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Biomedical subjects

A Masuda

Publications and source records attributed to A Masuda.

At least 253 records · Page 14Linked to original sources

A sensitive method for differential determination of kininase I, II and neutral endopeptidase (NEP) in human urine.

In order to clarify the significance of NEP in human renal kallikrein-kinin system, an assay system was developed for the simultaneous determination of kininase I, II and NEP activities in human. Each kininase activity was determined by measuring the hydrolysis of bradykinin in the presence of specific inhibitors of kininase I (2-mercaptomethyl-3-guanidinoethylthiopropanoic acid), kininase II (captopril) and NEP (phosphoramidon) in 8 normal subjects. The effects of the different assay buffers on kininase activities were also investigated by using a phosphate buffer. Total kininase, kininase I, II and NEP activities were 499 +/- 65 ng/min/ml (mean +/- S.E.), 55 +/- 8, 141 +/- 21 and 299 +/- 42, respectively in our method using a tris buffer, while a phosphate buffer brought about activities of 358 +/- 43, 45 +/- 5, 156 +/- 21 and 135 +/- 25 ng/min/ml. The relative contributions of kininase I, II and NEP to total kininase activity were 11, 29 and 59% in our assay system, while they were 13, 44 and 35% when a phosphate buffer was used. From these results it was suggested that 1) phosphate may inhibit urinary NEP activity, so that a tris buffer should be used as the incubation buffer, 2) NEP is the major component of human urinary kininases, and 3) NEP may play an important role in the renal kallikrein-kinin system.

Buffers↗

Localization of neutral endopeptidase in the kidney determined by the stop-flow method.

Recently, the existence of neutral endopeptidase (NEP) as a new kininase in the kidney has been reported. In this study, the localization of NEP in the nephron was investigated and compared with other components of the renal kallikrein-kinin (K-K) system by using a stop-flow method in dog kidneys. The stop-flow method was performed according to the procedures previously reported by Scicli et al and Malvin et al. Five mongrel dogs (weighing 15-20 kg) were used in this study. Kininase I, II and NEP were measured by the modified procedure of Ura et al. Kallikrein and kinin were found in the distal tubules, and kininase I and II were observed in both the distal and proximal tubules. NEP was localized mainly in the proximal tubules. A small peak was also recognized in the distal tubules. From these results, it was suggested that, not only kininase I and II but also NEP existing in the proximal tubules may destroy kinin filtered from the glomeruli, and these kininases existing in the distal tubules may play an important role in connection with kinin producing enzymes on the regulation of activity in the renal kallikrein-kinin system.

Animals↗

Heart rate response to breath-holding during supramaximal exercise.

The cardiovascular responses to breath-holding (BH) during short-lasting supramaximal exercise (415 W) on a cycle ergometer were investigated in 15 healthy male subjects. The arterial oxygen saturation, heart rate (HR), endtidal PO2 and PCO2 were continuously monitored. Firstly, 15 subjects performed exercise during BH, preceded by air breathing (air-BH test), and secondly, exercise without BH. Then 9 of the subjects performed the same procedure as in the air-BH test, except that all subjects breathed 100% O2 for 1 min before apnoea (O2-BH test). In 2 of these subjects, the systemic arterial blood pressure was continuously measured via a catheter in the radial artery and plasma catecholamine concentration [CA] was also measured both during the air-BH and the O2-BH tests. In the later period of the air-BH test, the high HR level became progressively depressed. This response, however, was absent in the O2-BH test. There was a late increase in the arterial blood pressure in both tests, and both tests produced hypercapnia. Only the air-BH test resulted in hypoxia, substantial hypertension and HR-depression. The increase in plasma CA was similar in both tests. The marked HR-depression demonstrated here is ascribed mainly to activation of the peripheral arterial chemoreceptors by asphyxia, and partially to baroreceptor activity due to elevated blood pressure.

Adolescent↗

Effects of ingestion of glucose on GH and TSH secretion: evidence for stimulation of somatostatin release from the hypothalamus by acute hyperglycemia in normal man and its impairment in acromegalic patients.

Ingestion of glucose is known to induce suppression of GH secretion in normal subjects and this phenomenon is often absent in acromegalic patients. To clarify the mechanism of GH suppression in acute hyperglycemia in normal subjects and disturbed GH response in acromegalic patients, the effects of acute hyperglycemia on plasma GH and TSH levels were examined in normal subjects and acromegalic patients. Plasma GH levels were significantly lowered 45-60 min after ingestion of 75 g glucose and elevated at 210 and 240 min in nine normal subjects. Plasma TSH levels were also significantly lowered between 45 and 120 min after ingestion; levels then gradually rose. Subcutaneous administration of 50 micrograms SMS 201-995, a long acting somatostatin analog, lowered plasma TSH levels in both normal subjects and acromegalic patients, and there was no significant difference in the degree of decrease in plasma TSH levels between the normal subjects and patients. These results, taken together with several reports that somatostatin suppresses TSH secretion as well as GH secretion, suggest that acute hyperglycemia stimulates somatostatin release from the hypothalamus, thus causing inhibition of GH and TSH secretion. However, in ten acromegalic patients, only two showed suppression of plasma GH levels to below 50% of basal level and the degree of suppression of TSH secretion was significantly less than in normal subjects in the glucose tolerance test. It is, therefore, suggested that somatostatin release in response to acute hyperglycemia is impaired in most acromegalic patients and that this abnormality may be one of causes for the absence of the normal GH response to acute hyperglycemia in this disorder.

Acromegaly↗

Immunohistochemical study of low affinity Fc receptor for IgE in reactive and neoplastic follicles.

The distribution of low affinity IgE Fc receptors (FceR2, FceRII) in reactive and neoplastic follicles was studied by an indirect immunoperoxidase method with monoclonal antibody specifically reacting to FceRII (H107). The tissues examined in this study included lymph nodes, extranodal tissues of divergent diseases, and follicular lymphomas. In the germinal centers (GCs) of the lymph follicles. FceRII showed a lace-like pattern irrespective of the distribution of IgE. In general, FceRII was positive only in the light zone and not in the dark zone of GCs. The distribution of FceRII was different from that of DRC1(+) FDC which were FceRII(+) and FceRII(-). FceRII was seen by immunoelectron microscopy on the cell surface of follicular dendritic cells (FDCs). IgE-positive GCs in Kimura's disease and Warthin's tumor were intensely positive for FceRII in their entire portion. In IgE-positive GCs, an increased number of FceRII-positive lymphoid GC cells was recognized by immunoelectron microscopic observation. In follicular lymphoma, there were also two types of FDC which were FceRII(+) and FceRII(-). These findings indicated that FceRII on FDCs was closely related to the IgE immune response and also was a marker for functional phase or differentiation of FDCs.

Angiolymphoid Hyperplasia with Eosinophilia↗

Long-term feeding study of N,N'-diphenyl-p-phenylenediamine in F344 rats.

Groups of 50 F344 rats of each sex were fed a diet containing 0.5 or 2% of N,N'-diphenyl-p-phenylenediamine (DPPD) for 104 weeks and were killed 8 weeks after the cessation of DPPD administration. DPPD-treated rats of both sexes showed a dose-dependent reduction in body weight gain, but no lower survival rate, when compared with untreated control rats. Blood and urine analysis showed no remarkable changes due to the treatment. Calcium deposition in the kidney of males was the only significant histological change relating to the treatment. Tumors were found in many organs of all groups, but a significant increase of tumor induction in DPPD-treated groups was not observed.

Administration, Oral↗

Effects of halothane on membrane ionic currents in guinea pig atrial and ventricular myocytes.

We studied the effects of halothane on membrane potentials and ionic currents in single guinea pig atrial and ventricular cells prepared by an enzymatic dispersion procedure. In both atrial and ventricular cells, action potential overshoot and its plateau phase were significantly decreased by halothane (2%) without change in resting potential. However, the duration of the ventricular action potential measured at 90% repolarization was markedly shortened by halothane (2%) (to 60% of control), whereas that of the atrial action potential did not change significantly. Corresponding voltage clamp experiments demonstrated that in atrial cells halothane (2%) significantly depresses the time- and voltage-dependent outward K+ current (IK) (to 46% of control); and that in ventricular cells IK is then nearly absent. In both atrial and ventricular cells halothane had no effect on the inwardly rectifying K+ current (IK1). On the other hand, halothane (2%) decreased the slow inward Ca2+ current (ICa) in both atrial and ventricular cells (to 36% and 29% of control, respectively). The results suggest that the shortened action potential in ventricular cells by halothane may well be responsible for the decrease of the plateau phase resulting from the depression of ICa; and that in atrial cells the depression of IK and ICa by halothane had no significant effect on the duration of action potential.

Action Potentials↗

The influence of halothane and thiopental on respiratory-related nerve activities in decerebrate cats.

The effects of halothane and thiopental on the respiratory efferent activities in the phrenic, recurrent laryngeal and hypoglossal nerves were studied in decerebrate, paralyzed and artificially ventilated cats. Inhalation of halothane (2%, 90 s) and intravenous injection of thiopental (2-3 mg/kg) produced a similar change in the breathing pattern, characterized by an increase in respiratory frequency and a decrease in the respiratory burst discharge in the three nerves studied. Depression of the respiratory activity was greatest in the hypoglossal nerve, intermediate in the recurrent laryngeal nerve, and least in the phrenic nerve. Both drugs diminished the whole power spectral densities of the three nerves. Thiopental selectively attenuated the high frequency peaks of these spectra and shifted the peak frequencies to lower values. Bilateral section of the vagus and carotid sinus nerves had no effect on the action of thiopental on the respiratory neural activities, whereas it decreased, but did not eliminate, the action of halothane. The present results demonstrate that both halothane and thiopental produce a selective depression of the upper airway motor activities, with stronger effects on the hypoglossal nerve. Effects on the peripheral receptors and the central respiratory drives differ between the two drugs.

Administration, Inhalation↗

Pathological observations in HTLV-I associated myelopathy.

The following are the clinical and autopsy findings in a 63-year-old woman with myelopathy associated with the human T-cell lymphotropic virus Type I (HTLV-I). HTLV-I antibody was positive in both the serum and cerebrospinal fluid (CSF). In the lower thoracic region, demyelination and the loss of axons were accompanied by a proliferation of astrocytes, and gliosis was found in the lateral columns. Perivascular and parenchymal infiltrations of macrophages, lymphocytes, and plasma cells were also observed, but neither viral inclusion bodies nor atypical lymphocytes were found.

Axons↗

Detection of the 43,000-molecular-weight glycoprotein in sera of patients with paracoccidioidomycosis.

The 43,000-molecular-weight (43K) soluble glycoprotein was detected in sera of patients with paracoccidioidomycosis by the immunoblot technique by using as the probe rabbit monospecific antisera to this fraction. The 43K antigen was present before treatment in sera of patients with the acute (juvenile) form; it started to disappear from circulation after 10 months of chemotherapy, and it was undetectable after 2 years of treatment. In the chronic cases, the 43K antigen was detected in patients without treatment, and it was absent in the healed cases. The detection of the 43K protein specific to Paracoccidioides brasiliensis may be important for its diagnostic value as well as for modulation of the host immune response.

Antigens, Fungal↗

Mechanisms of suppression of renal kallikrein activity in low renin essential hypertension and renoparenchymal hypertension.

The mechanism of suppression of renal kallikrein activity in low renin essential hypertensive and renoparenchymal hypertensive patients was investigated in this study. From Sephadex G-200 column chromatography studies, a single kallikrein peak was observed in both kallikrein radioimmunoassay and kininogenase activity in all samples from normal subjects, low renin essential hypertensive and renoparenchymal hypertensive patients, and in purified kallikrein solution. The enzyme-specific activity around the kallikrein peak in all urine samples from each group was significantly lower than that in purified kallikrein, and a significantly lower specific activity was found in both patient groups than was found in normal subjects. Moreover, it was also recognized that the specific activity of kallikrein decreased in all cases with the increase of the molecular weight of kallikrein, and this tendency was observed more obviously in the low renin essential hypertensive and renoparenchymal hypertensive patients than in the normal subjects. These results suggest the presence of a kallikrein-specific inhibitor with a low molecular weight in human urine, although the possibility of a variant form of kallikrein cannot be excluded.

Female↗

The somatostatin analog octreotide inhibits the secretion of growth hormone (GH)-releasing hormone, thyrotropin, and GH in man.

The effects of the somatostatin analog octreotide on plasma GH, TSH, and immunoreactive GH-releasing hormone (IR-GHRH) were studied in 10 normal men. After morning sc administration of 50 or 100 micrograms octreotide or placebo, plasma GH, TSH and GHRH were measured frequently for 6 h. Plasma GH or IR-GHRH concentrations did not change after placebo injection, but plasma TSH levels gradually decreased, in conformity with a circadian rhythm during the morning. The mean plasma GH levels after sc injection of 50 or 100 micrograms octreotide declined, and no spontaneous GH pulses occurred for 5 h. Plasma TSH decreased rapidly after both doses of octreotide and was significantly lower than the level after placebo treatment from 90-315 min (P less than 0.05) and 60-360 min (P less than 0.05 or P less than 0.01), respectively. Plasma IR-GHRH levels also were significantly lower from 30-360 min (P less than 0.05) in the group given 100 micrograms octreotide compared with the value in the placebo group. We conclude that octreotide inhibits not only GH and TSH secretion from the pituitary, but also GHRH release from the hypothalamus and/or peripheral tissues. These findings suggest that somatostatin controls GH secretion not only by suppressing pituitary secretion of GH but also by suppressing GHRH release from the hypothalamus.

Adult↗

Circulatory and respiratory responses to lower body negative pressure in man.

Circulatory and ventilatory responses to lower body negative pressure (LBNP) were simultaneously investigated in 8 healthy men before, during, and after the application of -20, -40, and -60 mmHg pressure. Minute ventilation (VE) decreased during LBNP due to a fall in respiratory frequency with sustained tidal volume. The cardiac output (Q) was reduced in proportion to the applied LBNP exposure, while VE decreased to almost the same level at all LBNP applications. In spite of decreased VE, end-tidal PO2 and PCO2 were increased and decreased, respectively, indicating a relative alveolar hyperventilation. The ventilation equivalent for O2 (VE/VO2) increased, while the cardiac output equivalent for O2 (Q/VO2) decreased. The relation between VE/VO2 and Q/VO2 showed a significant negative correlation (r = -0.93, p less than 0.01). The veno-arterial CO2 concentration difference (CvCO2--CaCO2) increased with LBNP, due to a fall in CaCO2 with constant CvCO2. The constant CvCO2 indicated a constant tissue acid-base balance. These observations suggest the existence of a ventilatory mechanism improving the efficiency of respiration in order to compensate for the sustained LBNP depression of Q at a given gas exchange.

Adult↗

IBL-like T cell lymphoma expressing monoclonal gammopathy (macroglobulinemia) in the serum.

A case of IBL-like T cell lymphoma with serum monoclonal gammopathy was reported. A 58-year-old woman, who had suffered from heart failure, was admitted because of asthma attack, fever and lymphadenopathy. Leucopenia with a small amount of atypical lymphocytes was detected. Serum analysis showed monoclonal elevation of IgM-kappa (M-protein) and hyperviscosity. Urinary Bence-Jones protein was detected. Lymph node biopsy revealed the disappearance of normal structure and proliferation of T cells with pale cells which characterized IBL-like T cell lymphoma. Immunocytochemistry revealed the pale cells to bear T cell markers (MT-1, CD 5, CD 8 or CD 4) and IgM-positive cell distribution. Tonsilar biopsy showed the infiltration of atypical lymphoids and pale cells. Bone marrow biopsy showed moderate lymphoplasmacytoid proliferation with lymph follicles. Clinical data and serum analysis suggested macroglobulinemia. Additional lymph node biopsy was performed and revealed IBL-like T cell lymphoma. IBL-like T cell lymphoma is characterized by polyclonal hypergammaglobulinemia. The present case probably occurred initially as IBL-like T cell lymphoma and lymphoplasmacytoid cell proliferation might have followed due to an excess of CD 4+ cells.

Bone Marrow↗

Characterization of an 125I-labeled thromboxane A2/prostaglandin H2 receptor agonist.

Stable synthetic mimetics of thromboxane (TX) A2 and prostaglandin (PG) H2 have been synthesized and reported to stimulate platelets and vascular smooth muscle. The synthetic agonists induce aggregation of isolated platelets and contraction of vascular tissue. The tritiated agonists [3H]U46619 and [3H]U44069 have been used in radioligand binding studies to characterize platelet and vascular smooth muscle TXA2/PGH2 receptors, but have limited usefulness due to their low specific activities and variable specific binding. In an attempt to overcome these problems, we have synthesized a stable, high affinity, 125I-radiolabeled TXA2/PGH2 receptor agonist, [1S-(1 alpha, 2 beta (5Z), 3 alpha(1E,3S*), 4 alpha)]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo - [2.2.1]heptan-2-yl]-5-heptenoic acid (I-BOP). I-BOP induced shape change, increased intracellular free calcium concentrations and aggregated isolated human platelets (EC50 = 0.21 +/- 0.05 nM, n = 3; 4.1 +/- 1.1 nM, n = 4; 10.8 +/- 3 nM, n = 9, respectively). The kinetically determined Kd was 1.02 +/- 0.33 nM (kobs = 0.19 +/- 0.05 min-1, k-1 = 0.097 +/- 0.02 min-1, k1 = 0.119 +/- 0.03 min-1 M, n = 4). Equilibrium binding studies of [125I]BOP to isolated human platelets indicated one class of high affinity sites, Kd = 2.2 +/- 0.3 nM and a maximum binding of 0.028 +/- 0.002 x 10(-12) mol/10(7) platelets (1699 +/- 162 sites/platelet, n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

[The effects of nicardipine on morphological changes and calcium accumulation during ischemic hypoxia in pyramidal nerve cells in the rat cerebral cortex].

The morphological changes and the calcium accumulation were studied in the rat pyramidal nerve cells which had undergone 5% oxygen inhalation and bilateral carotid artery clamping for 15 minutes, using combined methods of electron and the X-ray microanalytical microscopes. To study the protective effects of nicardipine on brain hypoxia, the same techniques were also used after the inhalation. In the 5% oxygen inhalation group, the chromatin clamping in the nucleus was observed, but calcium ions could not be detected in the neuron using the X-ray microanalytical techniques. In the carotid clamping groups under 5% oxygen inhalation, severe nuclear change and mitochondrial swelling were observed and calcium ions were detected in the mitochondrion. After administrations of nicardipine under 5% oxygen inhalation and under carotid clamping with 5% oxygen, similar morphological changes were recognized by the electron microscope as compared to the non-administration groups. The rate of calcium ion detection was not different significantly (P less than 0.05) between the nicardipine administration and the non-administration groups. It is, therefore, concluded that notable protective effects of nicardipine on ischemic hypoxia were not recognized in this experiment.

Animals↗

[The experimental study on long-term cardiac preservation: the efficacy of low-flow continuous perfusion with fluorocarbon].

We compared the effect of simple immersion and continuous perfusion on long-term cardiac preservation, and evaluated the effectiveness of perfusion with oxygenated fluorocarbon solution. The isolated rabbit hearts were preserved for 24 hours at 4 degrees C using the following five preservation techniques: (1) simple immersion with Collins M solution (Group I), (2) perfusion with oxygenated Collins M solution at a flow rate of 10 ml/hr (Group II), (3) perfusion with the same solution as in Group II at a flow rate of 20 ml/hr (Group III), (4) perfusion with oxygenated Collins M solution containing 10% fluorocarbon at a flow rate of 10 ml/hr (Group IV), (5) perfusion with the same solution as in Group IV at a flow rate of 20 ml/hr (Group V). The hearts of Group I showed a significant decrease of myocardial ATP and an increase of myocardial lactate during preservation compared to the hearts of perfusion groups. Assessment of isovolumic left ventricular function following 24-hour preservation using a support animal showed a significant decrease of Max dp/dt and increase of end-diastolic pressure in the hearts of Group I. Perfusion with fluorocarbon (Group IV and V) significantly increased oxygen consumption compared to Group II and III in association with minimum accumulation of myocardial lactate, indicating that aerobic metabolism during preservation is better maintained in the fluorocarbon-perfused hearts. Moreover, CPK release and myocardial water gain during preservation were significantly less, and left ventricular function following preservation was significantly better in these hearts. Increasing the flow rate from 10 ml/hr to 20 ml/hr resulted in sustained increase in perfusion pressure (1.80 +/- 0.53 to 3.70 +/- 0.34 mmHg) and myocardial water content (79.2 +/- 0.4 to 87.2 +/- 0.3%) during preservation in the hearts of Group III, but it did not further improve left ventricular function despite significant enhancement of myocardial oxygen uptake in both Group III and V. These results suggest that hypothermic low-flow continuous perfusion with oxygenated Collins M solution is superior to simple immersion with the same solution for long-term cardiac preservation, and that the addition of fluorocarbon to the perfusate enhances the efficacy of such a perfusion.

Animals↗