Advances in enzymatically coupled field effect transistors.
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Biosensing Techniques↗
Biomedical subjects
S Shiono
Publications and source records attributed to S Shiono.
Data processing for multi-channel optical recording: action potential detection by neural network.
Using a neural network, we have developed a program for fast and precise detection of action potentials (AP) in raw multi-channel optical recording data. The AP detection was performed in two steps: first, peaks were detected in raw optical data, and, second, the peaks were classified by the neural network into APs, noise and undecided peaks. The network was optimized and trained by the backpropagation learning algorithm, employing some thousands of manually classified peaks. The performance of the optimized network was found to be not completely satisfactory, although it was better than the classification by template matching and nearest-neighbor rules. The addition of a signal-to-noise ratio (SNR) of a peak to the network classification improved the classification performance: in comparison with the manual classification results, 96% of manually classified APs were detected. The causes of classification errors were discussed. In spite of the fact that the program required a slight amount of human intervention for undecided peaks, the program could allow mostly automatic AP detection.
Action Potentials↗
448-detector optical recording system: development and application to Aplysia gill-withdrawal reflex.
The spatial resolution of a fast, multichannel, optical recording apparatus has been improved in an attempt to increase the completeness of optical recordings of neuron activity responsible for the Aplysia gill-withdrawal reflex. We developed a new optical apparatus, increasing the number of pixels to 448. Action potential activity from 168 to 192 neurons could be detected. Hence, the number of optically detected neurons increased about 2.5 times in comparison with a previously used 100- or 124-detector optical apparatus. Because optically detected action potential signals were shown to be due to the cell body of a neuron, it was possible to know its position as well as its approximate size. The distribution of the detected active neurons and those neurons that showed an apparent change in spike frequency to the siphon stimulation were determined.
Action Potentials↗
Post-translational processing and secretory pathway of human atriopeptin in rat pheochromocytoma cells.
Atriopeptin (AP) is expressed in several tissues with each tissue capable of specific differences in processing of the prohormone (pro-AP) to mature low molecular forms of the peptide. Since pro-AP has low biological activity, processing into mature AP is a critical activation event. This observation prompted us to study whether granule storage or regulated secretion of AP is essential for cleavage of mature peptide. We examined the processing of AP in adrenal medulla derived cells, using the rat pheochromocytoma cell line (PC12 cell) stably transfected with a genomic human AP DNA in the presence and absence of nerve growth factor (NGF), and also examined the mechanism of AP secretion and compared the results with those obtained using transfected chinese hamster ovary cells (CHO cells). The amount of prohormone was 5-10 fold higher than that of low molecular form of AP in the transfected PC12 cells. This ratio was essentially unchanged in differentiated PC12 cells after NGF treatment of the cells. Potassium depolarization of the transfected PC12 cells caused a 5-fold increase in AP release into the medium primarily as the intact prohormone. On the other hand, transfected CHO cells only exhibited constitutive AP release which is non-response to depolarization. These results suggest that the AP prohormone is sorted into secretory granules as the prohormone in PC12 cells and undergoes regulated release in response to depolarization indicating granule storage or release is not the critical determinant of AP prohormone cleavage.
Adrenal Gland Neoplasms↗
Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in DOCA-salt hypertension. Effects of atrial natriuretic polypeptide monoclonal antibody.
To elucidate the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in hypertension, we investigated the biosynthesis and secretion of ANP in deoxycorticosterone acetate (DOCA)-salt hypertensive rats and also examined the effect of passive immunization with monoclonal antibody raised against alpha-rat ANP on the development of hypertension in DOCA-salt rats. The plasma ANP level in DOCA-salt rats was significantly elevated in comparison to control rats. While the atrial ANP concentration in DOCA-salt rats was not significantly altered, the atrial level of ANPmRNA in DOCA-salt rats was two-fold higher than that in control rats. These results suggest the augmented biosynthesis of ANP in the atrium and the oversecretion of ANP from the heart in DOCA-salt rats. The levels of ANP and ANPmRNA in the ventricle of DOCA-salt rats exhibited significant increases, compared with those in control rats, suggesting the induction of ANP gene expression in the ventricle of DOCA-salt hypertensive rats under pre/after overload. Weekly intravenous administrations of monoclonal antibody with high affinity for alpha-rat ANP significantly augmented the rise in blood pressure of DOCA-salt rats. These results support the hypothesis that the augmented secretion of ANP is one of the defensive mechanisms to counteract high arterial pressure in this model of hypertension.
Animals↗
Isolation and sequence determination of human brain natriuretic peptide in human atrium.
We isolated human brain natriuretic peptide (human BNP) from the human atrium. Sequence analysis has revealed that it is a 32-amino-acid peptide with the sequence S-P-K-M-V-Q-G-S-G-C-F-G-R-K-M-D-R-I-S-S-S-S-G-L-G-C-K-V-L-R-R-H, which is identical to the C-terminal sequence (77-108) of the human BNP precursor deduced from the cDNA sequence. The sequence of human BNP (77-108) is preceded by Pro75-Arg76 in the human BNP precursor, which is the same processing signal as Pro97-Arg98 of the precursor of atrial natriuretic peptide (ANP). The processing of the BNP precursor occurs in the cardiocyte, although that of the ANP precursor in the cardiocyte is unclear at present.
Amino Acid Sequence↗
Alternative mechanisms for atriopeptin prohormone processing by isolated perfused rat hearts.
The isolated perfused rat heart releases atriopeptin-28 [AP28 (ANF99-126)], whereas the storage form of AP in the heart is the intact prohormone AP126 (ANF1-126). Right atrial stretch or phenylephrine (5 x 10(-5) M) stimulated the release of AP28. The processing of the prohormone during stretch was inhibited by infusion of the protease inhibitor aprotinin, resulting in the appearance of intact AP126 in the cardiac effluent. Other protease inhibitors including p-aminobenzamidine and soybean trypsin inhibitor did not alter prohormone processing by the isolated heart subjected to stretch. In contrast, aprotinin did not block the prohormone processing induced by phenylephrine. Ca+(+)-free medium markedly inhibited prohormone processing during stretch without a significant effect on AP release, whereas phenylephrine-stimulated AP release was completely suppressed by Ca+(+)-free medium. Exogenous AP126 could be cleaved by isolated rat hearts perfused either with Krebs-Henseleit solution or with Ca+(+)-free medium. However, amino acid sequence analysis revealed that the prohormone cleavage in Ca+(+)-free medium occurred at sites other than between Arg98 and Ser99 and that the resultant low molecular weight APs were not AP28. These findings suggest: 1) the characteristics of the enzyme(s) involved in the processing of AP prohormone in isolated perfused rat hearts are different from the described properties of purified enzymes; 2) in isolated perfused rat hearts the specific AP processing enzyme is Ca++ dependent, whereas nonspecific cleavage does not necessarily require Ca++ and 3) two independent AP processing pathways differentially activated by mechanical (stretch) and pharmacologic (alpha 1-adrenergic agonist) stimuli exist.
Animals↗
A study on limulus amebocyte lysate (LAL) reactive material derived from dialyzers.
The amebocytes of horseshoe crab (Limulus) hemolymph contain a coagulation system highly sensitive to bacterial endotoxins. Limulus amebocyte lysate (LAL) reactive material derived from cuproammonium rayon membranes, however, is not an endotoxin and acts upon the alternative pathway in the coagulation cascade found in Limulus amebocyte lysate. This study confirmed these facts by using the coagulation system of Limulus without factor G, which is a substrate of the alternative pathway. LAL reactive material lingered in the circulation for a relatively long time. In acute hemodialysis, its plasma concentration increased by an average of 100 pg/ml with each dialysis and eventually reached a plateau of approximately 300 pg/ml. In patients with chronic renal failure under regular hemodialysis, the mean level of LAL reactive material was 330.0 +/- 8.0 pg/ml before hemodialysis which increased by 70.6 +/- 20.7 pg/ml after four hours of hemodialysis.
Acute Kidney Injury↗
Assessment of the early cellular membrane response to live Escherichia coli bacteremia.
Alterations in skeletal muscle cellular function during septic shock have been previously demonstrated. However, whether these alterations represent a specific response to the septic state or are simply a consequence of low flow is uncertain. The present study was designed to evaluate the cellular membrane response to the early bacteremic state, prior to the onset of hemodynamic compromise. A clinically relevant model of sepsis was achieved in six mongrel dogs by intraarterial infusion of live Escherichia coli organisms and concurrent volume loading with lactated Ringer's solution. Four sham-treated dogs served as controls. Forty-eight hours after induction of sepsis, resting transmembrane potential (Em) was measured in a hindlimb adductor muscle. Contemporaneous muscle biopsy was performed for determination of transmembrane water and electrolyte distribution. The bacteremic state was associated with depolarization of Em to -79.7 +/- 1.2 mV from a basal value of -89.3 +/- 0.2 mV (P less than 0.01), while Em in the sham-treated group remained unchanged over the same time course. In addition, there was a significant increase in the calculated intracellular Na+ and Cl- concentrations in the septic group (P less than 0.02), while intracellular K+ was unchanged. These data are consistent with a selective increase in cell membrane permeability to Na+ and indicate that cellular alterations in skeletal muscle occur early in the septic course, in the absence of hemodynamic compromise. This alteration in membrane permeability appears to be common to cells of disparate organ systems in response to sepsis, and may represent a protean manifestation of cellular injury.
Adenosine Triphosphate↗
Adrenergic mechanisms contribute to alterations in regional perfusion during normotensive E. coli bacteremia.
The complex role of adrenergic mechanisms in the pathogenesis of sepsis and shock remains incompletely understood. Recent reports have suggested that adrenergic mechanisms may play an important modulatory role in arachidonate metabolism during early sepsis, specifically in the synthesis of the vasoactive metabolites thromboxane A2 and prostacyclin. The purpose of the present set of experiments was to evaluate the extent to which adrenergic mechanisms contribute to early alterations in regional perfusion during Gram-negative bacteremia, using the mixed alpha adrenergic receptor antagonist phenoxybenzamine hydrochloride. Male Sprague-Dawley rats received a 3-hour continuous intraarterial infusion of either saline (n = 7) or 6.6 +/- 0.4 x 10(8) live E. coli colony forming units (n = 7), after which regional perfusion was determined using 51Cr-labelled microspheres (16.5 +/- 0.1 micron). Significant reductions (p less than 0.05) in blood flows to the renal, gastric, cecal, pancreatic, and splenic beds, as well as a reduction (p less than 0.05) in the calculated portal venous flow, were observed in the bacteremic group while mean arterial blood pressure remained unchanged. Further experiments conducted in 14 rats with preexisting alpha adrenergic receptor blockade revealed relative preservation of renal, gastric, cecal, and portal venous blood flows during bacteremia. These data identify alterations in regional perfusion during early E. coli bacteremia occurring before changes in systemic arterial blood pressure, and indicate that adrenergic mechanisms participate in the modulation of such.
Animals↗
Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats.
To explain the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in the development of hypertension, we examined the effect of chronic, repetitive administrations of MAb raised against alpha-rat ANP in two rat models of hypertension, spontaneously hypertensive rats of the stroke prone substrain (SHR-SP), and deoxycorticosterone acetate (DOCA)-salt rats. Weekly intravenous administrations of MAb with high affinity for alpha-rat ANP, named KY-ANP-II (MAb[KY-ANP-II]), started at the age of 6 wk, significantly augmented the rise in blood pressure of SHR-SP, compared with control SHR-SP treated with another MAb with quite low affinity for alpha-rat ANP, named KY-ANP-I (MAb[KY-ANP-I]), throughout the observation period. The administrations of MAb[KY-ANP-II] had no significant effect on blood pressure of age-matched normotensive Wistar Kyoto rats, compared with those receiving MAb[KY-ANP-I]. Weekly administrations of MAb[KY-ANP-II] also significantly aggravated hypertension in DOCA-salt rats. Blood pressure of DOCA-salt rats treated with MAb[KY-ANP-II] was significantly higher than that of DOCA-salt rats treated with MAb[KY-ANP-I] throughout 8 wk of DOCA and 1% saline administration. The administration of MAb[KY-ANP-II] also significantly attenuated exaggerated diuresis and natriuresis in DOCA-salt rats compared with those treated with MAb[KY-ANP-I]. Elevated plasma cGMP levels of both SHR-SP and DOCA-salt rats were significantly reduced by the administration of MAb[KY-ANP-II]. These results suggest the compensatory role of augmented secretion of ANP in these hypertensive rats and support the concept that augmented secretion of ANP could represent an antihypertensive deterrent mechanism.
Animals↗
Effects of naloxone on vasopressin secretion in conscious rats: evidence for inhibitory role of endogenous opioid peptides in vasopressin secretion.
The effects of naloxone, an opioid antagonist, on arginine vasopressin (AVP) secretion were examined in conscious unrestrained rats under both basal and stimulated conditions. Intravenous injection of naloxone in a dose of 0.1 mg/kg did not significantly affect the basal plasma AVP level. However, 0.5 or 2.5 mg/kg naloxone significantly raised the basal AVP level in euhydrated rats. Naloxone (0.5 mg/kg) significantly enhanced AVP secretion after 72-h water deprivation. However, the enhancement was more prominent in euhydrated rats than in dehydrated rats. Pretreatment with naloxone (0.5 mg/kg) also significantly prolonged AVP secretion induced by intracerebroventricular injection of angiotensin-II (100 ng). Moreover, naloxone (0.5 mg/kg) significantly increased AVP secretion induced by intracerebroventricular injection of carbachol (10 ng). Naloxone (0.5 mg/kg) altered neither basal blood pressure nor the angiotensin-II-induced pressor response, but augmented the carbachol-induced pressor response. This suggests that facilitation of AVP secretion by naloxone is not due to a reflex mechanism resulting from decreased blood pressure. These results indicate that endogenous opioid peptides exert a tonic inhibitory control on AVP secretion in rats.
Angiotensin II↗
[Invasive candidiasis: its predisposing factors, usefulness and limitation of cultural study in its diagnosis, and consideration on the appropriate amphotericin B therapy].
We have reviewed 38 patients with invasive candidiasis and examined its predisposing factors, usefulness and limitation of cultural study in its diagnosis, and effective usage of amphotericin B in its treatment. Invasive candidiasis was diagnosed in 2.4% of the patients admitted during the past 5 years. One of the most important predisposing factors for development of invasive candidiasis was extensive use of antibiotics. Destruction of the mechanical barrier against bacteria and fungi caused by endotracheal intubations and various catheterization was another important factor. Mucosal lesion of the gastrointestinal tract, including stress ulcer, non-specific inflammatory bowel disease and esophageal ulcer, was seen in 30% of the patients. These lesions were thought to be the portal of entry for candida to systemic dissemination. AMPH is the most effective antifungal agent. Total dose of 300 to 1000 mg was effective in the patients. Dosage over 1000 mg was associated with progressive decrease in creatinine clearance. This decrease was irreversible even after discontinuation of AMPH. Candidal overgrowth within the G1 tract was considered to precede invasive candidiasis. Oral AMPH administration was effective in such conditions.
Adult↗
Augmented synthesis of beta-human atrial natriuretic polypeptide in human failing hearts.
To elucidate the synthesis of atrial natriuretic polypeptide (ANP) in the failing heart, eighteen human right auricles obtained at cardiovascular surgery were studied. The concentration of alpha-human ANP-like immunoreactivity (alpha-hANP-LI) in human right auricles ranged from 13.8 to 593.5 micrograms/g, and the tissue alpha-hANP-LI concentration in severe congestive heart failure (CHF) (New York Heart Association (NYHA) functional class III or IV) was much higher than those in mild CHF of NYHA class I and class II. The alpha-hANP-LI in the human auricle consisted of 3 major components of ANP, gamma-human ANP (gamma-hANP), beta-human ANP (beta-hANP) and alpha-human ANP (alpha-hANP). The predominant component of alpha-hANP-LI was gamma-hANP in the mild CHF, whereas beta-hANP and/or alpha-hANP were prevailing in the severe CHF and, especially, beta-hANP was markedly increased in human failing hearts.
Adult↗
Exaggerated secretion of atrial natriuretic polypeptide during dynamic exercise in patients with essential hypertension.
The plasma concentration of atrial natriuretic polypeptide (ANP) was measured in nine patients with essential hypertension during two grades of exercise tests performed in the supine position on a bicycle ergometer. The plasma ANP concentration significantly increased from 97.0 +/- 19.2 pg/ml to 107.6 +/- 23.7 pg/ml (p less than 0.05) during low-grade exercise (50% of the maximal heart rate) and from 96.2 +/- 16.5 pg to 192.8 +/- 30.7 pg/ml (p less than 0.01) during high-grade exercise (75% of the maximal heart rate). During high-grade exercise plasma epinephrine and norepinephrine concentrations showed significant increases. The plasma ANP concentration was significantly correlated with systolic blood pressure (r = 0.51; p less than 0.05). Patients with essential hypertension showed greater absolute increases in the plasma ANP concentration and systolic blood pressure during exercise compared to normotensive subjects. These results suggest that exercise stimulates secretion of ANP in response to its intensity in patients with essential hypertension and that a greater rise in atrial pressure, resulting from a greater elevation of systolic blood pressure, may be involved in the exaggerated secretion of ANP in patients with essential hypertension.
Atrial Natriuretic Factor↗
Potent depressor action of leumorphin, a kappa-opioid agonist, in conscious rats.
To investigate the role of leumorphin, a kappa-opioid agonist derived from proenkephalin B (neoendorphin/dynorphin precursor) in the central cardiovascular control, the effects of intracerebroventricular (ICV) administration of leumorphin on basal blood pressure and angiotensin II (AII)-stimulated pressor response were examined in conscious unrestrained rats. The ICV injection of 0.06 and 0.6 nmol of leumorphin caused a significant decrease in basal blood pressure (delta mean arterial pressure (MAP): -6.5 +/- 2.7 and -7.2 +/- 1.7 mm Hg, respectively). The ICV injection of AII (0.1 nmol) elicited a pressor response (delta MAP: 21.4 +/- 1.1 mm Hg). This pressor response was significantly reduced by the simultaneous administration of leumorphin, and furthermore, the blood pressure was lowered below the basal level. These depressor actions of leumorphin were partially antagonized by the preadministration of naloxone, an opiate antagonist. These results together with our previous works on the potent inhibitory actions of leumorphin on drinking and vasopressin secretion suggest the possible involvement of leumorphin in the central regulation of blood pressure and body fluid homeostasis.
Animals↗
Peptides derived from atrial natriuretic polypeptide precursor in human and monkey brains.
Using radio-immunoassays for the C-terminal sequence of alpha-atrial natriuretic polypeptide [atrial natriuretic factor (ANF)-(99-126)], alpha-ANP (17-28) [ANF-(115-126)], which corresponds to gamma-human ANP [115-126; gamma-hANP-(115-126)] and for the N-terminal sequence of gamma-hANP [human ANF-(1-126)], gamma-hANP-(1-25) [human ANF-(1-25)], we detected the parallel distribution of alpha-hANP-like immunoreactivity and gamma-hANP-(1-25)-like immunoreactivity in the human and monkey brains, with the highest concentrations in the midbrain and the pons. High performance gel permeation chromatography coupled with the two radio-immunoassays and also with another radio-immunoassay using a monoclonal antibody against the N-terminal sequence of alpha-ANP revealed that gamma-ANP is synthesized in the brain and cleaved into N-terminally deleted form(s) of alpha-ANP and 10-K N-terminal fragment(s) of gamma-ANP, which coexist within the neuron. These results suggest that the post-translational processing of gamma-ANP in the brain is different from that in the heart.
Animals↗
Central interaction of the brain atrial natriuretic polypeptide (ANP) system and the brain renin-angiotensin system in ANP secretion from heart--evidence for possible brain-heart axis.
To elucidate the involvement of the brain renin-angiotensin system and the brain atrial natriuretic polypeptide (ANP) system in the regulation of ANP secretion from the heart, the effects of intracerebroventricular administration of angiotensin II and ANP on the plasma ANP level were examined in conscious unrestrained rats. The intracerebroventricular administration of angiotensin II at doses of 100 ng and 1 microgram significantly enhanced ANP secretion induced by volume-loading with 3-mL saline infusion (peak values of the plasma ANP level: control, 220 +/- 57 pg/mL; 100 ng angiotensin II, 1110 +/- 320 pg/mL, p less than 0.01; 1 microgram angiotensin II, 1055 +/- 60 pg/mL, p less than 0.01). The intracerebroventricular injection of angiotensin II at the same doses alone had no significant effect on the basal plasma ANP level. The enhancing effect of central angiotensin II on ANP secretion induced by volume-loading was significantly attenuated by pretreatment with the intravenous administration of the V1-receptor antagonist of vasopressin or with the intracerebroventricular administration of phentolamine. The intracerebroventricular administration of alpha-rANP(4-28) (5 micrograms) had no significant influence on the basal plasma ANP level; however, it significantly attenuated central angiotensin II potentiating effect of volume-loading induced ANP secretion. These results indicate that the brain renin-angiotensin system regulates ANP secretion via the stimulation of vasopressin secretion and (or) via the activation of the central alpha-adrenergic neural pathway, and that the brain ANP system interacts with the brain renin-angiotensin system in the central modulation of ANP secretion from the heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗