levels of immunoreactive endothelin-1 were measured in 32 research subjects with normal renal function (21 normal subjects and 11 patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-1 levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-1 levels than normal subjects (2.29 +/- 1.09 vs. 1.41 +/- 0.50 pg/ml, p less than 0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n = 17) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 7) (3.08 +/- 3.43 vs. 0.73 +/- 0.34 pg/ml, p less than 0.05), and the hemodialyzed hypertensive group (n = 18) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 33) (2.66 +/- 1.92 vs. 1.35 +/- 0.73 pg/ml, p less than 0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-1 levels. These data suggest that circulating endothelin-1 may be partly involved in the development or maintenance of hypertension in humans.

Endothelins↗

Circulating forms of human atrial natriuretic peptide in patients with congestive heart failure.

To elucidate the circulating forms of human atrial natriuretic peptide (hANP) in patients with congestive heart failure (CHF), plasma samples obtained from 36 patients with CHF were analyzed and compared with those from normal subjects. Plasma concentrations of hANP-like immunoreactivity (LI) from normal subjects and patients with mild CHF (class I), as classified by the New York Heart Association (NYHA) functional criteria, did not differ (15 +/- 1 vs. 16 +/- 1 pmol/L, mean +/- SE), whereas plasma levels of hANP-LI in patients with moderate and severe CHF significantly (P less than 0.01) increased in relation to the severity of CHF (class II, 44 +/- 4 pmol/L; class III, 116 +/- 24 pmol/L; class IV, 141 +/- 21 pmol/L). Reverse-phase HPLC and gel permeation chromatography coupled with RIA for hANP revealed that the circulating forms of hANP-LI consisted of alpha-hANP, beta-hANP, and gamma-hANP in CHF, whereas alpha-hANP predominated in normal plasma. The percentage of beta-hANP in total hANP-LI as calculated from the chromatograms by gel filtration was greater in severe CHF (NYHA class III and IV) than those in mild CHF (NYHA class I and II), and apparently exceeded those of other forms. Successful medical treatment for CHF resulted in a marked reduction of total plasma hANP-LI levels with a concomitant disappearance or reduction of beta-hANP in 14 patients examined. These data suggest that beta-hANP and gamma-hANP are secreted from the failing human heart, possibly resulting from the augmented synthesis and/or the altered processing of hANP precursor in cardiocytes, and that circulating beta-hANP may serve as a potential marker for the severity of CHF in man.

Adult↗

Effect of endothelin-1 on release of arginine-vasopressin from perifused rat hypothalamus.

Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide with potent pressor activity. We studied the effect of ET-1 on release of arginine-vasopressin (AVP) from perifused rat hypothalamus. ET-1 (10(-10) to 10(-8) M) significantly stimulated AVP release. The ET-1-induced AVP release was completely blocked in the presence of nicardipine. Our results suggest a possible involvement of ET in the regulation of AVP release.

Animals↗

Secretion of endothelin and related peptides from renal epithelial cell lines.

Using specific radioimmunoassays (RIAs) for endothelin (ET) and big ET, we have studied whether ET and related peptides are secreted from renal epithelial cell lines (LLCPK1 and MDCK) of non-endothelial origin. Dilution curves of extracts of conditioned media from both LLCPK1 and MDCK cell lines were parallel to those of standard porcine (p) ET and big pET in each RIA. Both cell lines incubated in serum-free medium secreted ET- and C-terminal fragment (CTF)-like immunoreactivity (LI) of big ET as a function of time. Reverse-phase HPLC coupled with both RIAs of the extracted media from both cell lines revealed a single component with ET-LI coeluting with pET(1-21) and several components with CTF-LI, one corresponding to the elution position of big pET(1-39), one to its CTF(22-39), and the others eluting earlier than CTF. These data indicate that endothelin and related peptides are synthesized by and secreted from cells other than endothelial cells.

Animals↗

Concomitant secretion of big endothelin and its C-terminal fragment from human and bovine endothelial cells.

A specific radioimmunoassay (RIA) for the carboxyl-terminal fragment (CTF) of big porcine endothelin (pET), an intermediate form of pET, was established to characterize big ET-like and its CTF-like immunoreactivity (LI) secreted from cultured bovine and human endothelial cells (EC). The antibody used crossreacted equally with big pET(1-39) and its CTF(22-39), but not with pET(1-21). Serial dilution curves of the culture media from bovine and human EC were parallel to that of standard CTF. Reverse-phase HPLC coupled with RIAs for big ET and ET of the culture media from bovine and human EC revealed essentially the same elution profiles: two major CTF-LI components, one corresponding to big pET(1-39) and the other to its CTF(22-39), in addition to one major ET-LI component corresponding to pET(1-21). The amounts of CTF-LI were almost equal to that of ET-LI on a molar basis. These data suggest that big ET is processed by a putative ET converting enzyme to yield its CTF and the mature ET(1-21) in EC.

Amino Acid Sequence↗