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Biomedical subjects

S Umeda

Publications and source records attributed to S Umeda.

At least 37 records · Page 2Linked to original sources

Macrophage differentiation and granulomatous inflammation in osteopetrotic mice (op/op) defective in the production of CSF-1.

Since the osteopetrotic (op/op) mouse was demonstrated to have a mutation within the coding region of the CSF-1 gene itself, it serves as a model for investigating the differentiation mechanism of macrophage populations in the absence of functional CSF-1. The op/op mice were severely monocytopenic and showed marked reduction and abnormal differentiation of tissue macrophages. Osteoclasts as well as marginal metallophilic macrophages and marginal zone macrophages in the spleen were absent. Most of the tissue macrophages were reduced in number and ultrastructurally immature. However, the degree of reduction in numbers of macrophages in the mutant mice was variable among tissues, suggesting that the heterogeneity of macrophages was generated by their different dependency on CSF-1. After daily CSF-1 injection, the numbers of monocytes, tissue macrophages, and osteoclasts were remarkably increased, and the macrophages showed morphological maturation. However, the numbers of macrophages in the ovary, uterus, and synovial membrane were not increased. In the bone marrow, macrophage precursors detected by monoclonal antibody ER-MP58 proliferated and differentiated into preosteoclasts and osteoclasts. In the spleen, marginal metallophilic macrophages and marginal zone macrophages developed slowly. In this manner, CSF-1 plays an important role in the development, proliferation, and differentiation of certain tissue macrophage populations and osteoclasts. In the op/op mice, Kupffer cells proliferated, transformed into epithelioid cells and multinucleated giant cells, and participated in glucan-induced granuloma formation. In CSF-1-treated op/op mice, the process of granuloma formation was similar to that in normal littermates due to increased monocytopoiesis and monocyte influx into the granulomas. These results indicate that CSF-1 is a potent inducer of the development and differentiation of CSF-1-dependent monocyte/macrophages, and that CSF-1-independent macrophages also play an important role in granuloma formation.

Animals↗

Radical cystectomy using endoscopic stapling devices: preliminary experience with a simple and reliable technique.

PURPOSE: We introduce a new technique to decrease operative time and blood loss during radical cystectomy. MATERIALS AND METHODS: We used endoscopic stapling devices for secure hemostasis, as well as rapid division of the bladder and prostatic lateral ligaments, and the deep dorsal vein complex during radical cystectomy in 16 patients with bladder or urethral cancer compared to 11 who underwent cystectomy via a conventional method, consisting of incision and ligation with sutures. RESULTS: In most cases the endoscopic staplers were useful for sufficient hemostasis and rapid division of the ligaments and/or venous plexus. Mean total operative time with the stapling technique was significantly shorter than that with the standard technique (p = 0.003), and mean total blood loss was less than with the standard technique but the difference was not statistically significant. CONCLUSIONS: Although our study was not designed in a randomized manner, we believe that endoscopic stapling devices facilitate radical cystectomy.

Blood Loss, Surgical↗

Development, differentiation, and phenotypic heterogeneity of murine tissue macrophages.

In murine ontogeny, macrophage precursor cells develop in the yolk sac and fetal liver. Primitive macrophages also appear in the yolk sac, migrate to various tissues, and differentiate into several fetal macrophage populations. Because the development of the monocytic cell lineage is incomplete in the early stage of fetal hematopoiesis, primitive/fetal macrophages are considered to originate from granulocyte-macrophage colony forming cells or earlier macrophage precursors, bypassing the early monocytic cell series. In adult mice rendered severely monocytopenic by administration of strontium-89, resident macrophages are maintained by self-renewal. In contrast, administration of liposome-encapsulated dichloromethylene diphosphonate (clodronate) results in the elimination of various tissue macrophage populations. The repopulation of affected macrophages is dependent on the increase of precursors in the liver and spleen during the period of macrophage depletion. Such precursors reconstitute heterogeneous macrophage subpopulations. In mice homozygous for the osteopetrosis (op) mutation, the absence of macrophage colony-stimulating factor (M-CSF) activity results in a deficiency of monocytes and monocyte-derived macrophages. However, immature macrophages are present in various tissues. Administration of M-CSF to op/op mice induces the increased proliferative capacity and the morphological maturation of macrophages. However, the responses of individual tissue macrophage subpopulations to M-CSF are different. These results indicate that macrophage development, differentiation, and proliferation are regulated by the tissue microenvironment including the in situ production of macrophage growth factors in both fetal and adult life.

Animals↗

Lymphocyte activation effect of (1-->6)-2,5-anhydro-D-glucitol and it derivatives with 3,4-di-O-methyl and sulfate groups.

(1-->6)-2,5-Anhydro-3,4-di-O-methyl-D-glucitol (2a) and (1-->6)-2,5-anhydro-D-glucitol (2c) and its sulfated derivative (2d) were synthesized and their biological activities were evaluated in regards to the effects on murine lymphocytes. The polymers showed different effects on the lymphocytes depending on the substituent groups. The sulfated polymer (2d) induced mitogenic activities, and specifically activated the CD4(-)CD8(-) subset of lymphocytes.

Animals↗

[Extracorporeal shock wave lithotripsy for ureteral stone using a piezoelectric lithotriptor--usefulness of treatment on an outpatient clinic].

PURPOSE: We have clarified the usefulness of extracorporeal shock wave lithotripsy for patients with ureteral stone in an outpatient clinic. PATIENTS AND METHOD: One hundred ten patients with ureteral stone were treated using a small focused piezoelectric lithotriptor (Toshiba ESL-500A). No anesthesia and no associated therapy was applied to all patients. RESULTS: Ninety eight patients (89.1%) were successfully treated in our outpatient clinic. Twelve patients (10.1%) were treated after admission because of several reasons such as colicky attack. In 107 patients (97.3%) no remaining stone was observed. We judged our treatment was effective in 109 patients (99.1%) including 2 cases with very small remaining fragment. No serious complication was encountered. In 83 cases with ureteral stone smaller than 10 mm in longer diameter, mean treatment sessions was 1.24 and mean total shots was 3,227. In contrast, in 27 cases with ureteral stone bigger than 10 mm, mean 2.67 sessions and 11,715 shots was needed. Although some patients with bigger stone underwent several sessions up to 9 times, all of them had no problem before completion of treatment. CONCLUSION: These results indicated that most of patients with ureteral stone can be simply treated in an outpatient clinic using a small focused piezoelectric lithotriptor.

Adolescent↗

Effects of macrophage colony-stimulating factor on macrophages and their related cell populations in the osteopetrosis mouse defective in production of functional macrophage colony-stimulating factor protein.

The development of macrophage populations in osteopetrosis (op) mutant mice defective in production of functional macrophage colony-stimulating factor (M-CSF) and the response of these cell populations to exogenous M-CSF were used to classify macrophages into four groups: 1) monocytes, monocyte-derived macrophages, and osteoclasts, 2) MOMA-1-positive macrophages, 3) ER-TR9-positive macrophages, and 4) immature tissue macrophages. Monocytes, monocyte-derived macrophages, osteoclasts in bone, microglia in brain, synovial A cells, and MOMA-1- or ER-TR9-positive macrophages were deficient in op/op mice. The former three populations expanded to normal levels in op/op mice after daily M-CSF administration, indicating that they are developed and differentiated due to the effect of M-CSF supplied humorally. In contrast, the other cells did not respond or very slightly responded to M-CSF, and their development seems due to either M-CSF produced in situ or expression of receptor for M-CSF. Macrophages present in tissues of the mutant mice were immature and appear to be regulated by either granulocyte/macrophage colony-stimulating factor and/or interleukin-3 produced in situ or receptor expression. Northern blot analysis revealed different expressions of GM-CSF and IL-3 mRNA in various tissues of the op/op mice. However, granulocyte/macrophage colony-stimulating factor and interleukin-3 in serum were not detected by enzyme-linked immunosorbent assay. The immature macrophages differentiated and matured into resident macrophages after M-CSF administration, and some of these cells proliferated in response to M-CSF.

Animals↗

Pathomechanism of spontaneous regression of the herniated lumbar disc: histologic and immunohistochemical study.

To ascertain the pathomechanism of spontaneous regression of lumbar disc herniation, histological and immunohistochemical studies on 100 herniated discs were performed. Inflammatory findings such as cell infiltration, neovascularization, and granulation were observed in 16.9% of the protruded discs, 81.8% of the subligamentously extruded discs, 100% of the transligamentously extruded disks, and 80% of the sequestrated discs. The infiltrated cells were composed mainly of macrophages and a small number of T lymphocytes. Furthermore, the cell infiltration was more prominent in the nucleus pulposus (NP) than in the annulus fibrosus (AF). There was no correlation between the occurrence rate of inflammatory response and the length of the period from onset to operation. Based on these findings, it is considered that an extruded or sequestrated disc has a potential to be resorbed by phagocytes.

Adolescent↗

Neonatal changes of osteoclasts in osteopetrosis (op/op) mice defective in production of functional macrophage colony-stimulating factor (M-CSF) protein and effects of M-CSF on osteoclast development and differentiation.

In mice homozygous for the osteopetrosis (op) mutation, loss of osteoclasts in the postnatal period and their development, differentiation, and maturation following daily M-CSF administration in adult life were investigated. Histochemical, immunohistochemical, and ultrastructural approaches, as well as [3H]thymidine autoradiography, clarified the role of M-CSF on osteoclast development and differentiation. In op/op mice osteoclasts appeared normal at birth. However, osteoclast numbers were reduced within a few days after birth, and osteoclasts were undetectable by 3-4 days of age. In adult op/op mice there were no multinuclear osteoclasts; however, small numbers of mononuclear cells (so-called 'preosteoclasts') were observed on the endosteal surface of bone. These preosteoclasts expressed tartrate-resistant acid phosphatase and showed ultrastructural features of immature osteoclasts. After daily M-CSF administration in op/op mice, osteoclasts developed from the fusion of preosteoclasts and osteoclasts numbers increased to the levels of normal littermates at 3 days. Autoradiographic analysis with [3H]thymidine revealed no labeling in osteoclasts and preosteoclasts. In the mutant mice, M-CSF administration induced numerical increases of monocytes, promonocytes, and earlier precursor cells in bone marrow, ER-MP12- or, ER-MP58-positive granulocyte/macrophage colony-forming cells (GM-CFCs). Among these macrophage precursors, ER-MP58-positive cells were considered preosteoclast precursors, and possessed marked proliferative potential. These data suggest that an ER-MP58-positive cell subpopulation of GM-CFCs proliferates in response to M-CSF, differentiates into preosteoclasts which fuse with each other to develop into mature osteoclasts.

Animals↗

Macromolecular ionophores. 1. Chiral recognition properties of poly[(1-->6)-2,5-anhydro-D-glucitol] toward racemic amino acid ester.

The chiral recognition property of poly[(1-->6)-2,5-anhydro-3,4-di-O-alkyl-D-glucitol] (1) toward racemic RCH (CO2CH3)NH3+.PF6- (2.HPF6) has been studied using a transport system involving an aqueous source and receiving phases separated by a chloroform phase containing 1. Transport rates for aromatic guests 2a (R = Ph) and 2b (R = CH2Ph) were faster than those for aliphatic guests, 2c (R = CH(CH3)2) and 2d (R = CH2CH(CH3)2), using the polymer substituted with methyl groups (1a). The enantiomeric excess (e.e.) was 10.9% for 2a as a maximum value and decreased in the order of 2a > 2c > 2b = 2d. When the transport of 2a.HPF6 was carried out using the polymers with 3,4-di-O-methyl (1a), ethyl (1b), allyl (1c), and pentyl (1d) groups, the e.e. was 22.0% for 1d as a maximum value and increased in the order of 1a < 1b < 1c < 1d. The formation of a complex between 1a and 2a.HPF6 was confirmed by 1H and 13C NMR spectral measurements.

Amino Acids↗

Symptomatic arachnoiditis ossificans of the thoracic spine. Case report.

This report describes a man aged 65 years who developed spastic paraparesis secondary to arachnoiditis ossificans in the thoracic spine. Over 35 years previously, in Southeast Asia, the patient had received repeated lumbar punctures in the treatment of meningitis possibly associated with malarial fever. He had multiple arachnoidal ossifications located at levels from T6 to T9 dorsal to the spinal cord which were well delineated by computed tomography. The lesions were completely extirpated by dorsal route surgery, and the patient had marked neurological improvement after surgery. Histology confirmed that the lesions showed mature bone that formed with an osseous marrow and trabeculae, and the lesions exhibited clusters of arachnoidal cells as well as the proliferation of osteoblasts surrounding the ossified area. Early diagnosis and surgical intervention, however, are mandatory in such cases, if the patient is to attain an acceptable degree of recovery.

Aged↗

Effects of macrophage colony-stimulating factor (M-CSF) on the development, differentiation, and maturation of marginal metallophilic macrophages and marginal zone macrophages in the spleen of osteopetrosis (op) mutant mice lacking functional M-CSF activity.

Immunohistochemical techniques using an anti-mouse panmacrophage monoclonal antibody and anti-mouse monoclonal antibodies specific for marginal metallophilic macrophages or marginal zone macrophages were used to detect red pulp macrophages, marginal metallophilic macrophages, and marginal zone macrophages in the spleen of op/op mice. In the mutant mice, the red pulp macrophages were reduced to about 60% of those in the normal littermates and the marginal metallophilic macrophages and marginal zone macrophages were absent. After administration of recombinant human macrophage colony-stimulating factor (rhM-CSF), numbers of red pulp macrophages increased rapidly, reaching levels found in normal littermates 1 week later. In contrast, the marginal metallophilic macrophages as well as the marginal zone macrophages appeared slowly after rhM-CSF administration and their numbers were less than half of the baseline level of normal littermates even at 12 weeks of administration. The distribution of marginal metallophilic macrophages and marginal zone macrophages appearing after M-CSF administration was irregular in the spleen of the op/op mice. These splenic macrophage subpopulations differed in their responses to rhM-CSF, suggesting that distinct mechanisms may be involved in their development and differentiation. The splenic red pulp macrophages present in unmanipulated op/op mice are an M-CSF-independent macrophage population. Although the marginal metallophilic macrophages and marginal zone macrophages are thought to be M-CSF-dependent, their development and differentiation appear to be influenced by locally produced M-CSF or other cytokines.

Animals↗

Another approach for aortic valve replacement through left thoracotomy.

We report a 54-year-old man with a history of esophagectomy and retrosternal esophagogastric anastomosis for esophageal cancer through right thoracotomy in whom cardiac failure developed due to aortic regurgitation. He underwent aortic valve replacement through a left thoracotomy with division of two great arteries and their strong traction toward the surgeon by stay sutures. He has been well for 3 years postoperatively in New York Heart Association class I.

Anastomosis, Surgical↗

Ultrastructure of macrophages and dendritic cells in osteopetrosis (op) mutant mice lacking macrophage colony-stimulating factor (M-CSF/CSF-1) activity.

The ultrastructural features of macrophages and dendritic cells of mice homozygous for osteopetrosis (op/op) mutation were studied. The mutant mice are characterized by defective differentiation of osteoclasts, monocytes, and tissue macrophages due to the lack of functional macrophage colony stimulating factor (M-CSF/CSF-1) activity. In op/op mice, tissue macrophages were reduced in number and smaller than in normal littermates. Macrophages in op/op mice showed various degrees of phagocytosis but the development of intracytoplasmic organelles and microvillous projections was poor. After administration of CSF-1 daily for 2 weeks, macrophages in op/op mice developed lysosomes and microvillous projections. In the thymic medulla, T-cell zone of lymph nodes, splenic white pulp and epidermis of the op/op mice, the number of dendritic cells was similar to that in normal littermates and the dendritic cells developed a tubulovesicular system typical of interdigitating cells. Birbeck granules in epidermal Langerhans cells were detected in unmanipulated op/op mice, op/op mice injected with CSF-1, and normal littermates or control mice. However, in untreated op/op mice, dendritic cells projected shorter cytoplasmic processes than in normal littermates, normal control mice and CSF-1 injected op/op mice. These results indicate that the differentiation and maturation of tissue macrophages are mediated by CSF-1, but the dendritic cell differentiation is controlled by other factor(s) than CSF-1, most probably by GM-CSF.

Animals↗

The role of macrophage colony-stimulating factor in hepatic glucan-induced granuloma formation in the osteopetrosis mutant mouse defective in the production of macrophage colony-stimulating factor.

To elucidate the effects of macrophage colony-stimulating factor (M-CSF) on Kupffer cells and monocyte/macrophages in hepatic granuloma formation, we examined granulomas produced by glucan injection in the liver of osteopetrotic mice and littermates with or without M-CSF administration. In the osteopetrotic mice, monocytes were deficient in peripheral blood, and their number did not increase after glucan injection. Hepatic granulomas were formed in the osteopetrotic mice by glucan injection without a supply of blood monocytes. During this process, M-CSF-independent Kupffer cells proliferated, particularly before the granuloma formation, clustered in the hepatic sinusoid, and transformed into epithelioid cells and multinuclear giant cells. In the M-CSF-treated osteopetrotic mice, glucan injection induced an increase in the number of blood monocytes and formed hepatic granulomas at a nearly similar degree to that of littermate mice. Thus, it is concluded that neither monocytes nor M-CSF are necessary for granuloma formation. In contrast, Kupffer cells play a crucial role as granulomas develop in M-CSF-uninjected osteopetrotic mice.

Animals↗

Participation of the CYP2D subfamily in lidocaine 3-hydroxylation and formation of a reactive metabolite covalently bound to liver microsomal protein in rats.

Lidocaine metabolism was investigated in rat liver microsomes and in a reconstituted system containing P450BTL, a cytochrome (P450) isozyme belonging to the CYP2D subfamily (Suzuki et al., Drug Metab Dispos 20: 367-373, 1992). P450BTL biotransformed lidocaine into 3-hydroxylidocaine (3-OH-LID) but not monoethylglycinexylidide and 2-methylhydroxylidocaine, in the reconstituted system including NADPH-P450 reductase and dilauroylphosphatidylcholine. An antibody against P450BTL inhibited microsomal lidocaine 3-hydroxylase activity by 97%. Thus, P450BTL and/or its immunorelated P450 isozyme(s) belonging to the CYP2D subfamily appear to be involved in lidocaine 3-hydroxylation. Furthermore, the antibody also suppressed the amounts of a lidocaine metabolite(s) bound to microsomal protein. These results suggest that the CYP2D subfamily biotransformed lidocaine into 3-OH-LID via an epoxy intermediate, which binds to microsomal macromolecules.

Amino Acid Sequence↗

[Right ventricular myxoma--case report and review of the literature].

Primary tumors of the heart are rare, with the most common being myxoma, although myxoma of ventricular origin are uncommon. A careful review of the literature showed that 72 patients worldwide had cardiac myxomas located in the right ventricle. A 13-year-old asymptomatic girl with no previous history of cardiac disease was referred to a local hospital for evaluation of a heart murmur detected during a routine medical examination. Right ventricular myxoma was diagnosed and confirmed by echocardiogram, angiocardiography, CT, and MRI, MRI was firstly performed of right ventricular myxoma, and that showed right ventricular myxoma and the myocardium at the same intensity. Surgery was performed by first opening the right atrium. A lobulated mass was visualized through the tricuspid valve. Using a long needle, we confirmed that the wall was attached to the pedicle of the myxoma. Right ventriculotomy was subsequently performed in this region. The mass was passed through the tricuspid valve, and was reseated along with surrounding myocardium but with minimal excision of the right ventricular wall. The excised myxoma weighed 11 g, and had developed a short and small pedicle (5 mm x 5 mm) on the free wall and septum of the right ventricle. The patient recovered uneventfully and was discharged two weeks after the operation.

Adolescent↗

[Assessment of left ventricular contraction with LV Emax during cardiopulmonary bypass in patients with open heart surgery].

There are few reports on the assessment of left ventricular contraction during cardiopulmonary bypass (CPB) in open heart surgery. LV Emax is thought to be a load-independent index of left ventricular function. We used a left ventricular conductance catheter to measure LV Emax from "non-working beating heart" during CPB in 16 patients who underwent open heart surgery. During CPB, at 45 minutes after aortic declamping, changes of heart rate with atrial pacing (120/min) did not change LV Emax, but after intravenous dobutamine administration (DOB, 10 micrograms/kg/min) LV Emax increased by 26% (p < 0.01). DOB increased LV Emax in 14 of 16 patients during CPB. These 14 patients were weaned from CPB without difficulty. But in 2 other patients DOB didn't increase LV Emax during CPB. In order to be weaned from CPB, the two patients needed epinephrine and intraaortic balloon pumping. We concluded that change of LV Emax made by intravenous administration of dobutamine is one of useful indexes to assess left ventricular contractility during cardiopulmonary bypass.

Cardiopulmonary Bypass↗

Regio- and stereoselective propranolol metabolism by 15 forms of purified cytochromes P-450 from rat liver.

Regio- and stereoselectivity of cytochrome P-450-mediated propranolol metabolism (4-, 5- and 7-hydroxylations and N-desisopropylation) was studied using 15 purified cytochrome P-450 species. With each purified cytochrome P-450 species, the regioselectivity was distinct and different between the two optical isomers used as substrates. The stereoselectivity was different depending on the position of propranolol to be metabolized. The regio- and stereoselectivity was altered when substrate concentration was altered, suggesting that the kinetics of the reactions are different depending on the positions of propranolol to be metabolized. Furthermore, the selectivity and its manner of alterations with substrate concentrations were different among all cytochrome P-450 species used. Propranolol, with its multiple metabolic pathways and optical isomers, is an extremely interesting substrate for characterization of cytochrome P-450 species.

Amino Acid Sequence↗