Biomedical subjects
C Watanabe
Publications and source records attributed to C Watanabe.
Mechanisms of caffeine-induced contraction and relaxation of rat aortic smooth muscle.
1. Using front-surface fluorimetry and Fura-2, we determined the effects of caffeine on cytosolic calcium concentration ([Ca2+]i) and on tension of strips of the rat thoracic aorta. We also determined the effects of caffeine on 45Ca2+ influx into the strips. The objective was to elucidate the mechanism of contraction and relaxation in vascular smooth muscle, as induced by caffeine. 2. In normal physiological salt solution (PSS), caffeine induced a transient tension development, while it induced a biphasic change in [Ca2+]i. The initial transient peak in [Ca2+]i which coincided with tension development was followed by a sustained increase. Thus, changes in tension did not follow changes in [Ca2+]i. In Ca(2+)-free PSS, both the caffeine-induced contraction and the increase in [Ca2+]i were transient. It was suggested that in both the presence and absence of extracellular Ca2+, the transient increase in [Ca2+]i was due to the release of Ca2+ from the intracellular store. Although the sustained increase in [Ca2+]i depended on extracellular Ca2+, it was not affected by diltiazem, a Ca2+ antagonist. 3. Caffeine inhibited the increase in [Ca2+]i and tension development during 118 mM-K+ depolarization, in a concentration-dependent manner. The extent of reduction in tension (relaxation) was greater than that expected from the reduction in [Ca2+]i based on the [Ca2+]i-tension relationship observed with K+ depolarization. Pretreatment of the strips with ryanodine did not alter the inhibitory effects of caffeine. 4. Caffeine inhibited the increased [Ca2+]i and developed tension during stimulation by 10(-5) M-noradrenaline, in a concentration-dependent manner. 5. Dibutyryl cAMP (10(-4) M) inhibited both high K(+)-induced and noradrenaline-induced tension development. Inhibition of an increase in [Ca2+]i in relation to the inhibition of tension during noradrenaline stimulation was much greater than that in 118 mM-K+ depolarization. 6. Although caffeine per se had no effect on 45Ca2+ influx in the strips in normal PSS, caffeine did inhibit the increase in 45Ca2+ influx stimulated by 118 mM-K+ or by 10(-5) M-noradrenaline, to a similar extent and with similar IC50 values. 7. The characteristic features of the effects of caffeine on vascular smooth muscle, i.e. the transient nature of contraction and the relaxation of precontracted strips could be explained as follows: caffeine is able to reduce [Ca2+]i after releasing Ca2+ from intracellular stores; however, this may play a minor role. Independent of the [Ca2+]i reduction, the second messenger, cAMP, might directly influence the [Ca2+]i-tension relationship, and if so, would play a major role.
[A clinicopathologic study of atrial infarction complicating left ventricular posterior myocardial infarction].
Among a series of 400 consecutive autopsy cases we performed a clinicopathologic study of atrial infarction in 46 autopsy-proven cases, which had acute or old left ventricular (LV) myocardial infarction. We used blocks taken from both atrial appendages, the region of the sinus-node, the lateral wall of the right atrium, the posterior wall of the right atrium, and the posterolateral wall of the left atrium. Atrial infarction was identified in 13 (28%) of 46 cases with LV posterior infarction which was caused by lesions of the right coronary artery; 10 cases were right atrial infarction and 3 were both right and left atrial infarction. Among 13 cases in which the acute phase of ventricular infarction could be followed, 3 cases exhibited transient atrial fibrillation. Of these 3 cases, 2 had atrial infarction. The mean stenotic index of the proximal right coronary artery was 4.3/5 in the 13 cases of atrial infarction, 3.2/5 in 17 cases of acute necrosis or scar and 3.1/5 in 16 cases without ischemic atrial lesions. Most of the atrial infarction was found in the right atrium; 10 in the right atrial appendage, 8 in the right atrial lateral wall, 3 in the region of the sinus node and the left atrial posterolateral wall, 2 in the right atrial posterior wall, and one in the left atrial appendage. In conclusion, the incidence of atrial infarction was unexpectedly high (28%) in LV posterior infarction caused by lesions of the proximal right coronary artery, particularly in severe stenosis or obstruction.
[A clinicopathologic study of morphologic tricuspid valve prolapse in the aged: comparison with color Doppler evaluation].
Similar morphologic abnormalities have often been observed in the leaflets of tricuspid valve in patients with mitral valve prolapse. In the present study, morphologic tricuspid valve prolapse was analyzed in 500 consecutive autopsies of the aged over 60 years (mean 78.5 yrs, 266 men, 234 women). Additionally, the sensitivity and specificity of the color Doppler technique applied before death were assessed in 61 autopsy cases. The results were as follows: 1. The incidence of morphologic tricuspid valve prolapse was 22.2% at autopsy in 500 cases of the aged, however, tricuspid regurgitation had not clinically been detected in any of them. 2. The prolapse of 2- or 3-leaflets was common (78.5%). Among the 3 leaflets, the prolapse was more frequently observed in the anterior or posterior leaflet than in the septal leaflet. Combined tricuspid and mitral valve prolapses were observed in 22 cases (19.8%). 3. Among 61 cases examined by color Doppler echocardiography, autopsy showed that 16 cases had tricuspid valve prolapse and 14 cases tricuspid regurgitant flow signals (87.5%). 4. Regurgitant flow signals were also detected in 4 of 12 morphologically normal cases (33.3%). 5. In autopsy cases of the aged, generally, the incidence of morphologic tricuspid valve prolapse and tricuspid regurgitant flow signal were high, however, hemodynamically significant regurgitation due to prolapse was very rare.
[Ocular penetration of UF-021, a new prostaglandin related compound, in the rabbit eye].
The ocular penetration and pigment affinity of topically applied UF-021, a newly developed prostaglandin-related compound, were investigated in rabbit eyes using 3H-labeled UF-021. Ten minutes to 24 hours after instillation of 0.12% of 3H-UF-021 solution into New Zealand white or pigmented rabbit eyes, the rabbits were sacrificed and the eyes were immediately enucleated. The extraocular muscles, conjunctiva, aqueous humor, cornea, iris, anterior and posterior sclera, ciliary body, lens, vitreous, retino-choroid complex, optic nerve were separated and blood samples were taken. The concentration of 3H-UF-021 in each sample was determined with a liquid scintillation counter. The peak concentration of UF-021 was obtained at 40 minutes and 1 hour after instillation in the iris-ciliary body and aqueous humor of albino rabbit. According to the pharmacokinetic analysis of the data, UF-021 showed good ocular penetration into the rabbit eye, and the permeability of the epithelial barrier for UF-021 was calculated to be 2.9 x 10(-3) cm/hr. The apparent elimination rate constant and the apparent absorption rate constant were also calculated to be 0.21 hr-1 and 1.28hr-1, respectively. The time course for 3H-UF-021 concentration in the eye of pigmented rabbit was almost the same as that in the eye of non-pigmented rabbit, indicating that UF-021 did not bind to pigmented tissues.
A change in the spontaneous release of endogenous acetylcholine from rat striatal slices after repeated injection of haloperidol.
The spontaneous and 50 mM K(+)-stimulated release of endogenous acetylcholine (ACh) from rat striatal slices was measured to investigate an adaptive change of striatal ACh after a withdrawal period for 24 h from chronic treatment of the rat with haloperidol. The haloperidol injections (2.5 mg/kg/day) for a period of 3, 7 or 14 days all reduced the spontaneous release of ACh significantly by 20-50% without changing tissue levels of ACh. On the contrary, these treatments produced a very small (by about 10%) but significant increase in K(+)-stimulated release except for the treatment of 7 days. These results suggest that the spontaneous ACh release is under the control of a dopaminergic mechanism, which might be different from the mechanism controlling the evoked release of ACh and emerges following withdrawal from chronic haloperidol treatment.
Structure and function in recombinant HIV-1 gp120 and speculation about the disulfide bonding in the gp120 homologs of HIV-2 and SIV.
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Gastric mucosa in female patients with fundic glandular polyps.
To evaluate the characteristics of the gastric mucosa in women with fundic glandular polyps, we examined gastric acid secretion, fasting serum levels of pepsinogen I and gastrin, and gastric histology in 11 female patients with fundic polyps, and compared the results with 30 female controls without endoscopic abnormalities and 50 female patients with gastric foveolar hyperplastic polyps. No significant difference was found in gastric and secretion and fasting serum levels of pepsinogen I and gastrin between the patients with fundic glandular polyps and the control subjects. Histological examination showed that atrophic gastritis was generally not found in the patients with fundic glandular polyps. In contrast, gastric acid secretion and fasting serum levels of pepsinogen I were significantly lower and serum gastrin levels were significantly higher in the patients with foveolar hyperplastic polyps than in the other two groups. Also, patients with foveolar hyperplastic polyps had a higher prevalence and further advanced atrophic gastritis in the fundus than did the other two groups. Our investigations demonstrated that fundic glandular polyps arise from gastric mucosa without atrophic gastritis, whereas foveolar hyperplastic polyps develop from mucosa affected by atrophic gastritis, especially type A gastritis.
Lack of correlation between P pulmonale and right atrial overload in chronic obstructive airways disease.
The correlation between P pulmonale and right atrial overload in chronic lung disease was studied. Right atrial pressure, pulmonary artery pressure, and cardiac output were measured with a Swan-Ganz catheter in nine patients with chronic lung disease and P pulmonale on the electrocardiogram (P wave amplitude of greater than or equal to 2.5 mm (0.25 mV) in leads II, III, and a VF. The results were compared with those in six patients with an atrial septal defect (left to right shunt greater than or equal to 50%) and six patients with pulmonary hypertension (mean pressure greater than or equal to 30 mm Hg without left sided heart disease). Right atrial volume and wall thickness were measured in 10 cases of P pulmonale among 1000 necropsy cases and compared with 141 normal hearts from the same series. The patients with P pulmonale did not show a significant increase in right atrial or pulmonary artery pressures. None of the patients with an atrial septal defect or pulmonary hypertension had P pulmonale on the electrocardiogram. In the necropsy cases of P pulmonale mean (1 SD) in right atrial volume (32 (12) ml) and wall thickness (1.5 (0.7) mm) were not significantly increased (40 (14) ml and 1.4 (0.5) mm in the normal hearts). There was a significant inverse relation between the presence of P pulmonale and the cardiothoracic ratio. In all the patients with P pulmonale chest x ray showed a low cardiothoracic ratio, a considerably depressed diaphragm, and a pendulous heart. This study showed no correlation between P pulmonale and right atrial overload in chronic lung disease. A more vertical anatomical position of the heart, particularly of the right atrium, seems to be the major factor responsible for generation of P pulmonale in chronic airways disease.
[Systolic anterior motion of the anterior mitral leaflet and/or the chordae tendinae in the elderly].
Systolic anterior motion of the anterior mitral leaflet and asymmetric septal hypertrophy (ASH) are characteristic features of hypertrophic obstructive cardiomyopathy (HOCM) on an echocardiogram. Among 9,670 patients over 60 years old examined by echocardiography from January, 1984 to October, 1990, 55 patients showed systolic anterior motion of the anterior mitral leaflet and/or the chordae tendinae (SAM). We investigated clinical features and morphological features of the left ventricle on an echocardiogram in the 55 patients with SAM. They were classified into three groups according to the degree of SAM. Thirty eight cases (group I) had no mitral and/or chordal-septal contact, 10 (group II) had brief contact (less than 30% on the echocardiographic systole) and 7 (group III) had prolonged contact (greater than or equal to 30%). Ages ranged from 60 to 99 with a mean age of 78.2 years. There were 19 males and 36 females and there was a predominance of females in each group. Thirty five cases had hypertension and 34 left ventricular hypertrophy on electrocardiograms. One case of group I, 3 of group II and 7 of group III had a clinical diagnosis of HOCM. In comparison with each group, the incidence of LVH (SV1 + RV5 greater than or equal to 35 mm) was 52% in group I, 90% in group II and 83% in group III and that of LVH (SV1 + RV5 greater than or equal to 70 mm) was 29%, 20% and 67%, respectively. On echocardiographic examination, the diastolic descent rate of the anterior mitral leaflet in the 3 groups was 36.1 +/- 13.1 mm/sec, 19.4 +/- 13.1 mm/sec and 10.7 +/- 11.8 mm/sec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of water on the transverse strength of posterior composite resins.
In an attempt to evaluate the influence of water on the mechanical properties of composite resin, the transverse strengths of 15 commercially available composites were determined in water at 37 degrees C and compared with the strength measured in air after storage in water for periods of 1 day to 3 months. Some of the composites, including two which contained a blend filler, showed remarkable reduction of transverse strength when measured in air, according to the procedures specified in ISO 4049, in comparison with transverse strength measured in water. The change of water content in the material can predominantly affect the mechanical behavior of composite resin.
[Morphological observation of the mitral annulus fibrosus (II)].
In 1986, Hutchins observed a high incidence of the disjunction of the mitral annulus fibrosus in mitral valve prolapse syndrome. However, we could not prove his view in our previous study using one section in each case. In this study, the types of mitral annulus fibrosus were analyzed in plural sections. Autopsy hearts of nine aged cases were used for examination of the mitral annulus fibrosus in five to eight longitudinal sections from the posterolateral wall. The types of the mitral annulus fibrosus were classified as; Type A (the mitral valve attaches to the left ventricle), Type B (the valve attaches to the left atrium), Type C (the atrialis layer of the valve continues to the left atrium, while the fibrosa layer continues to the left ventricle), and type D (mitral annulus calcification). A1-3 and B1-3 are subtypes. In the nine cases there were no consistent patterns in type distributions. All sections showed Type A1 (Case 2), Type A1 to A3 (Case 5), and Type B1 to B3 (Case 8). In other cases, a combination of Type A and B (Case 4, 6, 7, 9), and inclusion of Type C (Case 1) and Type D (Case 3) were found. The location of the middle scallop of the posterior mitral leaflet corresponded to the section of the previous study. Among three cases of Type A in the middle scallop, two showed Type A in every section. Among five cases of Type B in the middle scallop, only one case showed Type B in every section. Other four cases showed various combinations with the other types. A case of Type D in the middle scallop showed also Type B and Type C. The conclusion of this study was that in 1/3 of the cases, the type of the mitral annulus fibrosus was consistent, but in the other 2/3 they were not consistent. In other words, one section is not necessarily representative of the morphology of the mitral annulus fibrosus in each case.
Toxicity modification of sodium selenite by a brief exposure to heat or cold in mice.
The effect of a brief exposure to heat/cold on the subsequent development of toxicity of sodium selenite (SS) was evaluated in male ICR mice. Mice were exposed to one of three ambient temperatures (Ta; approx. 8 degrees, 22 degrees and 33 degrees C). One and a half hours after the beginning of the exposure, they were injected with 45 mumol/kg of SS subcutaneously. The exposure was terminated 3 h after injection and the mice were returned to Ta of 22 degrees C. Heat-induced enhancement of toxicity was recognized in some plasma enzyme activities 3 days after injection and in the suppression of body weight for up to 3 weeks. On the other hand, cold exposure alleviated SS toxicity in terms of these indices. Thus, the Ta during this short period was recognized to be important in determining subsequent development of SS toxicity. At the end of the thermal exposure, heat increased renal concentration of the injected Se. On the other hand, in the liver and the other organs examined, the highest Se concentration was found in the cold-exposed group, followed by the control (room temperature) and the heat-exposed. The relation between the modification of toxicity and the altered distribution was not clear. Neither glutathione level in the liver nor that in the kidney at the time of SS injection could explain the observed modification of the toxicity.
Modification by nickel of instrumental thermoregulatory behavior in rats.
The effects of NiCl2 on the colonic temperature and thermoregulatory behavior (TRB) of rats were examined. TRB was evaluated in an instrumental (operant) setting in which rats were required to press a level to obtain convectional heat (SEEK) or to avoid heat (ESCAPE). Orthogonal polynomial regression was used to describe the response patterns in both the SEEK and ESCAPE situations. Two milligrams per kilogram of Ni (ip) caused rapid, transient hypothermia at an ambient temperature of 21 degrees C. When given access to heat reinforcement, rats responded for heat at a lower rate immediately after 2 or 5 mg/kg of Ni (up to 5-15 min) than after saline. Subsequently, response rates rose 30 min or more after Ni injection. A converse pattern was found with the heat escape situation. These observations, confirmed by two contrasting procedures, indicate that the changes were thermoregulatory in nature and cannot be explained by nonspecific suppressive or excitatory effects of Ni. They further suggest that Ni-induced hypothermia results from an altered body temperature set point. The subsequent reversal in behavior probably arises from a direct action of Ni on autonomic effector mechanisms. The origin and biological significance of these findings require further investigation. Physical requirements and response topography are discussed as critical variables in the interpretation of experiments requiring similar responses under different ambient temperatures.
Transient hypothermia and hyperphagia induced by selenium and tellurium compounds in mice.
The effects of sublethal doses of selenite, selenate, selenocystine (Se-Cys) and selenomethionine (Se-Met) as well as of tellurite on body temperature and feeding behavior were examined in male ICR mice. Ten or 30 mumol/kg of chemicals were injected subcutaneously and body temperature was measured up to 4 h. In a separate experiment, the gastric content was weighted 4 h after injection. All chemicals except Se-Met induced both hypothermia and hyperphagia, suggesting that: (a) these two effects are related to each other; (b) among the chemicals tested, Se-Cys appears to be the most potent hypothermia inducer; (c) Se-Met is unique in that it has neither effect.
Possible role of cementoblasts in the resorbant organ of human deciduous teeth during root resorption.
Human deciduous teeth undergoing physiologic root resorption were extracted and fixed with a mixture of formaldehyde and glutaraldehyde and processed for scanning (SEM) and transmission (TEM) electron microscopy, and for acid (ACPase) and alkaline phosphatase (ALPase) cytochemistry. The resorbant organ, rich in odontoclasts, cementoblasts, fibroblasts, and macrophages, formed prominent resorption lacunae in root dentin. SEM observations of resorption lacunae treated with trypsin solution showed islands of newly-formed cementum matrix in part of the resorbing dentin surfaces. Such cementum consisted of bundles of densely-arranged collagen fibrils and, in part, contained forming cementocytic lacunae and canaliculi. Active cementoblasts adjacent to odontoclasts on resorbing dentin surfaces showed cuboidal outlines and were characterized by the presence of numerous cisterns of rough endoplasmic reticulum, well-developed Golgi complexes, secretion granules, and many mitochondria. They sometimes formed a thin layer of cementoid and/or cementum matrix upon the resorbing dentin surface. These cementoblasts had ACPase-positive lysosomes in the cell bodies and exhibited intense ALPase activity along the plasma membranes of whole cell surfaces. These results suggest that, during root resorption, 1) active cementoblasts are present adjacent to active odontoclasts and 2) these cementoblasts are involved in remodeling the resorbing dentin surfaces.
Cellular roles in physiological root resorption of deciduous teeth in the cat.
This study has attempted to assess the importance of mesenchymal cells, fibroblasts, cementoblasts, and mononuclear phagocytes (i.e., macrophages) in physiological root resorption of feline deciduous teeth. Deciduous incisors of three- to six-month-old kittens undergoing root resorption were investigated by means of electron microscopy. In an early phase of root resorption, the resorption organ consisted of many fibroblasts and relatively few macrophages and odontoclasts, the last with a wide, clear zone and narrow, immature, ruffled border. In the active phase of root resorption, the resorption organ contained many odontoclasts with a well-developed ruffled border and a reduced clear zone, cementoblasts, fibroblasts, macrophages, neutrophils, and many blood vessels. Cementoblasts were present usually on the resorbing dentin surface adjacent to odontoclasts and, in many cases, these cells communicated with each other via gap junctions. Cementoblasts frequently extended broad cell processes with secretion granules and with phagosomes containing collagen fibrils into the dentinal tubules exposed to resorption lacunae. Some macrophages exhibiting a clear zone-like structure also appeared on resorbing dentin surfaces. In the resting phase of root resorption, the dentin surface was covered mostly with cementoblasts resembling bone lining cells. There was an occasional macrophage, but no odontoclasts were observed during this phase. During removal of the periodontal ligament concomitant with root resorption, many fibroblasts phagocytosed mature collagen fibrils, as well as amorphous fluffy material. These results suggest that these mesenchymal cells, as well as odontoclasts, are essential for the cellular removal of dental hard and soft tissues during shedding of feline deciduous teeth.
[A clinical study of hypertrophic obstructive cardiomyopathy in the elderly].
Seven elderly patients with hypertrophic obstructive cardiomyopathy (HOCM), who had the three following characteristics on echocardiograms 1) extremely thickened septum, 2) systolic anterior motion of the mitral valve, 3) mid systolic semi-closure of the aortic valve, were clinically evaluated. Ages ranged from 73 to 86 years old (average 78.9% yr.) and all were women. None had not a family history of hypertrophic cardiomyopathy but they had mild hypertension. Six patients showed a significant high voltage on the ST-segment and T-wave abnormalities ("strain" pattern). The left ventricular posterior wall as well as the septum was thickened in 5 and the remaining 2 showed asymmetrical septal hypertrophy (ASH) on echocardiograms. The left ventricular cavity was narrowed due to left ventricular hypertrophy and the shape of the left ventricular cavity was ovoid in all patients. The aorto-septal angles in these 7 patients were 80 degrees to 120 degrees. In addition, proximal septal bulge in all and anterior displacement of the mitral posterior leaflet due to the mitral ring calcification (MRC) in some patients contributed to the narrowing of the left ventricular outflow tract, and the mitral valve was pulled up toward the septum because of the good left ventricular systolic function (ejection fraction: 70 to 94% by echocardiography) and blood was ejected at a high velocity through a narrowed outflow tract (Venturi effect). Pressure gradients in the left ventricular outflow tract was 38 to 146 mmHg in 5 examined by cardiac catheterization. Biopsy specimens were obtained from 2 patients, showing hypertrophic myocytes (diameter: 20 to 30 micron) in 2 and mild disarray in 1.(ABSTRACT TRUNCATED AT 250 WORDS)