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Biomedical subjects

Y Matsuda

Publications and source records attributed to Y Matsuda.

At least 505 records · Page 28Linked to original sources

Effects of ANP receptor antagonists on ANP secretion from adult rat cultured atrial myocytes.

Atrial natriuretic peptide (ANP) is a hormone-secreted predominantly by atrial myocytes. ANP exerts many of its actions via activation of the particulate guanylyl cyclase receptor ANPR-A and the formation of guanosine 3',5'-cyclic monophosphate (cGMP), which serves as a second messenger in the target cells. Using membrane-permeable cGMP analogues (8-bromo-cGMP and dibutyryl- cGMP), we first tested the hypothesis that ANP secretion by adult rat cultured atrial myocytes can be modulated through the second messenger cGMP. Second, we examined the effects of two competitive ANPR-A receptor antagonists, namely HS-142-1 and anantin, on cGMP formation and ANP secretion from cultured atrial myocytes. Cultured atrial myocytes secreted large quantities of immunoreactive (ir) ANP under basal conditions. We found that cGMP analogues inhibited basal irANP secretion from cultured atrial myocytes, whereas HS-142-1 and anantin had stimulating effects. HS-142-1 and anantin reduced cGMP formation in cultured atrial myocytes at basal conditions. These results suggest an autoregulatory mechanism of ANP secretion by atrial myocytes in an autocrine/paracrine fashion.

Animals↗

Cerebral magnetic resonance angiographic findings in severe preeclampsia.

OBJECTIVE: The purpose of our study was to investigate the cerebral pathophysiology of severe preeclampsia using the noninvasive method of magnetic resonance angiography. STUDY DESIGN: We studied cerebral magnetic resonance angiography findings in 9 severely preeclamptic patients. RESULTS: Magnetic resonance angiographies were abnormal on first scanning within 48 h postpartum, followed by normal findings on repeat scanning during the 1st postpartum month in 6 patients. The most common abnormality was vascular narrowing of anterior cerebral artery and basilar artery. Three of these 6 patients complained of headaches and/or visual disturbances. CONCLUSION: This study shows that cerebral artery vasospasm is seen in some severe preeclamptic patients.

Adult↗

Relationship between granulocyte elastase levels and perinatal infections.

This study was conducted in order to investigate the usefulness of granulocyte elastase levels as predictive factors in the onset of perinatal infections. The subjects were 41 patients who delivered within 48 h after amniocentesis after giving their informed consent. The relationship between cervical granulocyte elastase (Cx-E), serum C-reactive protein (CRP) and amniotic fluid granulocyte elastase (Af-E), and placental infections and neonatal infections was comparatively investigated. In some cases, gastric juice granulocyte elastase in neonates (Gj-E) was measured, and the correlation by site was investigated. Elastase levels were not used as a management protocol. In predicting neonatal infections, diagnostic efficacy (sensitivity x specificity) of placental infections (0.97) and abnormal Af-E (0.79) were superior to those of abnormal Cx-E (0.40) and abnormal CRP (0.49). There was no correlation between Cx-E and Af-E or between Cx-E and Gj-E; however, a very close correlation was noted between Af-E and Gj-E. In predicting abnormal amniotic fluids, Cx-E (> or = 1.2 micrograms/ml) + CRP (> or = 1.0 mg/dl) had the highest diagnostic efficacy with 0.58. These findings demonstrate that Af-E is a good index for predicting the onset of neonatal infections. In predicting abnormal amniotic fluid, it might be advisable to consider amniocentesis in order to diagnose intrauterine infections, when both Cx-E and CRP show abnormal levels.

Amniocentesis↗

Increased mitogenic response to heparin-binding epidermal growth factor-like growth factor in vascular smooth muscle cells of diabetic rats.

We investigated the mitogenic effects of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in vascular smooth muscle cells (SMCs) obtained from rats with streptozotocin (STZ)-induced diabetes and evaluated the role of heparan sulfate proteoglycan (HSPG) in inducing these effects. HB-EGF significantly increased DNA synthesis in the SMCs of diabetic rats (STZ-SMCs) compared with control rats (control SMCs). However, the mitogenic effects of EGF, which shares EGF receptors with HB-EGF, and basic fibroblast growth factor, another heparin-binding growth factor, were similar in STZ-SMCs and control SMCs. The mitogenic response to HB-EGF in SMCs of insulin-treated diabetic rats was similar to the response in control SMCs. HB-EGF-induced autophosphorylation of EGF receptors was increased in STZ-SMCs compared with control SMCs, although the number of EGF receptors in STZ-SMCs was 40% of that in controls. This increased mitogenic response to HB-EGF in STZ-SMCs was completely inhibited by treatment with heparitinase, chlorate, and a synthetic peptide corresponding to the heparin-binding domain of HB-EGF. Compared with heparan sulfate isolated from control SMCs, heparan sulfate isolated from STZ-SMCs was of smaller molecular size and caused a greater mitogenic effect of HB-EGF. These findings suggest that the mitogenic response to HB-EGF is increased in SMCs of diabetic rats. Changes in cell-associated heparan sulfate in STZ-SMCs may be related to the increased mitogenic response to HB-EGF.

Animals↗

A functional role for endogenous atrial natriuretic peptide in a canine model of early left ventricular dysfunction.

Asymptomatic or early left ventricular dysfunction in humans is characterized by increases in circulating atrial natriuretic peptide (ANP) without activation of the renin-angiotensin-aldosterone system (RAAS). We previously reported a canine model of early left ventricular dysfunction (ELVD) produced by rapid ventricular pacing and characterized by an identical neurohumoral profile and maintenance of the natriuretic response to volume expansion (VE). To test the hypothesis that elevated endogenous ANP suppresses the RAAS and maintains sodium excretion in ELVD, we assessed the effects of antagonism of ANP on cardiorenal and neurohumoral function in ELVD. Chronic ANP suppression was produced by bilateral atrial appendectomies before the production of ELVD by rapid ventricular pacing (ELVD-APPX, n = 5). This group was compared with a separate group with ELVD and intact atrial appendages (ELVD-INTACT, n = 8). ELVD-APPX was characterized by lower circulating ANP (50 +/- 11 vs. 158 +/- 37 pg/ml, P < 0.05), activation of plasma renin activity (PRA) (9.4 +/- 2.4 vs. 0.6 +/- 0.4 ng/ml per h, P < 0.05) and aldosterone (36.4 +/- 12.5 vs. 2.5 +/- 0.0 ng/dl, P < 0.05) when compared to ELVD-INTACT. In comparison to the ELVD-INTACT group, sodium excretion was decreased before and during VE in the ELVD-APPX group. Acute ANP antagonism was produced by administration of the particulate guanylate cyclase coupled natriuretic peptide receptor antagonist, HS-142-1, to seven conscious dogs with ELVD and intact atrial appendages (ELVD-INTACT). HS-142-1 decreased plasma concentrations and renal generation of the ANP second messenger, cGMP, and was associated with activation of PRA and sodium retention with enhanced tubular sodium reabsorption. These data support a significant role for elevated endogenous ANP in the maintenance of sodium excretion and regulation of the RAAS in experimental ELVD.

Aldosterone↗

Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine fetus: effects of a non-peptide antagonist for atrial natriuretic peptide receptor.

Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natriuresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 +/- 7 to 234 +/- 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 +/- 0.7 versus 34.6 +/- 2.3% and 0.7 +/- 0.1 versus 2.6 +/- 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 +/- 94 versus 497 +/- 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 +/- 0.03 to 0.70 +/- 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 +/- 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 +/- 0.13 to 0.25 +/- 0.06 and 1.30 +/- 0.66 +/- 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 +/- 5 to 9 +/- 2 and 83 +/- 16 to 39 +/- 5 mumol/min). GFR decreased after HS (3.0 +/- 0.8 to 2.4 +/- 0.5 and 3.6 +/- 0.3 to 2.6 +/- 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 +/- 2.7 to 2.7 +/- 0.5 and 16.1 +/- 2.4 to 11 +/- 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 +/- 37 to 436 +/- 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.

Anemia↗

Distribution of the Kexin family proteases in pancreatic islets: PACE4C is specifically expressed in B cells of pancreatic islets.

The distribution of Kexin family proteases in adult rat pancreatic islets was investigated by immunohistochemical means using a series of specific antibodies specific for PC1, PC2, PC6, Furin, PACE4A and a recently identified member of the Kexin family, PACE4C. PACE4C expression was limited to B cells of the pancreatic islets. PC2 was found in A and in some D cells more than in B cells and PC1 was evident only in B cells. Furin and PC6 were weakly and evenly expressed in the entire islet. PACE4A was hardly found in the islets. These findings indicated that individual Kexin family proteases are uniquely distributed in the islets and suggested that these proteases share roles in these cells as follows: PC2 is involved in the peptide hormone precursor processing in A cells and in D cells, and PACE4C, PC1 and PC2 (mainly PACE4C and PC1) are responsible for the processing event(s) specific to B cells.

Animals↗

[Participation of sialic acid residue in the fibrinogen-fibrin conversion by thrombin].

In order to estimate the effects of sialic acid residues in fibrinogen on the fibrinogen-fibrin conversion by bovine thrombin the Michaelis constant (Km) and maximum velocity (Vmax) were determined. The Km value obtained by the use of intact-fibrinogen was smaller than that of asialo-fibrinogen. This fact suggests that the sialic acid residues affected the formation of the enzyme-substrate complex. It was also found that in comparison with the asialo-fibrinogen, the intact-fibrinogen was significantly influenced in the gel formation time by the ionic strength in the reaction solution.

Animals↗

PS-990, a novel microbial metabolite, reversibly induces neurite extension in neuroblastoma cells.

PS-990, which is a novel microbial metabolite, induced neurite formation in a murine neuroblastoma cell line, Neuro2A. In the presence of PS-990 at 30 micrograms/ml, significant neurite outgrowth was observed. Cultures maintained for 12 h in the presence of PS-990 resulted in the maximal number of neurite-bearing cells, and then the neurites formed were gradually retracted. The retracted cells again yielded the neurite formation when the cells were exposed again to PS-990. PS-990 inhibited both the cell growth and thymidine incorporation into the cells at the same concentration range. Although the type of neurite formation with PS-990 is similar to that with a cyclic AMP analog and indeed PS-990 has an inhibitory potency against calcium and calmodulin-dependent cyclic nucleotide phosphodiesterase, the intracellular cyclic AMP level was not elevated when treated with PS-990. These results suggest that PS-990 reversibly induces neurite formation with arrest of the cell growth through a mechanism distinct from an increase in the intracellular cyclic AMP concentration.

3',5'-Cyclic-AMP Phosphodiesterases↗

Isolation of myosin light chain kinase inhibitors from microorganisms: dehydroaltenusin, altenusin, atrovenetinone, and cyclooctasulfur.

Dehydroaltenusin, cyclooctasulfur, atrovenetinone, and altenusin were isolated from the culture broths of Penicillium verruculosum IAM-13756, Streptomyces verticillus subsp. tskushiensis ATCC-21633, Penicillium sp. SPC-16375, and Penicillium sp. SPC-16524, respectively, as new myosin light chain kinase (MLCK) inhibitors. These compounds inhibited the calmodulin-dependent activity of MLCK with IC50 values of 0.69, 0.86, 3.7, and 350 microM, respectively. Among them, dehydroaltenusin was the best MLCK inhibitor in terms of potency and selectivity examined in the purified enzyme systems.

Benzopyrans↗

Magnetic resonance imaging of the central nervous system in the kitten.

The optimum technical conditions for magnetic resonance imaging (MRI) of the central nervous system (CNS) in the 3-week-old kitten were investigated with a low (0.2 T) magnetic field MRI unit equipped with a custom-made solenoid radio frequency (RF) coil. In the brain, T1 weighted images (TR/TE = 500/38 msec) and T2 weighted images (TR/TE = 1,800/110 msec) clearly delineated each anatomical portion of the brain. In the spinal cord, T2 weighted images (TR/TE = 1,500/110 msec) demonstrated structures distinctly. These results suggest that even low magnetic field MRI can be used for noninvasive scanning of small animals including new born animals.

Animals↗

Prevalence of upper respiratory tract disorders detected with a flexible videoendoscope in thoroughbred racehorses.

A total of 350 thoroughbred racehorses found clinically as having coughs or abnormal breath sounds underwent endoscopic examination of the upper respiratory tract at rest. As a result, abnormal endoscopic findings were obtained in all horses, demonstrating that thoroughbred racehorses with a clinical abnormality in the respiratory system necessarily had disorders in the upper respiratory tract. Whereas 11 types of disorder were observed, a combination of three different types of disorder were found in the highest frequencies in 3-, 4- and 5-year-old horses (27.8%, 29.2% and 29.7%, respectively). Among 6-year-olds or older horses, those having only one type of disorder accounted for the greatest proportion (47.6%). The prevalence of pharyngeal lymphoid hyperplasia or abnormalities of the epiglottis decreased with age.

Animals↗

[Intestinal motility after massive small bowel resection].

To evaluate intestinal motility after 80% massive distal small bowel resection (MSBR), we continuously monitored interdigestive and postprandial bowel motility using bipolar electrodes and/or contractile strain gage force transducers in conscious beagle dogs before, and at 0-4 weeks and 8-13 months after the surgery. Fasting duodenal migrating myoelectric (or motor) complexes (MMCs) occurred at longer intervals in the short-term after 80% MSBR than in controls, and were simulated in long-term that in controls. MMCs arising from the duodenum were often migrated to the proximal jejunum, the jejunum above the anastomosis, and to the terminal ileum beyond the anastomosis. The velocity of duodenal MMC propagation was slowed in every intestinal segment in the short-term, and had not recovered even long after the operation. The duration of the postprandial period without duodenal MMCs was prolonged significantly in the short-term, and still remained longer in the long-term than in controls. These findings suggest that changes in gut motility after MSBR tend to compensate for the shorter intestine and maintain small bowel absorption early postoperatively, and adaptations of motility would occur over the long-term to increased intestinal absorption.

Animals↗

Non-insulin-dependent diabetes mellitus complicated with idiopathic hypoparathyroidism.

We report a case of non-insulin-dependent diabetes mellitus (NIDDM) complicated with idiopathic hypoparathyroidism. A 74-year-old male was hospitalized because of diplopia. He was revealed to have NIDDM. The levels of serum Ca and intact-PTH were 6.3 mg/dl and < 5 pg/ml, respectively. Brain computed tomography revealed abnormal calcification in the cerebral basal ganglia and the cerebellum. After recovery from hypocalcemia, the endogenous insulin secretion was normalized. It is suggested that the pathogenesis of NIDDM in this patient may have been related to an insulin secretory defect as a result of hypocalcemia in addition to the hereditary risk.

Aged↗

Surgical removal of pineal region meningioma--three case reports.

Three patients with large or huge meningiomas of the pineal region presented with headache, vomiting, gait and visual disturbance, apraxia, agnosia, and transient amnestic aphasia. Computed tomographic scans revealed round, high-density areas of 8 x 7 x 7 cm, 5 x 5 x 4 cm, and 3 x 3 x 3 cm in the pineal region. Angiography revealed that the bilateral internal cerebral veins and the great vein of Galen were stretched and significantly displaced upward in one patient, and downwards in the other two. The meningiomas appeared to originate from the verum interpositum and falcotentorial junction, respectively. The tumors were removed subtotally or totally via an occipital interhemispheric transtentorial approach and/or infratentorial supracerebellar approach. The postoperative courses were uneventful, and no neurological deficit was detected postoperatively. Pineal region tumors with a maximum diameter of 5 cm or larger should be operated on via a unilateral or bilateral occipital interhemispheric transtentorial approach, regardless of the angiographic findings, because this permits a wide operative field and can be followed, if necessary, by an infratentorial supracerebellar approach. Selection of the operative approach for a relatively small pineal region tumor should depend on the angiographic findings: downward displacement of the bilateral internal cerebral veins and the great vein of Galen indicates an occipital interhemispheric transtentorial approach, whereas upward displacement indicates an infratentorial supracerebellar approach.

Adult↗

RES-701-2, -3 and -4, novel and selective endothelin type B receptor antagonists produced by Streptomyces sp. I. Taxonomy of producing strains, fermentation, isolation, and biochemical properties.

RES-701-2, -3 and -4, novel cyclic peptide endothelin antagonists, were isolated from the culture broths of Streptomyces sp. RE-701 and RE-896, RES-701s selectively inhibited the ET-1 binding to endothelin type B receptor (ETB receptor) with IC50 values ranging from 5 to 20 nM. Taxonomy of the producing strains, fermentation, isolation and biochemical properties of RES-701s are described.

Amino Acid Sequence↗

RES-1214-1 and -2, novel non-peptidic endothelin type A receptor antagonists produced by Pestalotiopsis sp.

RES-1214-1 and -2, novel and non-peptidic endothelin antagonists, were isolated from the cultured broth of a fungus, Pestalotiopsis sp. RE-1214. RES-1214-1 and -2 selectivity inhibited the ET-1 binding to endothelin type A receptor (ETA receptor) with IC50 values of 1.5 microM and 10 microM, respectively. RES-1214-1 and -2 inhibited the increase in intracellular Ca2+ concentration elicited by 1 nM ET-1 in A10 cells. Taxonomy of producing strains, fermentation, isolation, structural determination, and biochemical properties of RES-1214-1 and-2 are described.

Animals↗