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Biomedical subjects

M Kawamura

Publications and source records attributed to M Kawamura.

At least 631 records · Page 35Linked to original sources

Establishment of human osteoblastic cells derived from periosteum in culture.

We isolated osteoblastic cells derived from human periosteum and established them in culture. Their growth depended on the presence of ascorbic acid, and the doubling time was 40 to 60 h. The requirement for ascorbic acid was used to high production of collagen. These cells produced mainly type I collagen and only small amounts of type III collagen determined by reducing sodium dodecyl sulfate SDS-polyacrylamide gel electrophoresis. The total collagen yield was about 10 mg from 2 X 10(7) cells. The cells could be continuously cultured in alpha-minimum essential medium supplemented with 10% fetal bovine serum for 18 to 40 population doubling levels, depending on the age of the donated periosteum. These cells have the ability to calcify when incubated with 2 mM alpha-glycerophosphate-Na2. Calcification as viewed by the naked eye appeared from Day 15 after treatment. Treatment with the active formed vitamin D3, 1, 25 dihydroxyvitamin D3 enhanced calcification significantly and stimulated osteocalcin production. By electron microscopy, cells with many projections on their surfaces showed well-developed rough endoplasmic reticulum and actinlike fibers, and larger numbers of lysosomes, mitochondria, and secretion granules. Many matrix vesicles, in which minerals were initially localized, and well-banded collagen fibrils were seen in the intercellular spaces. These observations demonstrate typical osteoblastic morphology. The above results indicate that cultured cells from human periostem are osteoblastic cells that have the capacity to differentiate into osteocytes and to deposit calcified minerals in response to 1,25 dihydroxyvitamin D3.

Alkaline Phosphatase↗

Pulmonary gas exchange effects by nitroglycerin, dopamine and dobutamine during one-lung ventilation in man.

The effects of nitroglycerin, dopamine and dobutamine on pulmonary gas exchange were determined in 21 adult patients during two-lung and one-lung ventilation. Nitroglycerin, in 1 microgram.kg-1.min-1, decreased cardiac index (CI) and PaO2 during both two- and one-lung ventilation, and increased in Qs/Qt during one-lung ventilation. There were no significant changes in the measured variables during infusion of dopamine, 5 microgram.kg-1.min-1. Dobutamine, 5 microgram.kg-1.min-1, increased CI and PaO2 did not change during two-lung ventilation. During one-lung ventilation, PaO2 increased from (mean value +/- SD) 168 +/- 46 to 201 +/- 52 mmHg (P less than 0.01) with dobutamine infusion. Qs/Qt decreased from 29.2 +/- 7.0 to 26.0 +/- 6.2 per cent (P less than 0.05) without any change in pulmonary vascular resistance index during one-lung ventilation. We conclude that dobutamine has advantages over dopamine and nitroglycerin during one-lung ventilation.

Blood Pressure↗

Assessment of hepatic excretory function in chronic liver disease by hepatobiliary scintigraphy.

Hepatobiliary scintigraphy was performed in 23 normal subjects and 47 patients with chronic liver disease (chronic hepatitis; n = 27, liver cirrhosis; n = 20) to evaluate its availability as a test of liver function. After intravenous administration of Tc-99m N-pyridoxyl-5-methyl-tryptophan, the data were acquired for 60 min and the time-activity curves of ROIs (the heart and liver) were generated. In two compartment model simulation, the early blood clearance rate (kl), late blood clearance rate (km), hepatic uptake rate (ku) hepatic excretion rate (ke), and hepatic excretion T 1/2 were calculated. There was no significant difference in those four k values in normal and chronic hepatitis. However, in liver cirrhosis each of them, except km, was lower than in normal subjects. The kl value correlated closely with the indocyanine green plasma clearance test, whereas the ke and T 1/2 values were closely correlated with the level of serum bilirubins. Only hepatobiliary scintigraphy showed the excretory function of the liver quantitatively and the ke value was helpful in detecting hepatic excretory dysfunction early in chronic liver disease before serum bilirubins increased.

Adolescent↗

A new approach to the detection of DNA damage.

A method is described which permits the detection of damage produced in unlabeled DNA by daunorubicin, nitrogen mustard, or radiation. After exposure to one of the agents the cells are embedded in an agarose block and lysed to release the DNA. The agarose block is then transferred to a well in an agarose gel and electrophoresis performed. DNA damage is recognized by the presence of DNA whose molecular weight is less than the DNA of cells not exposed to the damaging agent. By transferring the DNA to a solid phase the DNA can be probed with radiolabeled cDNAs to assess damage in specific genes. DNA damage detected by this method correlates well with a loss in the clonogenic capacity of the cells. This method will permit assessment of biologically meaningful DNA damage in unlabeled clinical specimens.

DNA↗

Localizing efficiency of [48V]vanadyl-pheophorbide in tumor as a new tumor imaging agent.

[48V]vanadyl-pheophorbide (48V-Pheo) was synthesized by insertion of 48V into pheophorbide (Pheo), a decomposition product from chlorophyll. At 24 h after injection, 48V-Pheo showed a clearer image of an FM3A tumor than inorganic 48V. This agent also accumulated in MH 134 and S 180 tumors as well as in FM3A tumors. The imaging efficiency was dependent on the affinity of Pheo for tumors. 48V-Pheo seems to be suitable as a tumor imaging agent in conjunction with photodynamic therapy.

Animals↗

Radiation-induced oesophageal stricture in a case of Bloom's syndrome.

A case of Bloom's syndrome with lung cancer treated by radiation therapy is described. Squamous cell carcinoma of the lung responded well to a tumour dose of 50.4 Gy. The most serious complication of therapy was an oesophageal stricture induced by only 30.6 Gy to the mediastinum. Brief reviews of radiation-induced oesophageal stricture and radiosensitivity in Bloom's syndrome are presented.

Adult↗

Alterations in cerebrospinal fluid angiotensin II by sodium intake in patients with essential hypertension.

1. Angiotensin (ANG) levels were measured in the cerebrospinal fluid of 15 patients with essential hypertension on a high sodium diet for 1 week and on a low sodium diet for a further week. ANGs were determined using a system of extraction by Sep-Pak cartridges followed by h.p.l.c. combined with radioimmunoassay. 2. Sodium depletion resulted in increases of ANG II in the cerebrospinal fluid from 1.16 +/- 0.38 (SEM) to 1.83 +/- 0.43 fmol/ml (P less than 0.01) and of ANG III from 0.65 +/- 0.11 to 0.86 +/- 0.15 fmol/ml (P less than 0.01). 3. The ANG II level in the cerebrospinal fluid was found to be unchanged and recovery of added ANG II was approximately 90%, even after incubation for 3 h, on both diets. Thus, it is unlikely that ANG II is produced or degraded in the cerebrospinal fluid in vitro. 4. There was no significant correlation between the cerebrospinal fluid and the plasma ANG II concentration on the low sodium diet. 5. These results suggest that the cerebrospinal fluid ANG II level increases with sodium depletion, and that the effect of the level of ANG II on the activity of the angiotensin-forming system in the central nervous system may be assessed by determination of ANG II in the cerebrospinal fluid in patients with essential hypertension.

Adult↗

Identification of des-(Gly-Ile)-endozepine as an effector of corticotropin-dependent adrenal steroidogenesis: stimulation of cholesterol delivery is mediated by the peripheral benzodiazepine receptor.

Delivery of cholesterol to inner mitochondrial membranes is rate-limiting for steroidogenesis in the zona fasciculata of adrenal cortex. A protein that stimulates this process was isolated to homogeneity from bovine adrenal tissue. This protein's primary structure has been determined in its entirety by a combination of automated Edman microsequencing, fast-atom bombardment mass spectrometry (FAB-MS). The sequence was identical to that previously reported for bovine brain endozepine, except that it lacks the last two residues, -Gly-Ile, at the C terminus. To our knowledge, isolation of an endozepine-related protein from a tissue other than brain has not been reported previously. Endozepine competes with benzodiazepines for saturable binding sites in synaptosomes and in mitochondria of specific peripheral tissues. Previous reports have localized the adrenal benzodiazepine receptor to the outer mitochondrial membrane. In this report, we show that the prototypic benzodiazepine, diazepam, effects a stimulation of adrenal mitochondrial cholesterol delivery similar to that observed for endozepine. The effective diazepam concentration was consistent with that previously shown to displace a high-affinity ligand of the mitochondrial benzodiazepine receptor. The action of diazepam in adrenal mitochondria suggests that the mediation of corticotropin-induced steroidogenesis may be the physiological function of the peripheral-type benzodiazepine receptor. These studies provide new insights into the previously unknown function of peripheral benzodiazepine receptors and should allow new investigations into the stimulation of steroidogenesis by endozepines and benzodiazepines in the brain and in certain peripheral tissues.

Adrenocorticotropic Hormone↗

Clinical application of sodium-23 nuclear magnetic resonance for measurement of red cell sodium concentrations.

Red cell sodium (RBC-Na+) concentrations were measured using 23Na nuclear magnetic resonance (NMR), without the destruction of erythrocyte membranes. Subjects were categorized into four groups: 20 normotensive subjects (NT group), 20 age-matched essential hypertensive patients (EHT group), 10 patients with primary aldosteronism (PA group), and 18 patients treated with digoxin (DIG group). Although RBC-Na+ concentrations were similar between the NT group (6.14 +/- 0.80 (Mean +/- SD) mmol/l) and the EHT group (5.92 +/- 0.99), they were significantly higher in both the PA group (7.55 +/- 0.88, p less than 0.001) and the DIG group (8.43 +/- 3.81, p less than 0.02). In the PA group, RBC-Na+ concentrations decreased significantly after resection of the adenoma, and there was an inverse relationship between serum potassium and RBC-Na+ concentrations (r = -0.65, p less than 0.01). In the DIG group, RBC-Na+ concentrations tended to increase in proportion to serum digoxin levels (r = 0.53, p less than 0.05). These results support the view that RBC-Na+ concentrations are determined primarily by Na+/K+-pump activity of red cell membranes. This study showed also that Na+ NMR is an useful method determining intracellular Na+ concentrations.

Digoxin↗

A unified design algorithm of two-dimensional digital filters for radioisotope image processing.

A unified design algorithm of two-dimensional digital filters for radioisotope image processing based on the Fourier-Bessel transform and the weighted least-squares method is described. The algorithm presented here can treat the various kinds of two-dimensional digital filters in a unified approach. Design examples are presented and several graphs are included to show the relationships between the design parameters as an aid in practical applications. The application of the method in radioisotope image processing is also presented. Several low-pass, Wiener and band-pass filters were designed using the method and applied to some clinical data in nuclear medicine including SPECT images. The digital filter design technique proposed here is considered to provide a powerful tool for extraction of additional qualitative information and improvement of the quality of nuclear medicine images both in research and in routine clinical work.

Algorithms↗

Hypotensive mechanisms of antihypertensives based on the water tank model.

Mechanisms of hypotensive action of antihypertensive drugs were theoretically considered using the water tank model on body fluid volume-blood pressure regulation. If a cock is attached to a tank with a base area corresponding to the reciprocal of total peripheral resistance (TPR) and water is poured into this tank at a rate corresponding to the amount of Na+ intake, then equilibrium should be achieved at a certain water level, volume, and output from the cock, which represent mean arterial pressure (MAP), cardiac output (CO), and urinary Na+ excretion rate. The height of the cock from the tank bottom and the size of the cock correspond to the x-intercept and slope of the renal function curve (pressure-natriuresis relationship). Vasodilators lowered the cock height and enlarged the base area (reduced TPR), resulting in an increase in the volume (CO). beta-Blockers not only lowered the height, but also decreased the size of the cock. Because they do not alter TPR (base area), CO (volume) must be reduced. Converting-enzyme inhibitors had the same effects on the height and size of the cock as beta-blockers, but enlarged the base area (reduced TPR), resulting in an increase in the volume (CO). Diuretics increased the cock size without affecting the cock height or the base area, resulting in a decrease in CO. The effects of antihypertensive drugs on the cock (kidney) seemed essential in their hypotensive action, similarly as abnormality of the renal function curve is essential in the genesis of hypertension. These analyses can illustrate schematically the hemodynamic changes induced by antihypertensive drugs.

Antihypertensive Agents↗

Effect of dietary sodium on the Na-K ATPase inhibitor in patients with essential hypertension.

To study the circulating humoral factor modifying transmembrane sodium transport, plasma was obtained from 12 patients with essential hypertension (EH) fed a high sodium diet (NaCl 15 to 17 g/d) for seven days and thereafter a low sodium diet (NaCl 2 to 3 g/d) for seven days. Ouabain-sensitive 86Rb+ influx into the red blood cells (RBC) obtained from a healthy subject, and incubated with the plasma obtained during the high sodium diet was significantly lower than that incubated with the plasma obtained during the low sodium diet (3.74 +/- 0.26 v 3.97 +/- 0.30 nmol/10(8) cells, P less than .05). The changes in mean blood pressure from the high to low sodium diet showed a significant positive correlation with the changes in the ouabain-sensitive Rb influx into RBC in the plasma from the high to low sodium diet. These results suggest that a humoral factor modifying the sodium pump might be altered by sodium balance in EH, especially in salt-sensitive hypertension.

Aldosterone↗

Effects of salt, prostaglandin, and captopril on vascular responsiveness in essential hypertension.

To examine the influence of dietary sodium, prostaglandin, and captopril on vascular reactivity, 12 patients with essential hypertension (EH) and seven normotensive subjects (NT) were given a high sodium diet and thereafter a low sodium diet, each for ten days. Indomethacin (IND) (150 mg/d) was administered during the last three days of each dietary period. Blood pressure and cardiac output (CO) (by impedance cardiography) were measured during the angiotensin II (Ang II) infusion before and after the IND treatment of each dietary period. In eight patients with EH, captopril 100 mg was given before Ang II infusion. EH patients were classified as either salt sensitive (SS) or nonsalt sensitive (NSS). The mean blood pressure (MBP) response to Ang II was significantly higher on high sodium intake than on low sodium intake in NSS and NT, but not in SS. IND significantly increased the MBP response to Ang II on low sodium intake in NSS and NT, but not in SS. IND significantly increased the TPR response to Ang II on low sodium intake, remarkably in NSS and NT compared with SS. Salt sensitivity (% decrease in MBP from high to low sodium intake) highly correlated with the increase in the TPR response to Ang II by IND on low sodium intake (r = -0.90). After captopril administration, IND still increased the MBP and TPR response to Ang II on low sodium intake. These results suggest that the modulation of the vascular responsiveness to Ang II by prostaglandins is altered by sodium balance and salt sensitivity in EH.

Angiotensin II↗

Different interhemispheric transfer of kanji and kana writing evidenced by a case with left unilateral agraphia without apraxia.

Recent neuropsychological studies have revealed that the processing of kanji (the Japanese morphograms) and kana (the Japanese syllabograms) involves different intrahemispheric mechanisms. We describe a patient showing left unilateral agraphia without apraxia for kanji, but not for kana, who was diagnosed by magnetic resonance imaging as having a lesion of the posterior body of the corpus callosum. This patient indicates that different neural pathways are used for kanji and kana not only intrahemispherically, but also interhemispherically.

Aged↗

Peripheral-type benzodiazepine receptors are involved in the regulation of cholesterol side chain cleavage in adrenocortical mitochondria.

In an attempt to elucidate the physiological relevance of the peripheral type of benzodiazepine receptor in adrenocortical mitochondria, we examined the effect of three different benzodiazepines (diazepam, Ro5-4864, and chlordiazepoxide) on the conversion of cholesterol to pregnenolone, the rate-limiting step in steroidogenesis, by using cholesterol-loaded mitochondria from bovine adrenal zona fasciculata. These benzodiazepines, except chlordiazepoxide, caused a dose-dependent stimulation of the cholesterol side chain cleavage in the mitochondria. The stimulatory effect of Ro5-4864 was approximately 10 times more potent than that of diazepam. No inhibitory effect of YM-684 (Ro15-1788), a potent antagonist to central-type benzodiazepine receptors, was observed in the stimulation induced by diazepam and Ro5-4864. Both external calcium ion and voltage-dependent calcium channel blocker, (+)-PN200-110, were without effect on the diazepam-induced steroidogenesis. By contrast, pretreatment of mitochondria with digitonin abolished the stimulatory effect of diazepam on the mitochondrial steroidogenesis. The present results indicate that the peripheral-type benzodiazepine receptor of adrenocortical mitochondria plays an essential role in regulating cholesterol side chain cleavage without any change of calcium channels.

Adrenal Cortex↗

Effects of intracerebroventricular atrial natriuretic factor on angiotensin II- or sodium-induced blood pressure elevation and natriuresis.

We examined the effects of intracerebroventricular (i.c.v.) administration of atrial natriuretic factor (ANF) on pressor and natriuretic responses induced by i.c.v. angiotensin II (Ang II) or hypertonic NaCl. Conscious male Wistar rats were given one of the following solutions into the lateral ventricle: artificial cerebrospinal fluid (CSF); rat ANF (99-126) 1.0 microgram/kg per min; Ang II 100 ng/kg per min; 0.6 mol/l NaCl; Ang II plus ANF, and 0.6 mol/l NaCl plus ANF. The i.c.v. infusion of artificial CSF or ANF alone did not cause significant changes in mean blood pressure, urinary volume or sodium excretion (UNaV). The i.c.v. infusion of Ang II or 0.6 mol/l NaCl raised mean blood pressure, decreased urinary volume and increased UNaV. When ANF was administered with Ang II, the Ang II-induced responses were diminished significantly (delta mean blood pressure, +10 +/- 3 versus +20 +/- 4 mmHg; delta urinary volume, -38 +/- 9 versus -78 +/- 5 microliters/min; delta UNaV, +0.49 +/- 0.51 versus +2.28 +/- 0.58 mumol/min). The centrally administered ANF opposed the effects of 0.6 mol/l NaCl, though the effect was significant only in respect of blood pressure. Our results indicate that the brain ANF may have an antinatriuretic role in some conditions.

Angiotensin II↗

Selective removal of triglyceride-rich lipoproteins by plasmapheresis in diabetic patients with severe hypertriglyceridemia.

Two diabetic patients with marked intractable hypertriglyceridemia under treatment with hemodialysis for chronic renal failure were treated by either an apolipoprotein B-dependent removal of lipoproteins using dextran sulfate cellulose column plasmapheresis or a size-dependent removal of lipoproteins using hollow-fiber filtration plasmapheresis. In one patient, a column packed with hollow fibers was used as a plasma separator and a dextran sulfate cellulose column as an adsorbent. In another patient, because the hollow-fiber column did not separate plasma from whole blood, a centrifuge-type blood cell separator was used for the plasma separation. The amounts of plasma cholesterol, triglycerides, and phospholipids removed by plasmapheresis were 30%, 33%, and 30%, respectively, when the combination of a hollow-fiber column and a dextran sulfate cellulose column was used. Corresponding values were 31%, 29%, and 27%, respectively, when the combination of the centrifuge-type blood cell separator and the hollow-fiber column was used. The efficiency of lipid removal was almost the same with both techniques. As for plasma separation, the centrifuge-type blood cell separator was more efficient than the hollow-fiber column. Some losses of albumin and platelets were observed when combination plasmapheresis using the centrifuge-type blood cell separator and the hollow-fiber column was performed. In conclusion, we prefer the centrifuge-type blood cell separator to the hollow-fiber column for plasma separation of marked hypertriglyceridemia. The second filter must be chosen for each patient according to the size of the lipoproteins.

Adult↗