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Biomedical subjects

K Ishiguro

Publications and source records attributed to K Ishiguro.

At least 55 records · Page 3Linked to original sources

Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice.

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.

Animals↗

Accumulation of NACP/alpha-synuclein in lewy body disease and multiple system atrophy.

OBJECTIVES: NACP/alpha-synuclein is an aetiological gene product in familial Parkinson's disease. To clarify the pathological role of NACP/alpha-synuclein in sporadic Parkinson's disease and other related disorders including diffuse Lewy body disease (DLBD) and multiple system atrophy (MSA), paraffin sections were examined immunocytochemically using anti-NACP/alpha-synuclein antibodies. METHODS: A total of 58 necropsied brains, from seven patients with Parkinson's disease, five with DLBD, six with MSA, 12 with Alzheimer's disease, one with Down's syndrome, one with amyotrophic lateral sclerosis (ALS), three with ALS and dementia, one with Huntington's disease, two with progressive supranuclear palsy (PSP), one with Pick's disease, one with myotonic dystrophy, and three with late cerebellar cortical atrophy (LCCA), and 15 elderly normal controls were examined. RESULTS: In addition to immunoreactive Lewy bodies, widespread accumulation of NACP/alpha-synuclein was found in neurons and astrocytes from the brainstem and basal ganglia to the cerebral cortices in Parkinson's disease/DLBD. NACP/alpha-synuclein accumulates in oligodendrocytes from the spinal cord, the brain stem to the cerebellar white matter, and inferior olivary neurons in MSA. These widespread accumulations were not seen in other types of dementia or spinocerebellar ataxia. CONCLUSION: Completely different types of NACP/alpha-synuclein accumulation in Parkinson's disease/DLBD and MSA suggest that accumulation is a major step in the pathological cascade of both diseases and provides novel strategies for the development of therapies.

Aged↗

Complete antithrombin deficiency in mice results in embryonic lethality.

Antithrombin is a plasma protease inhibitor that inhibits thrombin and contributes to the maintenance of blood fluidity. Using targeted gene disruption, we investigated the role of antithrombin in embryogenesis. Mating mice heterozygous for antithrombin gene (ATIII) disruption, ATIII(+/-), yielded the expected Mendelian distribution of genotypes until 14.5 gestational days (gd). However, approximately 70% of the ATIII(-/-) embryos at 15.5 gd and 100% at 16.5 gd had died and showed extensive subcutaneous hemorrhage. Histological examination of those embryos revealed extensive fibrin(ogen) deposition in the myocardium and liver, but not in the brain or lung. Furthermore, no apparent fibrin(ogen) deposition was detected in the extensive hemorrhagic region, suggesting that fibrinogen might be decreased due to consumptive coagulopathy and/or liver dysfunction. These findings suggest that antithrombin is essential for embryonic survival and that it plays an important role in regulation of blood coagulation in the myocardium and liver.

Animals↗

[Video-assisted thoracic surgery (VATS) for metastatic lung tumor: comparison with thoracotomy].

Effectiveness and present problems of video-assisted thoracic surgery (VATS) for metastatic lung tumor were investigated by comparing 14 cases (16 operations) of VATS with 16 cases (19 operations) of conventional thoracotomy during the same period. VATS was favorably selected in the solitary metastasis. The cases who had small tumor diameter less than 3 cm and shorter distance from viseral pluera to the tumor surface than tumor diameter were advantageous for only thoracoscopic procedure to do the safe and sure resection. Regarding to the tumor number, we detected another tumor intraoperatively in 2 of 16 cases (12.5%) of VATS and 6 of 19 cases (31.6%) of thoracotomy. Multiple metastases had the tendency to have the differences of the tumor number between preoperation and intraoperation. Prognosis is very good until now, but the recurrence rate was high (64.5%) and one case had the recurrence at the surgical margin. VATS for metastatic tumor is very effective, but it is important not to hesitate to do the mini-thoracotomy and convert to conventional thoracotomy for safe and sure resection.

Adult↗

[Malignant cardiac lymphoma].

A 65-year-old male was admitted to the hospital in shock. The transesophageal echocardiography showed cardiac tumor in the right atrium. The tumor was resected under cardiopulmonary bypass. It was diagnosed as malignant lymphoma of B-cell type by histological examination. After operation, his general condition became satisfactory. Then he received chemotherapy. Twenty days after operation, however, a mass appeared in the right side of chin. It was diagnosed as malignant lymphoma of the same cell type as in the heart. We searched his body with CT and Ga-scanning. No other lesions were found. After the chemotherapy (CHOP, 6 cycles), the mass disappeared. No recurrence was been observed for six months.

Aged↗

[A new method of reconstruction for chest wall resection].

Sixteen patients who involved in chest wall disease underwent major chest wall resection between April 1995 and January 1999. The underlying diseases were 6 recurrence of breast cancers, 4 direct invasion by primary lung cancer, 2 metastatic chest wall tumor, one direct invasion by metastatic lung tumor, one direct invasion by metastatic mediastinal tumor, one radio-induced-necrosis of the chest wall, and one chest wall infection. In 9 patients, the thoracic cage reconstruction was performed using double sheets of absorbable mesh (Dexon mesh), cross string sutures and autologous ribs grafts. None of the patients had major respiratory failure and chest wall unstability. No late complications including infections, pains, recurrence and others related to reconstruction materials have been observed.

Aged↗

[Thoracoscopic surgery for pulmonary nodules in patients with previous malignant tumor].

We evaluated the clinico-pathological characteristics of thirty-four cases with previous malignant tumor who was operated under thoracoscopy for pulmonary nodules. In twenty-three cases (67.6%), including 20 cases suspected metastatic pulmonary tumor before operation, thoracoscopic surgery was performed without doing the preoperative examinations for the definite diagnosis. The mean diameter of resected tumors was 13.5 mm and the definite diagnosis was determined in all cases by the intraoperative pathological diagnosis. There were 26(76.5%) cases of malignancy, including 20 cases(58.8%) of metastatic pulmonary tumor and 6 cases (17.7%) of primary lung cancer. Accuracy rate of predictive diagnosis before operation was 67.6%. From the analysis of difference between pre- and post-operative diagnoses, inflammatory nodules or tuberculoma in the solitary nodule and intrapulmonary lymph nodes or silicotic nodules in the multiple nodules should have been considered with more carefully attention. Univariate and multivariate analysis showed that patients with metastatic tumor previously was only a predictive factor for metastatic tumor. Age, gender, CT findings, the number of nodules, disease free interval and tumor markers were unreliable factors in this study. In conclusion, there were a lot of cases with previous malignant tumor in which thoracoscopic surgery could become a first choice of modalities for the diagnosis of pulmonary nodules. Early thoracoscopic procedure will be recommended for such patients to perform the immediate treatment.

Adolescent↗

Thoracoscopic debridement for acute pediatric empyema: efficacy of ultrasonic surgical device.

Few studies have examined thoracoscopic treatment for pediatric empyema. We encountered three children with thoracic empyema successfully treated by thoracoscopic debridement. Patients were a 3-year-old girl, a 17 month-old boy and a 13-year-old girl who developed thoracic empyema during therapy for pneumonia. We performed dissection and debridement under thoracoscopy and resolved fibrinopurulent collections using an ultrasonic surgical device in two cases to search the dissection plane while minimizing injury to the lung parenchyma. Ultrasonic surgical device (USUTM) is very useful for performing effective debridement and irrigation with minimal pleural damage. Thoracoscopic debridement performed early in the course of therapy is recommended even for acute pediatric empyema and could prevent the unnecessary open surgical intervention or decortication.

Acute Disease↗

Starvation induces tau hyperphosphorylation in mouse brain: implications for Alzheimer's disease.

Hyperphosphorylated tau is the major component of paired helical filaments in neurofibrillary tangles found in Alzheimer's disease brains, and tau hyperphosphorylation is thought to be a critical event in the pathogenesis of this disease. The objective of this study was to reproduce tau hyperphosphorylation in an animal model by inducing hypoglycemia. Food deprivation of mice for 1 to 3 days progressively enhanced tau hyperphosphorylation in the hippocampus, to a lesser extent in the cerebral cortex, but the effect was least in the cerebellum, in correspondence with the regional selectivity of tauopathy in Alzheimer's disease. This hyperphosphorylation was reversible by refeeding for 1 day. We discuss possible mechanisms of this phenomenon, and propose the starved mouse as a simple model to study in vivo tau phosphorylation and dephosphorylation which are altered in Alzheimer's disease.

Alzheimer Disease↗

Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease.

Microtubule-associated protein tau in cerebrospinal fluid (CSF) has been proposed as a diagnostic marker for Alzheimer's disease (AD), but there is overlap between AD patients and non-AD controls. To improve the diagnostic accuracy, we measured phosphorylated tau in CSF, because phosphorylated tau accumulates as pathological paired helical filaments in neurons of the AD brain. Immunoblot showed that CSF contained a 32 kDa N-terminal fragment of tau that was partially phosphorylated on Ser199, Thr231 and Ser235. A sandwich enzyme immunoassay revealed that phosphorylated CSF-tau levels were significantly higher in AD patients than those in non-AD controls. Discrimination between the two groups was clearer in phosphorylated CSF-tau than in total CSF-tau. The data indicate that elevated phosphorylated CSF-tau level is a more specific diagnostic marker for AD.

Alzheimer Disease↗

Carboxyl-terminal fragments of presenilin-1 are closely related to cytoskeletal abnormalities in Alzheimer's brains.

To clarify the role of presenilin-1 (PS-1) in the pathology of Alzheimer's disease (AD), we tested four antisera to PS-1. The specific antisera to the N-terminus (HSN-2) and C-terminus (HS-C) of PS-1 detected a 44/40kD holoprotein, a 25kD N-terminal fragment (NTF) and a 16kD C-terminal fragment (CTF) of PS-1 in COS-7 cells. The 25kD NTF and 16kD CTF were observed in human brains, and their amounts were not significantly different between the control and AD brains. The antibody HS-C labeled extensive neurofibrillary tangles, dystrophic neurites and curly fibers in the AD brains. In the paired helical filament (PHF) fraction containing A68 protein from AD brains, a smear pattern of CTFs was revealed. Antisera (HS-L292 and HS-L300) to cleavage sites of PS-1 also revealed immunoreactive neurofibrillary tangles in the AD brain sections and the smear pattern of CTFs of A68 protein fraction. The CTFs of PS-1 accumulate with PHF tau, suggesting a close relationship between PS-1 and cytoskeletal abnormalities in AD brains.

Aged↗

Tyrosinase inhibitory p-coumaric acid from ginseng leaves.

By bioassay-guided fractionation using mushroom tyrosinase, p-coumaric acid was characterized as the principal tyrosinase inhibitor from the fresh leaves of Panax ginseng (Araliaceae). It inhibited the oxidation of L-tyrosine more strongly than that of L-3, 4-dihydroxyphenylalanine (L-DOPA) by this enzyme. On the basis of this finding, various related phenylpropanoid analogues were also tested in order to gain new insights into their structural criteria.

Agaricales↗

Screening method for PAF antagonist substances: on the phenolic compounds from Impatients balsamina L.

A blood pressure monitoring system was developed for studying antagonist effects against platelet activating factor (PAF), a chemical mediator of anaphylactic hypotension. Using this system, we were able to determine the inhibitory effects of a 35% ethanol extract (IB) from the petals of Impatiens balsamina L. against PAF-induced hypotension and the active principal compounds from IB. One mechanism of the antianaphylactic effects of IB was characterized as PAF-antagonist effects.

Anaphylaxis↗

Syndecan-4 expression is associated with follicular atresia in mouse ovary.

Ovarian granulosa cells synthesize heparan sulfate proteoglycans (HSPGs), that have anticoagulant properties. Moreover, HSPGs greatly increase in the granulosa cells during follicular atresia. However, the species of ovarian HSPGs have not yet been identified. Syndecan-4 (ryudocan, amphiglycan) is a membrane-spanning HSPG and a member of the syndecan family. Herein, we demonstrate that syndecan-4 is expressed in the granulosa cells of type 4-5b follicles and, most intensely, in those of the atretic follicles in the mouse ovary, as revealed by in situ hybridization. There is no relationship between syndecan-4 expression and age or sexual cycle stage. Compared with syndecan-4 expression, syndecan-1 and -3 are expressed more abundantly in postovulatory follicles and the corpora lutea, but less in the type 4-5b follicles and much less in the atretic follicles. Immunohistochemistry also demonstrates syndecan-4 expression in atretic follicles with apoptosis. The present study has revealed the distinct modes of expression of the syndecan family members, and the association of syndecan-4 expression and apoptosis in ovarian atretic follicles.

Animals↗

Immunocytochemical features of lens after cataract tissue--signalling molecules (growth factors, cytokines, other signalling molecules), cytoskeleton proteins, cellular and extracellular matrix proteins.

UNLABELLED: We examined the immunocytochemical features of after cataract tissue and cataractous lens epithelium prior to cataract surgery and at the time of surgery. METHODS: This study included 23 cases. Antibodies against the following antigens were used: epidermal growth factor (EGF), EGF receptor (EGF-R), fibroblast growth factor (FGF), FGF receptor (FGF-R), transforming growth factor (TGF)-beta, TGF-beta receptor II (TGF-beta -RII), insulin-like growth factor (IGF)II, platelet derived growth factor (PDGF)-AB, interleukin (IL)-6, IL-1 receptor II, tumor necrosis factor (TNF)-alpha, tissue plasminogen activator (TPA), prostaglandin (PG) E2, plasminogen activator inhibitor (PAI)-1, alpha smooth muscle actin (alpha-SMA), keratin, vimentin, myosin, fibronectin, laminin, types I, II, III, IV, V and VI collagen (Col), and lens epithelial cells (LECs). RESULTS: The following substances were present in posterior and anterior capsular fibrosis of after cataract: EGF, EGF-R, FGF, FGF-R, TGF-beta, TGF-beta-RII, IGF-II, PDGF-AB, IL-6, IL-1RII, TNF-alpha, PGE2, PAI-1, alpha-SMA, keratin, fibronectin, laminin, Type I col, Type II to VI col and LECs. Elschnig's pearls of after cataract expressed FGF-R, TNF-alpha, laminin and LECs. Soemmering's ring of after cataract tissue expressed EGF, FGF, FGF-R, IL-1RII, TPA, PAl-1, keratin and LECs. The following substances were present in cataractous lens epithelium prior to cataract surgery: EGF, EGF-R, FGF, FGF-R, TGF-beta-RII, IL-1-RII, TNF-alpha, PAI-1, keratin, laminin and LECs. The following substances were present in the lens epithelium of anterior capsules collected at the time of cataract surgery: EGF, EGF-R, FGF, FGF-R, TGF-beta, TGF-beta-RII, IGF-II, IL-6, IL-1-RII, TNF-alpha, PGE2, keratin, fibronectin, laminin, Type IV Col and LECs. CONCLUSIONS: These results prove that many kinds of signalling molecules and proteins exist in the process of after cataract formation.

Aged↗

Thoracoscopic surgery for intralobar pulmonary sequestration.

A 47-year-old male with intralobar pulmonary sequestration successfully treated by thoracoscopic surgery was reported. Preoperative selective angiography revealed two aberrant arteries originating from the left infraphrenic artery. Under thoracoscopy, adhesive tissues around the sequestered lung were dissected, aberrant arteries were divided and the sequestered lung was resected. We considered that preoperative detailed analysis of the aberrant artery was very important to safely perform thoracoscopic procedures for pulmonary sequestration.

Angiography, Digital Subtraction↗

Coinduction of embryonic and adult-type globin mRNAs by sodium butyrate and trichostatin A in two murine interleukin-3-dependent bone marrow-derived cell lines.

Using an RNase protection assay, globin mRNA species expressed in clones derived from Ba/F3 and B6SUtA cells transfected with the erythropoietin receptor (EpoR) and selected with erythropoietin (Epo) were compared with globin mRNA species induced in corresponding parental cells by sodium butyrate (SB) and trichostatin A (TSA). betaMajor/betaminor- and -1/-2-globin mRNAs were the major species, with trace amounts of epsilon-globin mRNA, formed in Epo-stimulated EpoR+ Ba/F3 clones, whereas SB and TSA allowed expression of all species of globin mRNAs, ie, epsilon, betah1, betamajor/betaminor, zeta, and -1/-2, in parental Ba/F3 cells. In contrast, epsilon- and -1/-2-globin mRNAs were the major species present in Epo-stimulated EpoR+ B6SUtA clones, whereas SB and TSA activated epsilon-, betah1-, betaS/betaT-, and -1/-2-globin genes in parental B6SUtA cells; zeta-globin mRNA was not detected in SB- and TSA-treated B6SUtA cells. Because TSA is a specific inhibitor of histone deacetylase, the mimicry of action exhibited by SB and TSA suggests that the effects of SB are mediated through its ability to inhibit histone deacetylase and that histone deacetylase is an integral part of the repression of globin genes in these interleukin-3-dependent cells. Efficient coinduction of embryonic and adult types of globin mRNA in bone marrow cell lines derived from adult mice indicates that adult hematopoietic precursors possess an embryonic nature. These cell lines are useful models to study the mechanism(s) of developmental globin gene switching.

Animals↗