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R Hosokawa

Publications and source records attributed to R Hosokawa.

53 records · Page 3Linked to original sources

Evaluation of myocardial viability with iodine-123-BMIPP in a canine model.

UNLABELLED: The tracer 123I-BMIPP was examined for its ability to reflect myocardial lipid metabolism. Studies in mice indicate that myocardial BMIPP uptake correlates with ATP content. Details, however, of myocardial accumulation in the ischemic period with either infarct or ischemia are not well documented. METHODS: Sixteen adult mongrel dogs were investigated. The occluded left anterior descending artery (LAD) alone was reperfused to make the ischemic area, and the first diagonal branch of the LAD was kept occluded to make the infarct area. Regional wall motion was evaluated by echocardiography in the short-axial view from the epicardium. Tissue blood flow was calculated using nonradioactive colored microspheres. Changes in blood glucose levels, lipid levels and lactate extraction were examined in blood collected from the aorta and great cardiac vein (GCV). The ATP concentration and BMIPP count were determined by high-performance liquid chromatography and gamma-counter, respectively. RESULTS: Two hours after reperfusion, blood flow decreased to 20% +/- 5% in the infarct area and 64% +/- 9% in the ischemic area (p < 0.05), despite comparable wall-motion reduction (32% +/- 5% and 42% +/- 12% in the infarct and ischemic areas, respectively). BMIPP content and ATP concentration showed parallel reduction: 40% +/- 7% and 75% +/- 4% (p < 0.05) of BMIPP and 32% +/- 9% and 69% +/- 7% (p < 0.05) of ATP in the infarct and ischemic areas, respectively. The nonesterified fatty acid extraction, defined as flow x ([artery] - [GCV]), decreased to 87% +/- 5.6% during occlusion and 75% +/- 20.1% 2 hr after reperfusion, as compared with the control value. CONCLUSION: BMIPP uptake correlated well with lipid metabolism and tissue ATP levels and may prove useful in differentiating myocardial infarction from ischemia in the acute phase of ischemic episodes.

Adenosine Triphosphate↗

Metabolic fate of iodine-123-BMIPP in canine myocardium after administration of etomoxir.

UNLABELLED: To clarify the metabolic fate of 123I-(-p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in dysfunctional myocardium, a comparison between normal dogs and those with etomoxir administration was studied using an open-chest canine model. METHODS: Using open-chested dogs under anesthesia, we created a system to release all the blood in the great cardiac vein outside without recirculation, if necessary. Iodine-123-BMIPP was directly injected into the left anterior descending artery, its extraction, retention and washout rate in the early phase were calculated, and the metabolites in the myocardium were evaluated using a high-performance liquid chromatography. Moreover, these factors were compared between normal dogs and those pretreated with etomoxir, that creates a condition similar to ischemia. RESULTS: Although rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged, early washout (8 min) of radioactivity significantly increased (49.6% +/- 13.3%-->70.5% +/- 10.7%, p < 0.05) with etomoxir. The levels of the full metabolite formed by complete oxidation of BMIPP decreased significantly with etomoxir (21.4% +/- 10.9%-->5.5% +/- 3.5%, p < 0.01). In addition, back diffusion of BMIPP increased (25.1% +/- 8.0%-->41.9% +/- 12.0%, p < 0.05) in the etomoxir-treated animals without affecting the levels of alpha-oxidation metabolite and the intermediate metabolites. CONCLUSION: BMIPP is very sensitive to etomoxir and is suitable for assessing mitochondrial dysfunction. Iodine-123-BMIPP might be a promising radiopharmaceutical for the evaluation of ischemic heart disease, cardiomyopathy and mitochondrial encephalomyopathy.

Animals↗

Metabolism and kinetics of iodine-123-BMIPP in canine myocardium.

UNLABELLED: The kinetics and metabolic fate of 123I-15-(p-iodophenyl)-3-(R,S)- methylpentadecanoic acid (BMIPP) in canine myocardium were studied in an open-chest dog model. METHODS: After left anterior descending artery injection of BMIPP, blood samples were collected from the corresponding great coronary vein (V) and femoral artery (A). On the basis of the A-V radioactivity difference as well as the HPLC elution profile at various time points, myocardial extraction, retention and metabolism of BMIPP were evaluated. RESULTS: BMIPP was instantly extracted from the plasma into the myocardium (74% of the injected dose) and was then retained (65.3%). Washout of the retained radioactivity was low (8.7%) and most of the washout was as alpha- and beta-oxidation metabolites (2.3 + 2.9 + 1.4%), with little loss of BMIPP itself (2.1 %). CONCLUSION: BMIPP is suitable for static SPECT imaging of the myocardium, and its slow washout appears to be due to metabolism through alpha- and beta-oxidation.

Animals↗

Effects of nisoldipine in silent myocardial ischemia after healing of acute myocardial infarction.

Silent myocardial ischemia occurring after acute myocardial infarction is classified as Cohn type II and has a frequency of 20-30% in all patients with acute myocardial infarction. Follow-up data of patients with either silent or anginal ischemia show a poor prognosis. Thus, all ischemic episodes occurring after myocardial infarction should be treated aggressively. Many multicenter studies have evaluated whether drug treatment can improve prognosis or protect from a nonfatal second attack. Calcium antagonists, especially those that increase heart rate, have not been considered as drugs of choice for this purpose, despite the many beneficial effects shown on myocardial tissue in experimental studies. In the study reported here, the effect of nisoldipine on postinfarction silent myocardial ischemia was evaluated by ambulatory left ventricular function monitoring. Ten patients were selected for study who showed silent myocardial ischemia after their first acute infarction. Blood pressure fell significantly (p < 0.05) after 4 weeks of treatment with nisoldipine (5-10 mg/day), but heart rate showed no change at rest. Exercise time improved (p < 0.05), with increased peak double products. During exercise, there was no significant change in end-diastolic volume but there was a marked improvement in end-systolic volume, and at the submaximal point the ejection fraction was significantly (p < 0.05) increased. Ejection fraction at rest also improved. The deterioration in ejection fraction due to dipyridamole was ameliorated by nisoldipine. Ejection fraction and blood pressure improved during the calculation test, and work performance also improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Animal model for evaluating the effect of systemic estrogen deficiency on residual ridge resorption.

The rate of resorption of residual ridges after tooth extraction varies among subjects. Despite many human studies, the etiologic factors of severe forms of resorption of residual ridges are unknown and probably multifactorial. To facilitate investigations of resorption of residual ridges, it is preferable to use an animal model with a dentoalveolar component similar to that of human beings. This study developed a rapid, nonhuman primate model in which one could measure resorption of residual ridges at the most critical period, with the least amount of time, minimal operation, and the least interference with normal nutrition. Three female Macaca fascicularis monkeys, 7 to 9 years old, were selected for simple extraction of four maxillary incisors, four mandibular incisors, and two mandibular canines. Lateral cephalographs were taken at weeks 0, 1, 2 to 3, 5 to 6, 8 to 9, 11 to 12, and 26 to 28 after extraction with a newly constructed cephalostat that allowed easy reproducibility of animal placement in the prone position. Height and area measurements were made of maxillary and mandibular anterior residual ridges in the superimposed cephalographs. Sequential mean bone loss data produced bone loss curves similar to those observed in humans. One animal underwent ovariectomy. The plasma levels of both estrogen and progesterone decreased over 25 days and stayed below the detection limits thereafter. Tooth extraction was done 4 weeks after the ovariectomy and the bone resorption pattern was able to be observed longitudinally with the newly established monkey cephalostat. The results indicated that Macaca fascicularis need not be sacrificed when used in longitudinal studies of resorption of residual ridges in a relatively short period of experimental time. This model can provide an excellent opportunity to investigate a causal relationship between the rate of resorption of residual ridges and predisposing systemic factors such as estrogen deficiency.

Alveolar Bone Loss↗

Epstein-Barr virus genome-positive tubulointerstitial nephritis associated with Kawasaki disease-like coronary aneurysms.

A patient with recurrent renal failure due to massive interstitial nephritis caused by Leu 3a + 3b-positive T-cell infiltration and associated with multiple thromboembolic attacks is reported. He died of gastrointestinal bleeding after treatment with anticancer agents. At autopsy, diffuse necrosis of the bilateral kidneys was noted as well as giant coronary aneurysms filled with thrombus that resembled those seen in Kawasaki disease and multiple old myocardial infarcts were also present. Among the various Epstein-Barr virus (EBV)-specific antibodies, the titers anti-viral capsid antigen (VCA) and anti-early antigen (EBEA) IgG antibody were always very high in contrast to the relatively low titers of anti-EB nuclear antigen (EBNA) antibodies. DNA extracted from kidney tissue obtained at autopsy was analyzed by Southern blot hybridization after the amplification of EBV-specific DNA by the polymerase chain reaction. In situ hybridization of kidney tissue obtained at biopsy was also performed using an enzyme-linked probe derived from the EBV-encoded RNA 1 (EBER1) gene. As a result, the EBV genome was found both at autopsy and in the biopsy tissue, which clearly revealed EBER1 in the interstitial cells. Taking account of the progressive ST-T changes of the electrocardiograms which were normal early in his course, multiple myocardial infarction associating multiple giant aneurysms probably occurred during this disease process. Thus, it could be concluded that chronic active EBV infection contributed massive interstitial nephritis mediated by the activation of Leu 3a + 3b-positive T cells.

Adult↗

The knife-edge tendency in mandibular residual ridges in women.

To investigate the bone resorption pattern of the residual alveolar bone, the morphologic change that occurred in mandibles was analyzed with standardized lateral cephalographs of 30 edentulous patients (15 women and 15 men). The longitudinal morphologic changes were measured at the sagittal sections of the mandibular bony contour at the symphysis area on superimposed cephalographic tracings. To quantify the morphologic change, a knife-edge index (KEI) was developed as the area change divided by the height change. Geometrically, the higher value of KEI represents the greater tendency to become a narrow residual ridge. The KEI values were statistically higher in the women than in the men (p less than 0.002). In addition, the value of KEI seems to correlate with osteopenic change at the center point of the body of the second vertebra (p less than 0.01). The continuous bone resorption activity in the edentulous mandible of women seems to be emphasized at the labial and lingual surfaces of the residual alveolar bone, resulting in a knife-edge type of residual ridge.

Absorptiometry, Photon↗

Lactate dehydrogenase isoenzymes in matrix vesicles (review).

Matrix vesicles (MV) isolated from mineralizing tissues contain high alkaline phosphatase (ALPase) activities associated with the membrane; this may be because MV originate from the plasma membrane of chondrocytes. Previous studies in our laboratory demonstrated that lactate dehydrogenase (LDH) isoenzymes, which appeared to be derived from chondrocytes cytosol, were located in MV of the epiphyseal growth plate of young-rabbit leg bones [1]. In the epiphyseal cartilage, alkaline phosphatase (ALPase) is enriched in the growth zone, whereas it is rarely detected in the resting zone, suggesting that MV containing ALPase are not present in the resting zone. In recent study, we divided the epiphyseal cartilages of young-rat rib bones into the growth zone and the resting zone, followed by the isolation of MV after collagenase digestion. MV containing ALPase and LDH were found in the growth zone, and surprisingly, vesicles containing LDH without ALPase were found in the resting zone [2]. The function of LDH-containing vesicles without ALPase is unknown at the present. However, these findings might accelerate the studies on cell-mediated calcification, because (1) LDH could be a marker enzyme of these vesicles, (2) LDH is found to be a specific cytosolic enzyme which is enfolded in these vesicles, suggesting that an unknown mechanism for the specific uptake of the cytosolic enzyme might be present.

Animals↗

Estrogen receptors, progesterone receptors and heat-shock 27-kD protein in liver biopsy specimens from patients with hepatitis B virus infection.

It has been proposed that in the human liver, the estrogen receptor gene may become inappropriately expressed as a consequence of HBV integration, contributing to cell transformation. This study was undertaken to examine estrogen receptor status in patients with hepatitis B virus infection and to analyze the expression of progesterone receptor and of a heat-shock 27,000-D protein (hsp27), both of which are estrogen regulated in estrogen target tissues. Receptor proteins were detected in liver biopsy specimens by immunocytochemistry using antireceptor monoclonal antibodies; a monoclonal antibody was also used to detect hsp27. Estrogen receptor and progesterone receptor were mainly seen in the nuclei of hepatocytes. The presence of hepatitis B virus infection did not always result in elevated estrogen receptor expression, but in general the expression of this receptor protein was higher in hepatitis B virus-positive patients than in patients with the same pathological findings (hepatitis, cirrhosis, hepatocarcinoma) but without hepatitis B virus. This was more clearly seen in the patients with hepatitis. Although estrogen receptor expression was moderate to high in many samples, the expression of the two biochemical markers of estrogen action at postreceptor levels (progesterone receptor and hsp27) was low or absent in most of the liver tissues examined, suggesting that in the liver the interaction of estrogen-estrogen receptor-DNA has characteristics inherent to this tissue.

Adolescent↗

Vesicles with lactate dehydrogenase and without alkaline phosphatase present in the resting zone of epiphyseal cartilage.

Matrix vesicles are membrane-invested vesicles that initiate mineralization in the extracellular matrix of calcifying tissues. The epiphyseal cartilages of young-rat rib bones were divided into the growth zone and the resting zone, followed by the isolation of matrix vesicles after collagenase treatment. Matrix vesicles with both alkaline phosphatase and lactate dehydrogenase were detected in the growth cartilage found in the epiphyseal growth plates of young rabbits [Hosokawa, Uchida, Fujiwara & Noguchi (1988) J. Biol. Chem. 263, 10045-10047], but were not detected in the resting zone. By contrast, and surprisingly, lactate dehydrogenase-containing vesicles without alkaline phosphatase were found in the resting zone, but not in the growth zone. In both the growth and resting zones, isoenzyme patterns of lactate dehydrogenase in the two different vesicles were identical with those of cytosolic lactate dehydrogenase of chondrocytes, suggesting the presence of a mechanism for specific uptake of cytosolic lactate dehydrogenase. The same results as for young-rat rib bones were obtained with the resting and growth cartilages of young-dog and monkey rib bones.

Alkaline Phosphatase↗

Lactate dehydrogenase isoenzymes are present in matrix vesicles.

Matrix vesicles were isolated from epiphyseal growth plates of young rabbits. Lactate dehydrogenase activity was detected in the isolated matrix vesicles only in the presence of detergents, suggesting that NADH, the cofactor for the assay, does not penetrate the membrane of matrix vesicles. In contrast, the activity of alkaline phosphatase, a marker enzyme of the outer surface of matrix vesicles, was detected in the matrix vesicles using p-nitrophenyl phosphate as the substrate both in the presence and absence of detergents. Lactate dehydrogenase activity was detected only in the cytosol of chondrocytes of the epiphyseal growth plates but not in other subcellular fractions, showing that lactate dehydrogenase is not from the plasma membrane and membranes of intracellular organelles of chondrocytes. The isolated matrix vesicles contained all five lactate dehydrogenase isoenzymes but did not possess other cytosolic enzymes. These results show that lactate dehydrogenase is located in the matrix vesicles and suggest the presence of a mechanism for the specific uptake of cytosolic lactate dehydrogenase and the possibility of enzymatic quantification of the matrix vesicles at various calcification sites.

Animals↗

Evaluation of myocardial infarct size in rat heart by pinhole SPECT.

BACKGROUND: High-resolution single photon emission computed tomography (SPECT) with a pinhole collimator is a new method for evaluating the regional properties of radiopharmaceuticals in small laboratory animals in vivo. Although several reports of normal images of rat taken by this new technique are available, there are as yet few reports on its use in disease models, such as myocardial infarction. In this study, we clearly visualized myocardial flow in the rat heart with myocardial infarction using this system, and evaluated the relationship between SPECT images and histologic analysis. METHODS AND RESULTS: For visualization of myocardial flow in rat heart, 201Tl images were taken just before and 24 days after left coronary artery ligation. The images were taken using a 4-head SPECT scanner with pinhole collimators. The percent infarct size on 201Tl-SPECT imaging (%SI) and the defect score were then assessed and compared with the percent infarct size on histologic analysis (%HI). Both the %SI and defect score correlated well with %HI (r = 0.97 and 0.74, respectively). CONCLUSION: Serial SPECT imaging using pinhole collimators permits estimates of myocardial flow even in small laboratory animals noninvasively in vivo.

Animals↗

The effects of buccolingual width and position of occlusal rest seats on load transmission to the abutments for tooth-supported removable partial dentures.

PURPOSE: The suitable buccolingual width and the location of occlusal rest seats for removable partial dentures have not been scientifically established. The aim of the present study was to use three-dimensional geometric analysis to evaluate the effects of buccolingual width and the location of occlusal rest seats on load transmission to the abutments for tooth-supported removable partial dentures. MATERIALS AND METHODS: A tooth-supported portion of a maxillary removable partial denture with two conventional circumferential cast clasps and an indirect retainer was analyzed. Occlusal loading of 100 N was applied to the buccal mesial cuspal incline 2.0 mm from the central fossa of the first molar or to the lingual mesial cuspal tip. Four combinations of position and width (wide, buccal shift, middle, and lingual shift) were simulated. RESULTS: For buccal loading, the wide rests and buccal-shift rests produced lower tensile forces at the indirect retainer. For lingual loading, the buccal-shift rests produced the lowest compressive force to the anterior abutment. CONCLUSION: Based on the tooth-supported removable partial dentures that were analyzed, buccal shifting of the rest seats seems to be advantageous for load transmission to the abutments.

Bicuspid↗