Biomedical subjects
Publications and source records attributed to M Kawamura.
A case of extrahepatically growing hepatocellular carcinoma is reported, and the Japanese literature is reviewed. A 42-year-old man was admitted to our hospital on December 27, 1985 complaining of epigastralgia and nausea. Ultrasonography and computerized tomography showed a large tumor in the right hepatic lobe. This Was removed surgically and examined histologically.
Connective tissue outgrowths of neonatal muscle onto a substratum of bone matrix differentiate into cartilage in response to a bone morphogenetic protein (BMP). The BMP can be separated from bone matrix by extraction with 4 M guanidine hydrochloride (GuHCl) or degraded in situ by endogenous proteolytic enzymes to deactivate the matrix. Rat triceps muscle was minced in a suspension of noncollagenous bone matrix proteins including BMP (BMP/NCP) in culture medium. To investigate the possible synergistic interactions in induced chondrogenesis, six biosynthesized, highly purified growth factors were similarly added to the culture alone or in combination with BMP. Human interleukin-1 (IL-1) and Forskolin were also introduced to test the effects on BMP/NCP-induced chondrogenesis. On Day 14 of cultivation, [3H]thymidine incorporation into DNA and [35S]sulfate incorporation into glycosaminoglycans (GAG) were measured, and the values were expressed as percentages of the control. The quantity of induced cartilage formation was estimated by a histomorphometric scoring system. Under the influence of BMP/NCP, cultures grew on deactivated matrix, incorporated 55% more [3H]thymidine into DNA, incorporated 115% more [35S]sulfate into GAG than control cultures, and differentiated into cartilage. Without BMP/NCP, growth factors, IL-1, and Forskolin did not produce a comparable incorporation of either [3H]thymidine or [35S]sulfate, and they induced differentiation of fibrous tissue only. In the presence of BMP/NCP, cartilage developed in nearly all cultures. When the media were supplemented with growth factors, measurable increases in uptake of [3H]thymidine occurred with human epidermal growth factor (h-EGF), insulin-like growth factor-1 (IGF-1), nerve growth factor (NGF), transforming growth factor-beta (TGF-beta), bovine acidic fibroblast growth factor (baFGF), IL-1, bovine basic fibroblast growth factor (bbFGF), and Forskolin. Measurable increases in uptake of [35S]sulfate into GAG occurred with IL-1, baFGF, TGF-beta, h-EGF, IGF-1, bbFGF, NGF, and Forskolin. Synergistic interaction with BMP was considered when the quantity of cartilage developed (on a scale of 0-12 scores) in excess of the quantity of Score 4 induced by BMP/NCP alone. A cytokine, IL-1, had the greatest effect (Score 9). TGF-beta (Score 7), baFGF (Score 6), and NGF (Score 6) had relatively little effect. h-EGF, IGF-1, bbFGF, and Forskolin had no effect on cartilage development.(ABSTRACT TRUNCATED AT 400 WORDS)
The hypotensive effects of some antihypertensive drugs are augmented under sodium restriction, while those of others are not. The mechanisms of these interactions were theoretically analyzed based on the arterial pressure-natriuresis relationship. Four-week studies were performed in 24 patients with essential hypertension who were given a regular sodium diet (12-15 g of NaCl/d) in the first and third weeks and a sodium-restricted diet (1-3 g/d) in the second and fourth weeks. One of three antihypertensive drugs, 60 mg/d of nicardipine (Ca-antagonist), 120 mg/d of propranolol (beta-blocker) or 150 mg/d of captopril (converting-enzyme inhibitor) was administered in the third and fourth weeks. The mean arterial pressure and urinary sodium excretion were measured on the last three days of each week. The degree of interaction between the antihypertensive drugs and sodium restriction was statistically compared. The hypotensive effect of nicardipine and propranolol did not differ with the change in sodium intake, whereas that of captopril was greater under sodium restriction than under the regular sodium diet. Urinary sodium excretion was plotted on the ordinate as a function of arterial pressure before and after administration of the antihypertensive drugs. The pressure-natriuresis curve was shifted left, without a change in the slope, by nicardipine and propranolol and also left, but with a decrease in the slope, by captopril. The hypotensive effect of nicardipine and propranolol, being independent of the amount of sodium intake, was based on the leftward shift of the pressure-natriuresis curve that was probably due to the decrease in renal vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
The membrane bound (Na,K)-ATPase prepared from Artemia salina nauplii was solubilized with a zwitterionic detergent, 3[3(cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), and then purified on a Bio-Gel A-1.5 m column in the presence of the detergent. 1) Upon solubilization, both NaCl and KCl protected the enzyme against loss of activity, KCl being more effective than NaCl. 2) Gel filtration of the solubilized enzyme on a Bio-Gel A-1.5 m column in the presence of 5 mM CHAPS resulted in loss of the enzyme activity even when one of the cations was added. Most of the phospholipids in the solubilized enzyme preparation were removed during the gel filtration (delipidation) and 10-25 phospholipids were left on a protomer (alpha beta) of the enzyme irrespective of the cation present during the gel filtration. With the addition of exogenous phospholipids, the activity was restored. The activity of the enzyme delipidated in the presence of KCl was restored to 3-4 times higher than in the case of that delipidated in the presence of NaCl. 3) Relipidation experiments with a fluorescent phospholipid, dansyl phosphatidylethanolamine (Dans-PE), suggested that the enzyme delipidated in the presence of KCl reassociated with phospholipids more firmly than the enzyme delipidated in the presence of NaCl. From these results we concluded that K+ stabilized the (Na,K)-ATPase more effectively than Na+, even when the enzyme was delipidated.
We measured components of the cerebrospinal fluid renin-angiotensin system from patients with essential hypertension under different dietary sodium intakes. The cerebrospinal fluid concentration of angiotensin II (Ang II) from the patients on a normal-sodium diet was 1.36 +/- 0.41 fmol/ml (n = 5). Neither the inactive nor the active form of renin was detected by the enzymatic activity or by the immunoreactivity, whereas angiotensinogen was detected (38.6 +/- 3.1 pmol/ml, n = 5). The Ang II level remained unchanged even after incubation of the cerebrospinal fluid at 37 degrees C for 3 h. Further, when authentic Ang II was added to the cerebrospinal fluid followed by incubation for 3 h at 37 degrees C, more than 90% of the added Ang II remained unchanged. Thus, the cerebrospinal fluid Ang II level may be reflected by the activity of the brain Ang II-forming system, as it was not affected by the cerebrospinal fluid constituents. The circulating renin-angiotensin system was stimulated by sodium depletion, and the cerebrospinal fluid concentration of Ang II also increased significantly. Sodium depletion may stimulate the brain Ang-II forming system, as it does the circulating renin-angiotensin system.
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The objective of this study was to evaluate the renal actions of atrial natriuretic peptide (ANP) in the unilateral postischemic kidney of anesthetized dogs with a severe reduction in glomerular filtration rate. The dose of atrial natriuretic peptide (50 ng.kg-1.min-1) we gave did not alter the mean systemic arterial pressure, renal blood flow, and glomerular filtration rate in the normal kidney, as determined in foregoing studies. ANP was infused into the intrarenal artery continuously for 60 min after the release from 45 min of complete renal artery occlusion. In the vehicle-infused group, the glomerular filtration rate fell dramatically (6% of control), the renal blood flow decreased (60% of control), and the mean systemic arterial pressure tended to increase (136% of control). The urine flow rate and urinary excretion of sodium decreased significantly (25 and 25%, respectively) at 30 min after reflow in the postischemic period. Continuous renal artery infusion of ANP resulted in a marked increase in urine flow rate (246% of control) and the urinary excretion of sodium (286% of control). The administration of ANP led to an improvement in renal blood flow (99% of control) and glomerular filtration rate (40% of control), and attenuated the rise in mean systemic arterial pressure (109% of control), compared with findings in the vehicle-infused group. Plasma renin activity and prostaglandin E2 concentration in the renal venous blood were elevated after the release from complete renal artery occlusion in both groups. These results indicate that the vascular effects of ANP on the postischemic kidney were enhanced and that the peptide maintained the natriuretic effect.
Intracellular pathways of renin secretion were examined by use of rat renal cortical slices. Renin was labeled with [35S]methionine by incubating the cortical slices for 2 h. The labeled immunoprecipitable renin was found in microsomal fraction (F1) but not in the renin granule fraction (F2). The newly synthesized and radiolabeled renin was secreted from the incubated slices into the medium. The rate of secretion of the labeled renin activity was not increased by 10(-6) M isoproterenol, whereas secretion of total renin activity was markedly stimulated. The isoelectric focusing patterns of renin in F1 and F2 were compared with those secreted with or without isoproterenol. The pattern of F1 was similar to that secreted in the medium without stimulation. These studies suggest that a constitutive pathway exists for renin secretion from the kidney and that the constitutive (nonstimulable) pathway is responsible for the secretion of newly synthesized renin and that it is not stimulated by a beta-adrenergic mechanism.
We have purified to homogeneity a protein from bovine adrenal (fasciculata) cells that is capable of: 1) stimulating synthesis of pregnenolone (in a concentration-dependent fashion) by mitochondria when added with exogenous cholesterol; 2) increasing the concentration of cholesterol in outer and inner membrane when added to mitochondria with exogenous cholesterol; 3) increasing the rate of transport of cholesterol from outer membrane to inner membrane when the two membranes are incubated together in an aqueous buffer and subsequently separated by centrifugation; and 4) increasing the proportion of molecules of C27 side-chain cleavage P-450 that are bound to the substrate cholesterol. The protein is homogeneous according to two-dimensional polyacrylamide gels, shows a molecular weight of 8200 and is therefore referred to as 8.2 K. It is proposed that 8.2 K may be involved in the regulation of steroid synthesis in bovine fasciculata cells, possibly by stimulating entry of cholesterol into the outer membrane and by altering the intramitochondrial distribution of this substrate.
The purpose of this study was twofold. The first objective was to measure the periodontal status and perceptions of oral health in adolescents. The second objective was to determine the effects that a program of dental health education would have on their periodontal status and perceptions of oral health. The dental health education with a 90-minute lecture had been given to eleventh-grade students (352) in the previous year. The dental health education program was not carried out in tenth-grade students (442) yet. The oral examination was performed by a dentist for both grades. The examination time was about ten seconds per person. The students' periodontal status was scored as "excellent (+2)," "good (+1)," "questionable (0)," "poor (-1)," or "very poor (-2)" according to the criteria of an Oral Rating Index (ORI) System proposed by the present authors. The level of students' perceptions was assessed by the cognition score of our dental health test (10 items concerning dental attitudes and behavior). Main results were as follows: 1. Only 6% of the 10-th grade students were judged as having "excellent (+2)" oral health. Thirty-six percent were "very poor (-2)" or "poor (-1)" periodontal status. 2. The mean cognition score and the mean ORI score of the 11-th grade students were significantly greater for each sex group than those of the 10-th grade students. 3. The cognition score showed a clear relationship to the ORI score in each grade and in all. The behavioral component of the cognition score was more closely related to the ORI score. These findings suggest that the dental health education contributes to the improvement of periodontal status as well as that of perceptions. Furthermore, the ORI may be utilized for a screening system to evaluate adolescents' periodontal status quickly and effectively.
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We determined concentrations of atrial natriuretic peptide (ANP), angiotensin (Ang), norepinephrine (NE) and electrolyte in plasma and cerebrospinal fluid (CSF) to study possible roles of these substances within the brain in human hypertension. Blood and CSF samples were obtained from 10 patients with mild to moderate essential hypertension (EHT) aged 40-65 y and 10 age-matched normotensive subjects (NT) on a regular salt diet (8 g/day). Levels of ANP, NE, Na, K, Ca and Cl in CSF and plasma were comparable between EHT and NT. Plasma renin activity, plasma and CSF Ang II were lower in EHT than NT. CSF Ang III tended to be lower in EHT. There was no correlation between CSF and plasma ANP, or between CSF and plasma Ang II. Our results indicate that CSF levels of ANP may not be altered in middle aged patients with mild to moderate hypertension. It is also suggested that Ang II, NE and sodium in the central nervous system may not have important roles in hypertension of those patients.
To assess the released form of atrial natriuretic peptide (ANP) during atrial distension, we compared the form of ANP before and during atrial distension in anesthetized dogs, using radioimmunoassay combined with high performance liquid chromatography (HPLC). When increasing the left atrial pressure (LAP) from 2.2 +/- 0.9 mmHg to 9.4 +/- 1.3 mmHg, the plasma ANP concentration in the coronary sinus was increased by 190% over the control, during left atrial distension. The major form of the released ANP extracted in the blood sample obtained from the coronary sinus was alpha-form. However other unidentified immunoreactive peaks, preceding and following the main peak were also discernible. These results suggest that the major form of ANP released during left atrial distension was the alpha-form.
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The correlation between low-density lipoprotein (LDL) receptor activity and concentrations of lipids and apolipoproteins in serum was examined in 12 subjects with heterozygous familial hypercholesterolemia (FH) and in four with non-FH type II hyperlipoproteinemia. Concentrations of high-density lipoprotein cholesterol and of apolipoproteins (apo) A-I, C-II, and C-III were significantly positively correlated with LDL receptor activity, whereas LDL receptor activity was significantly inversely correlated with LDL cholesterol and apo B concentrations, and with apo ratios B/A-I and B/A-II. Neither total serum cholesterol, triglyceride, phospholipid, apo A-I, nor apo E concentrations correlated significantly with LDL receptor activity. Multiple regression analysis, with LDL receptor activity as the dependent variable, revealed concentrations of apo B and apo C-II to be the principal determinant factors. To confirm this, we subsequently calculated the LDL receptor activities before and after administration of CS-514, an inhibitor of hydroxymethylglutaryl-CoA reductase (EC 1.1.1.88), which increases the hepatic LDL receptor activity and decreases the concentration of cholesterol in serum. This drug increased calculated LDL receptor activities significantly, with a significant decrease in serum cholesterol.