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Biomedical subjects

Y Ishikawa

Publications and source records attributed to Y Ishikawa.

At least 127 records · Page 7Linked to original sources

Scintigraphic evaluation of pamidronate and corticosteroid therapy in a patient with progressive diaphyseal dysplasia (Camurati-Engelmann disease).

A 27-year-old woman with progressive diaphyseal dysplasia (Camurati-Engelmann disease) received pamidronate and corticosteroid therapy for bone pain. During therapy, disease activity was assessed serially using bone scintigraphy with Tc-99m HMDP. With pamidronate administration, the bone pain became worse and diaphyseal uptake of Tc-99m HMDP increased, whereas corticosteroid administration improved the bone pain and reduced the diaphyseal uptake. In this case, pamidronate and corticosteroid produced different effects. Bone scintigraphy allowed an objective assessment of the response to these treatments, accurately reflecting clinical symptoms.

Administration, Oral↗

Bovine nasal eosinophilic, granuloma with blood eosinophilia caused by Nocardia species.

OBJECTIVE: To describe a case of nocardial nasal granuloma in a Holstein heifer. CLINICAL FEATURES: The heifer showed laboured respiration and occasional coughing with granulomatous excrescences on the bilateral nasal mucosa, and a marked leucocytosis with eosinophilia. NECROPSY: Severe granulomatous inflammation with eosinophils, epithelioid cells, giant cells and Nocardia sp obstructed both nasal passages completely. CONCLUSION: This lesion resulted from chronic infection with Nocardia sp and is distinct from other forms of bovine nasal granuloma, also called atopic rhinitis or chronic granular rhinitis, which we propose should be classified as bovine allergic granular rhinitis. The most appropriate name for the present disease is bovine nasal eosinophilic granuloma.

Animals↗

Brain structures of a medaka mutant, el (eyeless), in which eye vesicles do not evaginate.

Eye development and brain structures of a mutant teleost fish were investigated. The el (eyeless) mutation in medaka (Oryzias latipes) is recessive and affects eye formation; in the most severe cases, it results in the absence of eyes. Developmental studies revealed that normal eyeballs are not formed in the el mutant embryos, but small optic cup-like structures differentiate in situ in the walls of the prosencephalon without evagination. The anophthalmic el homozygous fish hatched normally, although they did not respond behaviorally to visual stimuli. A small fraction of these fish grew to adulthood. In the adult anophthalmic el homozygous fish, the brain exhibited abnormalities in several subdivisions. A pair of small abnormal protrusions was observed on the surface of the ventral telencephalon and preoptic area. Immunocytochemistry using a rhodopsin monoclonal antibody showed that opsin-positive cells were present in the abnormal structures. Bodian staining showed that the optic nerves were present near the abnormal structures, although the number of optic nerve fibers was extremely small. The optic tectum was extremely small, and the thickness of the stratum opticum and stratum fibrosum et griseum superficiale was reduced. These behavioral and morphological observations suggest that the adult anophthalmic el homozygous fish are functionally blind, although small retina-like structures were partially differentiated and persisted in the adult fish brain. Moreover, the adult anophthalmic el homozygous fish were infertile, and the sizes of the hypophysis and the hypothalamus were reduced. Thus, the el mutation affects not only the brain structures that are related to the visual system but also those related to the reproductive system.

Animals↗

Explanted glomeruli: utility and limitations.

Ex vivo incubation of isolated glomeruli has been used for many years to investigate biochemical properties of glomeruli. However, little has been understood about whether and how isolation and explanation per se affect the structure and function of the glomerulus. We recently reported that ex vivo incubation of isolated normal glomeruli results in severe apoptosis of podocytes, activation of the family of mitogen-activated protein kinase and expression of several genes regulated by activator protein 1. In this article, we summarize our current findings and discuss the utility and limitations of explanted glomeruli.

Animals↗

Solution properties and photonuclease activity of cationic bis-porphyrins linked with a series of aliphatic diamines.

The development of efficient photo-induced DNA cleavage agents has been of particular interest for biomedical applications such as cancer photodynamic therapy (PDT). Toward this objective, we synthesized a series of cationic bis-porphyrins with various lengths of diamino alkyl linkage, N,N'-bis[4-[10,15,20-tris(1-methylpyridinium-4-yl)porphyrin-5-yl]benzoyl]oligomethylenediamine hexaiodide. They were expected to show more efficient photocleavage of DNA than unichromophore meso-tetrakis(4-N-methylpyridiniumyl)porphine (TMPyP), which is well known to cleave DNA effectively on illumination. The cationic bis-porphyrins were found to self-aggregate in aqueous solution, and the aggregation property was accounted for by the formation of an intermolecular dimer. Because conservative-type circular dichroism spectra of the bis-porphyrins were induced in the Soret region on binding to calf thymus DNA, we assigned their binding mode to outside self-stacking on the DNA surface. Their photonuclease activity using plasmid DNA decreased as the number of their linker hydrocarbons increased, and was well correlated with their tendency for dimerization. The inhibitory effect of azide anion, N3-, and the enhancement effect of D2O suggest that singlet oxygen was probably involved in the photocleavage of DNA.

Circular Dichroism↗

Efficient photocleavage of DNA by cationic porphyrin-acridine hybrids with the effective length of diamino alkyl linkage.

Positively charged porphyrins bearing an acridine with various lengths of diamino alkyl linkage, 5-[4-[(6-chloro-2-methoxy-9-acridyl)aminoalkylaminocarbonyl]phenyl]-10,15,20-tris(4-N-methylpyridiniumyl)porphine triiodide, alkyl=ethyl, butyl, hexyl, or octyl, were synthesized. They exhibited more enhanced photocleavage activity of pUC18 plasmid DNA than TMPyP, meso-tetrakis(4-N-methylpyridiniumyl)porphine, which is well known to bind to DNA tightly and to cleave DNA effectively; the hybrid linked with the hexamethylene chain showed particularly high activity. An equilibrium dialysis experiment demonstrated that the binding ability of the hybrids to calf thymus (CT) DNA correlated quantitatively with the photocleavage activity. The lack of the substantial red-shift of the Soret maxima of the hybrids through the titration with CTDNA denied the intercalative binding of the porphyrin part. In their circular dichroism (CD) spectral change on binding to CTDNA, two negative peaks appeared at 275 nm and at 285-290 nm in the UV range. The latter negative peak was observed for hybrids, but not for TMPyP, and thus we assigned it to induced CD (ICD) derived from intercalation of acridine chromophore. In the visible range, the hybrids showed only a positive peak around their Soret maxima, and this feature suggested the porphyrin moiety lay in the DNA groove. In addition, the length of the linker markedly influenced the ellipticity of their visible ICD, suggesting that the proximity of the porphyrin moiety to DNA was greatly affected by the linker.

Acridines↗

[Low dose CVD chemotherapy as a tumor dormancy therapy for extra-adrenal malignant pheochromocytoma: a case report].

A 38 year-old man presented with upper abdominal mass and hypertension pointed out at a medical examination. Blood pressure was 170/90 under medication of an alpha-blocker. Abdominal CT scan showed an 8 x 8 cm inter-aortocaval mass displacing pancreas head ventrally, and further a 4 x 4 cm mass at the aortic bifurcation, but there was no tumorous lesion in bilateral adrenal glands. Plasma nor-epinephrine level and urinary VMA excretion were excessive but plasma adrenaline level was within normal limits. MIBG scintigram showed hot spots in the 4th and 9th thoracic vertebrae. The destructive change of the 9th vertebra on magnetic resonance imaging strongly suggested metastasis of the tumor. Histologic and immunohistochemical findings of the biopsy specimen taken from the lower abdominal tumor in addition to the above clinical data led to the diagnosis of extra-adrenal malignant pheochromocytoma with spinal metastases. Since 2 cycles of full dose CYVADIC chemotherapy had no effects on lowering the high blood pressure and reducing the tumor size, low dose (60% of the full dose) CVD (cyclophosphamide, vincristine and dacarbazine) was given as a palliative chemotherapy on an out-patient clinic approximately every 4 weeks. After 4 cycles of the chemotherapy, his backache due to spinal metastasis markedly improved, hypertension as well as the plasma dopamine level was normalized and nor-epinephrine level was markedly decreased, though the tumor size was not reduced. Thereafter, no medication for hypertension was necessary. During 3 years and 6 months until now, 36 cycles of the chemotherapy has been repeated with no significant side effects. He has been at full-time work with quality of life being well preserved. Low dose CVD regimen appears to be an effective tumor dormancy therapy for advanced extra-adrenal pheochromocytoma.

Abdominal Neoplasms↗

[Carinal resection for bronchogenic carcinoma].

The purpose of this study was to evaluate the results of carinal resection for bronchogenic carcinoma in our institute. From 1981 to 1999, 24 carinal resection were performed for squamous cell carcinoma (n = 19), adenoid cystic carcinoma (n = 2), small cell carcinoma (n = 1), adenocarcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). Nineteen underwent sleeve pneumonectomy, 2 had carinal resection without lung resection, 2 had carinal resection with right middle and lower lobectomy, and 1 had wedge pneumonectomy. In the patients with sleeve or wedge pneumonectomy, there were 5 operative death and 3 patients had survived for more than 3 years. Two patients with low-grade malignant tumors underwent carinal resection without lung resection and survived more than 10 years. We believe that limited carinal resection for low-grade malignant tumors are safe and valuable procedure. Careful selection of patients with sleeve or wedge pneumonectomy is mandatory.

Adult↗

[A case of squamous cell carcinoma of the bladder that was successfully treated with multidisciplinary therapies].

A 45-year-old man with hematopyuria detected at another hospital visited our department for further examination. Endoscopic examination revealed a disintegration abscess between the bladder neck and prostatic urethra. Transurethral biopsy demonstrated squamous cell carcinoma of the bladder. He received 40 Gy of radiation combined with M-VAC (methotrexate, vinblastine, dovorubicin cisplatin) chemotherapy. Pathologically, a complete response was found when he underwent total cystourethrectomy. There has been no sign of recurrence for one and a half years postoperatively.

Antineoplastic Combined Chemotherapy Protocols↗

Comparison of cardiac sympathetic nervous function with left ventricular function and perfusion in cardiomyopathies by (123)I-MIBG SPECT and (99m)Tc-tetrofosmin electrocardiographically gated SPECT.

UNLABELLED: The objective of this study was to clarify the relationship between cardiac sympathetic nervous function (CSNF) and left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-eight cases (32 males, 6 females; mean age, 56 +/- 15 y), consisting of 5 healthy control subjects, 15 patients with DCM, and 18 patients with HCM, were studied with (123)I-metaiodobenzylguanidine (MIBG) and (99m)Tc-tetrofosmin SPECT. CSNF was evaluated from cardiac uptake and washout of MIBG, whereas LV perfusion and function were evaluated from tetrofosmin uptake and wall thickening on electrocardiographically gated SPECT. As quantitative parameters of global cardiac MIBG uptake and washout, the heart-to-mediastinum ratio (H/M) and percentage washout were calculated from early and delayed planar images. As quantitative regional parameters, the regional uptake and percentage washout of MIBG were calculated from SPECT images dividing the left ventricle into 12 segments. In the tetrofosmin study, the H/M and LV ejection fraction were calculated as the parameters of global LV perfusion and function. As quantitative regional parameters, the regional uptake and wall thickening were also calculated for the 12 myocardial segments using the quantitative gated SPECT software. Multiple linear regression analysis was performed to investigate the correlations between the parameters from the 2 studies. RESULTS: In DCM and HCM, multiple linear regression analysis of the regional parameters showed significant correlations between LV function and CSNF (P < 0.0001) and between LV perfusion and CSNF (P < 0.0001). According to the partial correlation coefficients, washout and early uptake of MIBG were the most significant factors for predicting LV function and LV perfusion, respectively. CONCLUSION: In cardiomyopathies, CSNF was closely related to LV function. The quantitative parameters of MIBG washout could reflect cardiac functional impairment. Early MIBG uptake might be determined by myocardial perfusion in cardiomyopathies.

3-Iodobenzylguanidine↗

Alpha-particle carcinogenesis in Thorotrast patients: epidemiology, dosimetry, pathology, and molecular analysis.

We studied the alpha-radiation risks in patients who received injections of Thorotrast, an X-ray contrast medium used in Europe, Japan, and the United States from 1930 to 1955. Thorotrast was composed of thorium dioxide (ThO2) and Th-232, a naturally occurring radionuclide. Because the physical half-life of ThO2 is 14 billion years and Thorotrast is hardly eliminated from the body, tissues in which it was deposited are irradiated by alpha-radiation for the entire lifetime of the subject. The dosimetry of Thorotrast patients is very complicated, but currently its reliability is quite high compared with other irradiated populations. The major causes of the death of Thorotrast patients are liver cancer, liver cirrhosis, leukemia, and other cancers. Three histologies of liver cancer are found: cholangiocarcinoma, hepatocellular carcinoma, and angiosarcoma. Although cholangiocarcinoma is the most frequent, angiosarcoma is characteristic of alpha-radiation. Among blood neoplasms with a higher incidence of increase than the general population, erythroleukemia and myelodysplastic syndrome were remarkable. Thorotrast patients exhaled a high concentration of radon (Rn-220), a progeny of Th-232, but no excesses of lung cancer in the patients of Japan, Germany, and Denmark were reported. Mutation analyses of p53 genes and loss of heterozygosity (LOH) studies at 17p locus were performed to characterize the genetic changes in Thorotrast-induced liver tumors. Interestingly, LOH, supposedly corresponding to large deletions was not frequent; most mutations were transitions, also seen in tumors of the general population, suggesting that genetic changes of Thorotrast-induced cancers are mainly delayed mutations, and not the result of the direct effects of radiation.

Adult↗

Comparison of the antigenicity of protoscoleces and microvesicles of Echinococcus multilocularis prepared from rats.

Rats are known to be relatively resistant to infection with Echinococcus multilocularis. However, when rats are inoculated with the parasite tissues, E. multilocularis proliferates slowly at first but after 6 months the cysts increase in size considerably and contain large numbers of protoscoleces. As rats survive for 18 months or longer, approximately 100 ml of packed protoscoleces can be produced from each rat. A comparison of the antigenicity of the protoscoleces and microvesicles by immunoblot methods showed that both Em18 and Em16 are shared components between both protoscoleces and microvesicles, although the latter have some additional antigenic components. In antigens prepared from protoscoleces, the banding patterns around Em18 were much simpler than those from microvesicles. Therefore, for serodiagnosis of E. multilocularis, antigens should be carefully prepared from protoscoleces rather than microvesicles from the rat.

Animals↗