[Imaging of cardiac blood pool].
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Biomedical subjects
Publications and source records attributed to M Hosono.
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Severe esophageal compression due to a vascular ring rarely develops after childhood. We report a case of a 35-year-old man with dysphagia associated with a vascular ring. Radionuclide transit studies were performed before and after surgery for quantitative evaluation of deglutition. Preoperative aortogram disclosed a right sided aortic arch and a retroesophageal left subclavian artery arising from a diverticulum of the arch. Because of the severity of his symptoms, he was taken to surgery. He underwent posterolateral thoracotomy through the fourth intercostal space and division of the ligamentum arteriosum. The esophagus was mobilized from the aortic arch, the arch diverticulum, the pulmonary artery, and the trachea. Postoperatively, he experienced immediate resolution of dysphagia and quickly began eating a regular diet. Although a postoperative esophagogram revealed the esophageal compression, esophageal scintigraphy using 185 MBq 99mTc pertechnetate revealed shortening of the transit time of swallowed water by 1.0 second after surgery. Quantitative evaluation of deglutition in the esophagus by scintigraphy was useful for this patient, since he suffered from psychiatric problems.
The changes in the T cell repertoire of aging BALB/c mice include an increase of V beta 8 + T cells, most of which have a relatively low density of T cell receptors (TCR). We investigated the response of V beta 8 + T cells to staphylococcal enterotoxin B (SEB), a superantigen from a common bacterium, the anamnestic response to which is thought usually to be part of the defense against infection. The injection of an amount of SEB optimum for V beta 8 + T cell proliferation in young mice induced little or no proliferative response in aged mice, and within one or two days they died in shock with apoptotic cells in the spleen, a sign of T cell-shock caused by SEB. Flowcytometry analysis (FCA) 15 h after SEB injection, when cell division had not yet started, revealed the loss of 90% of V beta 8 + T cells in the blood and of 50% in the spleen in mice of all ages tested. However, conspicuous in the remaining V beta 8 + T cells in the spleens of the young mice but not in those of the aged mice, was an increased cellular complexity, as shown by the fact that light was strongly side scattered in FCA, indicating intracellular re-organization. The remaining T cells in the young could include progenitors for the expanding population of V beta 8 + T cells. As seen in lethal shock, V beta 8 + T cells in the aged are not unresponsive to SEB in vitro. They responded to the antigen by increasing the amount of TCR up to the level of that in young mice, but without proliferation. The proliferation arrest of V beta 8 + T cells of aged mice was found to be an intrinsic defect in in vitro cell mixture experiments, in which they were cocultured with young spleen cells which provided a complete immune microenvironment. It was simultaneously found in vitro that most of the V beta 8 + T cells from aged mice disappeared after antigen stimulation and that their disappearance was prevented by the presence of spleen cells from young mice, although they still did not proliferate. Taken all together the findings suggest that V beta 8+ T cells in the aged are at the end state of maturation and terminate by apoptotic death, causing T-cell shock in response to SEB.
Radiographic, computed tomographic and scintigraphic findings of a patient with separated, multilocular periosteal ganglion are reported. Multiple periosteal cystic masses with calcification in small parts of the cyst walls were demonstrated in the surface of the left tibia by plain radiograms and CT. The accumulations of technetium-99m hydroxymethylene diphosphonate and pentavalent technetium-99m dimercaptosuccinic acid were shown in the calcification in the periosteum and wall of the cyst. Needle puncture revealed that the masses were filled with jelly-like fluid. The masses were diagnosed as multiple ganglionic cysts at the periosteum of the left tibia.
A specific gas chromatography/mass spectroscopy method with a detection limit of 0.1 ng/mL was developed for the measurement of 6-(3-dimethylaminopropionyl)forskolin (1) in beagle plasma. Using this method, plasma concentrations of 1 in beagles given pharmacologically effective intravenous doses of 1.HCl were determined. The observed maximal plasma concentrations rapidly decreased with time, and half-lives of the alpha-phases were < 9 min. Pharmacological effects of 1 on the cardiovascular parameters were simultaneously evaluated in one of the studies. Decreases of the pharmacological effects were slower than decreases in plasma concentration of 1. In addition, 6-(3-methylaminopropionyl)forskolin (N-monodemethyl 1), an expected initial metabolite of 1, was prepared and found to be as pharmacologically active as 1 in beagles. These results and others strongly suggest that a metabolite(s) of 1 contributes to the pharmacological effects of 1 in beagles.
The murine monoclonal antibody (mAb) 145-9 recognizes an epitope present on CA125 but different from the epitope defined by the mAb OC125. To evaluate the clinical usefulness of the 145-9 antibody, immunoscintigraphy was performed in ovarian cancer patients and the effect of circulating CA125 on tumor imaging was investigated. Two milligrams (74 MBq) of 111In-labeled 145-9 was injected intravenously into 11 patients with ovarian cancer. Pre-injection serum CA125 concentrations were between 166 U/ml and 7414 U/ml. Tumors were visualized in 10 of 11 patients. In two patients, lymph nodes that were not detected by other imaging modalities but were clinically suspected as metastases were visualized. There was no correlation between serum CA125 level and antibody uptake in the tumors. Immune complexes between the antibody and circulating antigen were observed in sera of all the patients, but the fraction of radioactivity in complex form did not correlate well with serum CA125 levels. The immune complexes survived in the circulation and the circulating radiolabel, including immune complexes, was still bound to solid-phase CA125. The plasma clearance rate and hepatic uptake of the antibody were not significantly affected by circulating CA125. In conclusion, the antibody 145-9 formed complexes with CA125 in vivo but this did not Compromise the outcome of antibody imaging. The antibody 145-9 can be used in immunoscintigraphy of ovarian cancer irrespective of serum CA125 level.
We examined the potential of radiolabeled somatostatin analogs, 125I-Tyr-3-octreotide (125I-octreotide), (111)In-DTPA(diethylenetriaminepentaacetatic acid)-D-Phe-1-octreotide (111In-octreotide), and 188Re-octreotide for targeting small-cell lung cancer (SCLC) in a mouse model. Tyr-3-octreotide was labeled with 125I by the chloramine T method, and (111)In-octreotide was obtained as a kit, while 188Re was eluted from a 188W/188Re generator, and octreotide was directly labeled with 188Re by reducing disulfide bonds. The 125I-, 111In-, and 188Re-octreotides were injected i.v. into athymic mice bearing NCI-H69 tumors, and the biodistributions were determined at 15 min, and 2, 4, 8, and 24 h. Tumor uptakes were 0.5+/-0.2, 0.3+/-0.1, 0.3+/-0.1 %ID/g, and tumor-to-blood ratios were 1.8, 11.9, 1.2 at 8 h for 125I-, 111In-, and 188Re-octreotides, respectively. Accumulations of 111In-octreotide in normal tissues were lower than those of 125I- and 188Re-octreotides. 188Re-octreotide can be used to localize SCLC lesions as efficiently as radioiodinated octreotide. However, 111In-octreotide was the most suitable agent to obtain high tumor-to-normal tissue contrast for localizing SCLC.
Water-soluble forskolin and 7-deacetylforskolin derivatives with an aminoacetyl, a 3-aminopropionyl, or a 4-aminobutyryl group at the 6- or 7-position were prepared, and their positive inotropic as well as vasodilative activities were evaluated in anesthetized dogs. 7-Deacetylforskolin (2) and 7-deacetyl-1-silylforskolin (6) were converted to the corresponding 7-chloroacylderivatives (3, 7, 10), which were reacted with amines to obtain 7-aminoacyl-7-deacetylforskolins (4a-f, 9a, b, 11). The 7-acyl substituents migrated to the 6-position with sodium hydroxide in acetonitrile-water to afford 6-aminoacyl-7-deacetylforskolins (12a-f). The 7-position of 12a, d-f was selectively acetylated with acetyl chloride to obtain the corresponding 6-aminoacylforskolins (13a-d). Among the 6-aminoacylforskolins, 6-(3-dimethylaminopropionyl)forskolin (13b) and 6-(4-dimethylaminobutyryl)forskolin (13d) exhibited potent positive inotropic and vasodilative activities comparable to those of forskolin (1). The activities of 13b and 13d were approximately ten times more potent than those of 7-aminoacyl- and 6-aminoacyl-7-deacetylforskolins (4a-f, 9a, 12a-c, f). 6-Dimethylaminoacetylforskolin (13a) and 6-(3-diethylaminopropionyl)forskolin (13c) were less potent than 1. The effects of the soluble forskolins on adenylate cyclase activity were also examined in vitro. 6-Aminoacylforskolins (13a-d) exhibited potent adenylate cyclase-stimulating activity, comparable to that of 1.
Effect of cilnidipine (CIL) on renal function in SHR were evaluated in comparison with that of nifedipine (NIF) and nicardipine (NIC). In conscious SHR, CIL (3 and 10 mg/kg, p.o.) increased the urine volume, urinary Na+ excretion and urinary Na+/K+ ratio. NIF (3 and 10 mg/kg, p.o.) and NIC (10 mg/kg, p.o.) also increased the urine volume and urinary Na+ excretion, but not the urinary Na+/K+ ratio. In anesthetized SHR, CIL (3 and 10 micrograms/kg, i.v.) and NIF (10 micrograms/kg, i.v.) elevated the renal blood flow (RBF), but NIC did not. CIL (10 micrograms/kg, i.v.) also increased the glomerular filtration rate (GFR), whereas NIF did not. Furthermore, we investigated the effect of these three drugs on endothelin (ET)-induced renal dysfunction in anesthetized SHR. ET (2 micrograms/kg, i.v. +30 ng/kg/min) prolongly reduced RBF, GFR and urine volume by 47, 60 and 48%, respectively. CIL (1-10 micrograms/kg, i.v.) improved the decrease in RBF and urine volume induced by ET as well as NIF and NIC. When blood pressure was lowered to the similar extent among the three drugs in ET-treated SHR, CIL increased the RBF and urine volume compared with the others. NIF and NIC did not affect the reduction in GFR by ET, but CIL (0.3-3 micrograms/kg, i.v.) significantly increased GFR. These results suggest that CIL, NIF and NIC all have natriuretic action and no suppressive action on renal function in SHR. In addition, CIL has an ameliorative effect on renal dysfunction in ET-treated SHR, suggesting that CIL might improve renal dysfunction not only in hypertensive patients but also in those with acute renal failure.
Effects of prolonged noradrenaline infusion on the density of cardiac beta-adrenoceptors, phosphodiesterase (PDE) and adenylate cyclase (AC) activities, and the ability of NKH477, 6-(3-dimethylaminopropionyl) forskolin hydrochloride, to increase tension development and heart rate were studied in rat cardiac preparations. Noradrenaline infusion (400 micrograms/kg/hr, s.c.) for 7 days significantly decreased cardiac beta-adrenoceptor density (Bmax), whereas the binding affinity (Kd) of the ligand was unchanged. The basal cardiac PDE activity was increased in treated rats, whereas there was no difference in the basal cardiac AC activity between treated and untreated rats. Significant decreases in basal developed tension and heart rate were observed in the left and right atrial muscles from treated rats, respectively. The positive inotropic and chronotropic potencies of NKH477 were unaffected by noradrenaline infusion, whereas the positive inotropic potencies of isoproterenol and 3-isobutyl-1-methylxanthine were significantly reduced. Thus, NKH477 appears to be superior to beta-adrenoceptor agnosits or PDE inhibitors as a cardiotonic drug in the treatment of heart failure accompanied by beta-adrenoceptor downregulation.
Catalase (CAT) is an enzyme to scavenge H2O2 and to protect peroxidation of cell wall lipid and lipoproteins. The increase in its activity has been observed in several diseases as an compensating reaction. The decrease in its activity may be related to some pathophysiologies of diseases. However, there has been few reports on the measurement of serum CAT activity. We formerly reported the method to measure CAT accurately with an automated analyzer. In the present experiment, we measured CAT in various kinds of diseases and healthy controls by this method. By an analysis of serum samples which were obtained from randomly selected 1,051 patients at Chibune Hospital for 12 months (from January to December, 1993), we obtained following results. The CAT of neuromuscular, cardiovascular and metabolic diseases were significantly high (p < 0.01). The CAT of psychiatric and otorhinopharyngologic diseases were significantly low (p < 0.01). There was significant relationship between CAT and some biochemical markers. CAT is thought as a protector against tissue injuries or circulatory insufficiencies. These results indicate that CAT increases in some kinds of diseases as a protection reaction to the injury, and that the decrease of CAT may cause some kinds of diseases.
A successful closure of patent ductus arteriosus (PDA) in a 70-year-old women is described. The patient had poor pulmonary function and calcification of the aortic arch and the descending aorta, as well as arteriosclerosis obliterans bilaterally in the iliac arteries. We therefore performed trans-pulmonary artery direct closure of the ductus arteriosus via a median strenotomy. In surgery, we used a Foley balloon catheter inserted into the aorta through the ductus to prevent backflow. Leakage of blood from the ductus, even with use of balloon occlusion, required the reduction of perfusion flow to 500 ml/min and temporary circulatory arrest. Rectal temperature was 27 degrees C when the aorta was cross-clamped. The ductus orifice was primarily closed with three mattress sutures with pledgets, and this sutured orifice was secondarily covered with a bovine pericardial patch. The postoperative course was satisfactory. Trans-pulmonary artery direct closure of the PDA using cardiopulmonary bypass is useful for aged patients. This patient is, as far as our knowledge, the oldest surgical report in Japan.
Physiological changes with increasing age are generally accompanied by disorders of immunity, including autoaggression which can be seen in some syngeneic host-versus-graft reactions provoked when responder and stimulator cells are of different ages. The magnitude of the response, however, varies with the strain of mice. Footpad injection of irradiated spleen cells from 1-year-old, but not from 2-month-old, BALB/c mice (H-2d) into syngeneic young mice evoked popliteal lymph node-swelling, but this was not the case in DBA/2 (H-2d) mice. Therefore, the generation of autoreactivity was thought to be closely related to the change of T cell repertoire with age in the former strain of mice. At around 1 year of age, when only a small reduction in T cell number was observed and when a slight increase in CD8+ T cells in the periphery caused the CD4/CD8 ratio to be lower than in young mice, the proportion of V beta 8+ cells in BALB/c mice started to increase, increasing from 16% in the young to 27% in 2-year-old mice (P < 0.01). On the other hand, V beta 6+ T cells remained at the same level as in young mice throughout life. The increasing fraction of V beta 8+ T cells was characterized by a low density of T cell receptors (TcR) and it was more conspicuous in the spleen than in the peripheral blood in mice more than 1 year of age. A shift to a TcR-low population in V beta 8+, T cells was followed in a few months by a shift in V beta 6+ T cells. Although both the change of T cell repertoire and development of autoaggression may be parameters of aging, no direct correlation was demonstrated between them in experiments with cross-hybrids and recombinant inbred strains of BALB/c and DBA/2 mice. Probably, the two parameters are genetically and independently controlled. All the data taken together indicate that T cells undergo V beta-TcR-restricted changes during their life history, depending on their genetic background.
A murine monoclonal antibody MLS102 recognizes sialosyl-Tn antigen in mucin and immunohistochemically reacts with more than 80% of colorectal cancer tissues. The purpose of this study was to assess the usefulness of this monoclonal antibody for the immunoscintigraphy of colorectal cancer. Planar and SPECT images were obtained on day 2 or day 3 after injection of 2 mg and 74 MBq 111In-labeled MLS102 antibody into 17 patients with colorectal cancer. Nine of 11 primary tumors and 4 of 6 locally recurrent tumors were detected. Positive images were obtained in all tumors larger than 4.5 x 2.7 cm. Three tumors of less than 2.5 cm and 1 recurrent tumor, which was missed by other imaging modalities, were negative. There were no adverse reactions. Human anti-(mouse Ig) antibody developed in 4 patients. Although improvement of detectability for smaller tumors needs to be pursued, the antibody MLS102 is potentially promising for use in immunoscintigraphy of colorectal cancer.
We reported two Tc-99m(V) DMSA scintigrams in patients with idiopathic synovial chondromatosis which affected the metacarpo-phalangeal joint and shoulder joint. Tc-99m(V) DMSA accumulated markedly and diffusely in the tumor. Tc-99m(V) DMSA scintigraphy would be valuable for deciding the optimal site for biopsy.
It is sometimes difficult to understand the three-dimensional (3D) relationship of cardiac and mediastinal structures despite advances in magnetic resonance (MR) imaging techniques. We present a low-cost system for 3D reconstruction of the major mediastinal structures by processing the MR imaging data on a NeXT workstation. MR images of multisection, multiphase, spin-echo techniques stored in a picture archiving and communication system (PACS) data base were used for the reconstruction. The computer program obtained the contours of the multiple components of the mediastinal structures by the combination of automatic and manual procedure. The bundled software of a 3D kit was used for surface rendering of hidden surface removal, shading of the visible parts of the surfaces, perspective transformation, and motion parallax by rotation of the surfaces. 3D reconstruction was performed in 15 patients with cardiac diseases, and the 3D-reconstructed images were compared with the plain chest x rays of the patients. The 3D presentation clearly showed the complex anatomy of cardiovascular diseases and helped elucidate the misconceptions in the interpretation of the plain chest x rays. Our 3D images are used for education and should be viewed by medical students and beginners in radiology at an individual pace with plain chest radiographs, MR images, and legends. Although applied to the heart and the great vessels in this report, this system is also applicable to other structures.
To experimentally assess the kinetics of platelets in thrombocytopenia, we constructed a canine model using 111In-oxine labeled autologous platelets and an intact antiplatelet monoclonal antibody (MAb) NNKY2-11 (IgG2a). With the infusion of radiolabeled autologous platelets into dogs, the peripheral platelet count and blood radioactivity level were examined, and the radioactivity in the liver, spleen and heart was determined with scintigraphic analysis. Thereafter, i.v. injection of 100 micrograms/kg of NNKY2-11 had no effect on platelet counts or the biodistribution of radiolabeled platelets. However, 200 and 300 micrograms/kg of MAb reduced the platelets, and the radioactivity of the liver and spleen augmented clearly after injection of MAb. Platelet radioactivity in serum, which had decreased after MAb infusion, did not recover, even when peripheral platelet counts returned to the normal levels, indicating that these new platelets might be derived from the platelet-storage pool or new thrombocytogenesis. This model of antiplatelet MAb induced thrombocytopenia seems to be useful for analyzing the kinetics of platelets in thrombocytopenia.