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Biomedical subjects

A Kaneko

Publications and source records attributed to A Kaneko.

At least 109 records · Page 6Linked to original sources

Modulation by proinflammatory cytokines of Fas/Fas ligand-mediated apoptotic cell death of synovial cells in patients with rheumatoid arthritis (RA).

Synovial cell hyperplasia is a characteristic of patients with RA. Excessive proliferation of RA synovial cells is, in part, responsible for the synovial cell hyperplasia. In addition, synovial cell death that would reduce synovial cell number may be defective, leading to the hyperplasia. Thus, the defective control of cell death as well as cell proliferation may be of central importance in the pathogenesis of RA. In this study we analysed effects of proinflammatory cytokines on Fas/Fas ligand (FasL)-induced synovial cell apoptosis, and evaluated apoptosis-associated protein expression in the synovial cells in patients with RA. RA synovial cells expressed Fas antigen and lymphocytes infiltrating into RA synovium expressed FasL. Apoptotic synovial cells were detected within the sublining layer of RA synovium. Anti-Fas MoAb induced apoptosis of RA synovial cells in vitro, and proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-1beta, but not IL-6 or IL-8, inhibited the anti-Fas-induced apoptosis accompanying up-regulation of Bcl-2 protein expression and reduced expression of CPP32 and ICH-1L. Immunohistochemical study revealed that CPP32 and ICH-1L were expressed weakly in the RA synovial lining cells compared with osteoarthritis (OA) synovial lining cells. Thus, we found that although RA synovial cells could die via apoptosis through Fas/FasL pathway, apoptosis of synovial cells was inhibited by proinflammatory cytokines present within the synovium. Inhibition of apoptosis by the proinflammatory cytokines may contribute outgrowth of synovial cells that leads to pannus formation and the destruction of joints in patients with RA.

Antibodies, Monoclonal↗

Two types of calcium currents of the mouse bipolar cells recorded in the retinal slice preparation.

In the vertebrate retina, the bipolar cell makes reciprocal synapses with amacrine cells at the axon terminal. It has been postulated that amacrine cells may control the transmitter release from bipolar cells by modulating their calcium currents (ICa). To clarify this possibility calcium currents were studied in bipolar cells of the mouse retina using a slice preparation. ICa was identified by voltage clamp protocols, ionic substitution and pharmacological tools. Depolarization to -30 mV from a holding voltage of -80 mV induced an inward current consisting of an initial transient and a long-lasting sustained component. The transient component was inactivated by holding the membrane at more positive voltages. Addition of 100 microM nifedipine suppressed the sustained component, leaving the transient component almost intact. The sustained component was enhanced when external solution contained 0.1 microM Bay K 8644 or when the external Ca2+ was substituted by equimolar Ba2+. Omega-conotoxin (10 microM omega-ctxn GVIA) did not alter either component. We concluded that the transient component is a low-voltage activated T-type ICa, while the sustained component is a high-voltage activated L-type ICa. T-type ICa was recorded in all cells tested, while L-type ICa was found only in cells that retained axon terminals ramifying in the inner plexiform layer. Thus, it is highly likely that L-type ICa is generated at the axon terminal and contributes to the transmitter release from the bipolar cell. The present results confirm that in addition to the T-type ICa that had been previously described, bipolar cells of the mammalian retina also contain L-type ICa similar to the one that has been reported in bipolar cells of the goldfish. The use of retinal slice preparation allowed us to record this current that was not seen previously in the dissociated mouse bipolar cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Difficult tracheal intubation in patients with retinoblastoma caused by 13q deficiency.

Anesthetic management of retinoblastoma patients is unremarkable in most cases. Patients are most often babies and laryngoscopic procedures for intubation are usually easy. However, we recently experienced two cases with retinoblastoma with whom tracheal intubation was accomplished with difficulty. We report the two cases with a review of all 5-year records of retinoblastoma (rbl) in our institution. The cases we experienced recently were all patients with rbl with deletion of the long arm of thirteenth chromosome (13q-). In the 5-year review, the incidence of the difficult intubation was significantly higher (P < 0.05) in rbl with 13q- (4/11) than in rbl without 13q- (0/147). In our experience macroglossia was noted for the difficulty in the intubation. We assume that some patients with rbl will be cases of difficult intubation even to cannot ventilate-cannot intubate level when the results of their chromosomal analysis show a deletion on the thirteenth chromosome.

Anesthesia↗

Second primary rhabdomyosarcomas in patients with bilateral retinoblastoma: a clinicopathologic and immunohistochemical study.

We reviewed six cases of rhabdomyosarcoma as a rare second primary malignancy in children with bilateral retinoblastoma after irradiation treatment. The patients comprised four females and two males (age range 1 year 4 months-7 years 11 months). Second tumors arose in the temporal muscle inside or close to the previously irradiated fields. All the children were alive and well 24-72 months after diagnosis. Microscopic examination showed proliferation of closely packed, small round cells with scanty cytoplasm, coarse nuclear chromatin, and increased mitotic activity without a myxoid background nor obvious alveolar architecture. The most characteristic feature was the presence of rosette-like structures in four tumors. Immunoreactivity for many skeletal muscle markers was evident, including desmin (six of six), muscle-specific actin (HHF35) (six of six), sarcomeric actin (six of six), myogenin (six of six), vimentin (six of six), and myoglobin (three of six). On reverse transcriptase-polymerase chain reaction examination, three second tumors lacked specific chimeric transcripts for alveolar rhabdomyosarcoma and Ewing's sarcoma. Unexpectedly, variable reactivity for neurofilament (150 kd) was identified in six of six second tumors as well as 15 of 20 sporadic primary rhabdomyosarcomas (75%) examined as controls, the result being confirmed by Western blot analysis. In addition, staining for retinoblastoma-susceptibility gene protein was negative in all second tumors, in contrast to positivity in 14 of 17 sporadic primary tumors (82%). This finding suggests that retinoblastoma-susceptibility gene abnormalities could be associated with the development of second primary rhabdomyosarcoma. We consider that knowledge of the occurrence of rhabdomyosarcoma and appropriate immunohistochemical study are helpful for avoiding a misdiagnosis of recurrent retinoblastoma or Ewing's sarcoma when encountering patients with a history of bilateral retinoblastoma who developed second small round cell neoplasms.

Antigens, Neoplasm↗

Color-coded Doppler imaging of subclavian steal syndrome.

We examined the usefulness of color-coded Doppler echography for evaluating hemodynamics in patients with subclavian steal syndrome. Eighteen patients with subclavian steal syndrome, aged 54 to 77 years, were investigated. The diagnosis was confirmed by conventional angiography and pulsed-wave Doppler sonography. Using color-coded Doppler echography, the common, internal and external carotid and vertebral arteries and the subclavian artery on the affected side were visualized. In all patients, color-coded images of the antegrade common carotid arterial flow and the retrograde vertebral arterial flow on the affected side were obtained. Rapid flow through stenotic lesions and reflux from vertebral to subclavian arteries at the vertebral arterial ostia were observed. Color-coded Doppler echography is superior to duplex echography without the color-coded mode, because the flow through the affected vertebral and subclavian arteries can be easily traced in detail and the images are persuasive. This method is beneficial for diagnosing subclavian steal syndrome.

Aged↗

[Polymyalgia rheumatica and myelitis associated with anti-cardiolipin antibody].

A 78-year-old woman was admitted to our hospital on September 14, 1992, because of systemic myalgia and stiffness, joint pain, and gait disturbance. She had begun to feel headache and pain in the neck and shoulder in the middle of August, 1992. The pain became systemic, and was accompanied by a low-grade fever, which was unresponsive to NSAIDs. On admission, she had no joint swelling or deformities in the extremities. Neurological examination revealed weakness in the right leg, hypoalgesia below the left C4 level, hyperreflexia in the right extremities, and right Babinski's sign. The erythrocyte sedimentation rate was very high (100 mm/h). Levels of other acute phase reactants were also high. Tests for antinuclear antibody and anti-cardiolipin antibody were positive, but a test for rheumatoid factor was negative. Creatine kinase activity was within normal limits. A T1-weighted magnetic resonance image of the cervical spine at 0.5 T showed an intramedullary low signal. A T2-weighted image showed a borderless spindle-like high signal. Four nodules enhanced by Gd DTPA were seen at C1-C4. The age at onset, myalgia, stiffness, and erythrocyte sedimentation rate were considered to be consistent with a diagnosis of polymyalgia rheumatica. Glucocorticoid treatment was therefore started, and a dramatic clinical improvement was evident within a few days. The patient was discharged from hospital on November 30, 1992. To our knowledge, myelopathy complicated by polymyalgia rheumatica has never been reported previously. Recently, some patients with polymyalgia rheumatica have been reported to have anti-cardiolipin antibody in serum. In the present case anti-cardiolipin antibody may have played a role in the formation of microemboli or in angitis of the cervical spine.

Aged↗

[TNM classification of ophthalmic malignant tumors].

The present TNM classification of ophthalmic malignant tumors (lid cancer, malignant melanoma of the lid, conjunctival cancer, conjunctival malignant melanoma, uveal malignant melanoma, retinoblastoma, orbital sarcoma and lacrimal gland cancer) has been explained according to the UICC in a book edited by M. H. Harmer and J. A. Oosterhuis. Five studies concerning the difference in clinical results with and without a treatment were shown to confirm the meaning and importance of TNM classification of ophthalmic malignancies.

Conjunctival Neoplasms↗

[Malaria on the global agenda: control and chemotherapy of malaria in Vanuatu].

Even now 50% of the world population are still living in malaria endemic areas and every year 200 million new cases with 2 million deaths are reported. Most of the malaria deaths are children under 5 years old. Although malaria endemicity currently exists mainly in tropics, before the human started its efforts to eradicate malaria in large scale in 1950s, malaria was more widely distributed in the world. At this time Japan and malaria together with North America and European countries. However some areas were precluded from malaria endemicity: i.e., high mountains and deserts. Also Polynesian islands in the Pacific have never been malarious, even though Melanesian Papua New Guinea, Solomon, and Vanuatu are highly malarious even now. Human disease malaria is caused by Plasmodium parasites and transmitted by Anopheles mosquitoes. Human is classified into the malaria donor and recipient. The environment is supporting this system: for example, temperature and rainfall are important factors together with vegetation, or housing, health infrastructure, war situation, and poverty status. In 1950s, the WHO malaria eradication program focused its efforts on vector control, using DDT-residual spraying. But the program completely failed with mainly operational reasons and we already learned it is almost impossible to control malaria only killing mosquitoes. In 1992 the new Global Malaria Control Strategy adopted by Malaria Summit at Amsterdam says the primary objective is early diagnosis and treatment to prevent malaria death. In this context malaria chemotherapy is a key issue. Also we understand more and more the environmental management is very important. Malaria vaccine may be a conceptually important tool, but may be available soon.

Animals↗

[Prevalence of pressure ulcers of patient in home visiting nursing service].

PURPOSE: To determine prevalence and risk factors for pressure ulcers of subjects in visiting nursing service stations. METHOD: Descriptive cross-sectional study. Data were collected by a mail survey questionnaire from 934 visiting nursing service stations that were listed in "Visiting nursing service stations list" in September 1995. RESULTS: Responses from 620 visiting nursing service stations were obtained (collection rate 66.4%). The sample consisted of 23,500 subjects, with a pressure ulcer prevalence rate of 14.6% (n = 3,441). Furthermore, the prevalence was 15.1% (n = 3,177) in the elderly of 65 years and older (n = 21,020). The observed prevalence among visiting nursing service stations ranges from 4.8% to 24.1%. In subjects with pressure ulcers, there were high rates of cerebral vascular diseases, dementia, Alzheimer's disease, urinary organ system diseases, and senility. On the other hand, subjects without pressure ulcers, had high rates of ischemic heart diseases, chronic respiratory organ diseases, and mental disease. The total number of pressure ulcers that were observed in 3,441 subjects was 5,158 and the number of the pressure ulcers per person was 1.64. The level of depth of I, II were observed at around 40%. CONCLUSION: The number of elderly people who necessitate medical treatment or nursing care in homes will be increasing in the future. A survey is needed to develop a program that will be efficient in early detection and care of pressure ulcers.

Aged↗

Anti-streptococcal activity of homologous polymorphonuclear neutrophils from patients with surgically treated oral infections.

The phagocytic bactericidal activity of homologous polymorphonuclear neutrophils (PMN), obtained from patients with severe, moderate and mild oral infections with Streptococci, was investigated. The drop in viable bacterial cell counts in PMNs from 3 patients with a severe infection, after 4 hours of incubation, was much greater than in PMNs from moderate or mild infections. We conclude that the phagocytic bactericidal activity of PMNs is stronger in patients suffering from severe oral infections with Streptococci.

Adult↗

Leptin stimulates the proliferation of murine myelocytic and primitive hematopoietic progenitor cells.

Leptin, the product of obese gene, was originally identified as a factor regulating body-weight homeostasis and energy balance. The present study has shown that leptin acts on murine hematopoiesis in vitro. In the culture of bone marrow cells (BMC) of normal mice, leptin induced only granulocyte-macrophage (GM) colony formation in a dose-dependent manner, and no other types of colonies were detected even in the presence of erythropoietin (Epo). Leptin also induced GM colony formation from BMC of db/db mutant mice whose leptin receptors were incomplete, but the responsiveness was significantly reduced. The effect of leptin on GM colony formation from BMC of normal mice was also observed in serum-free culture, and comparable with that of GM-colony-stimulating factor (CSF ). Although leptin alone supported few colonies from BMC of 5-fluorouracil (5-FU)-treated mice in serum-free culture, remarkable synergism between leptin and stem cell factor (SCF ) was obtained in the colony formation. The addition of leptin to SCF enhanced the SCF-dependent GM colony formation and induced the generation of a number of multilineage colonies in the presence of Epo. When lineage (Lin)-Sca-1(+) cells sorted from BMC of 5-FU-treated mice were incubated in serum-free culture, leptin synergized with SCF in the formation of blast cell colonies, which efficiently produced secondary colonies including a large proportion of multilineage colonies in the replating experiment. In serum-free cultures of clone-sorted Lin-c-Kit+Sca-1(+) and Lin-c-Kit+Sca-1(-) cells, although synergism of leptin and SCF was observed in the colony formation from both cells, leptin alone induced the colony formation from Lin-c-Kit+Sca-1(-), but not Lin-c-Kit+Sca-1(+) cells. These results have shown that leptin stimulates the proliferation of murine myelocytic progenitor cells and synergizes with SCF in the proliferation of primitive hematopoietic progenitors in vitro.

Animals↗

Ligand-dependent heterodimerization of thyroid hormone receptor and retinoid X receptor.

The thyroid hormone receptors (TR) bind to cis-acting DNA elements as heterodimers with the retinoid X receptors (RXR). These heterodimers display distinct specificities in mediating the hormonal response to target gene transcription. We characterized the interaction between TRalpha1 and RXRalpha via their ligand binding domains (LBDs) and the effect of ligands on the interaction using a yeast two-hybrid system. The DNA binding domain (BD) of yeast Gal4 fusion to the LBD of TRalpha1 had no transcriptional activity on its own, but when it was coexpressed with the activation domain (AD) of yeast Gal4 fusion to LBD of RXRalpha conferred activation to a reporter gene harboring a Gal4 binding site, indicating that LBDs of TRalpha1 and RXRalpha interact with each other in solution. Furthermore, T3 and 9-cis-RA increased the reporter activity, and an additive effect was observed when both ligands were added, indicating that the TRalpha1.RXRalpha heterodimerization is augmented by their respective ligands in vivo. Using an in vitro pull-down experiment, we confirmed the ligand-dependent interaction observed in the yeast system. Matrix-bound glutathione S-transferase-RXRalpha specifically coprecipitated the 35S-labeled TRalpha1 above the control, and associated 35S-labeled TRalpha1 was increased by the addition of T3 and 9-cis-RA. These results imply a complex, sensitive cross-talk in vivo among nuclear receptors and their respective ligands through distinct hormonal signaling pathways.

Alitretinoin↗

Elevation of serum creatine kinase during treatment with antithyroid drugs in patients with hyperthyroidism due to Graves disease. A novel side effect of antithyroid drugs.

We describe 4 patients with Graves disease who had abnormal increases of serum creatine kinase (CK) concentrations during treatment with antithyroid medications. Three of the patients experienced myalgia and muscle cramps. All of the patients manifested an increase in serum CK levels 1 to 3 months after the administration of antithyroid drugs. Thyrotropin concentrations and cardiac systolic time indexes during the elevation of serum CK concentrations were not consistent with hypothyroidism. The mechanisms are not obvious, but it is likely that the rapid decrease of thyroid hormones in tissues may temporarily cause hypothyroid states, resulting in alterations in CK concentrations. It is suggested that hasty correction of thyrotoxicosis should be avoided in susceptible patients, unless the thyrotoxic conditions are critical.

Adult↗

Inhibition of peroxisome proliferator signaling pathways by thyroid hormone receptor. Competitive binding to the response element.

Peroxisome proliferators (e.g. clofibric acid) and thyroid hormone play an important role in the metabolism of lipids. These effectors display their action through their own nuclear receptors, peroxisome proliferator-activated receptor (PPAR) and thyroid hormone receptor (TR). PPAR and TR are ligand-dependent, DNA binding, trans-acting transcriptional factors belonging to the erbA-related nuclear receptor superfamily. The present study focused on the convergence of the effectors on the peroxisome proliferator response element (PPRE). Transcriptional activation induced by PPAR through a PPRE was significantly suppressed by cotransfection of TR in transient transfection assays. The inhibition, however, was not affected by adding 3,5,3'-triiodo-L-thyronine (T3). Furthermore, the inhibition was not observed in cells cotransfected with retinoic acid receptor or vitamin D3 receptor. The inhibitory action by TR was lost by introducing a mutation in the DNA binding domain of TR, indicating that competition for DNA binding is involved in the molecular basis of this functional interaction. Gel shift assays revealed that TRs, expressed in insect cells, specifically bound to the 32P-labeled PPRE as heterodimers with the retinoid X receptor (RXR). Both PPAR and TR bind to PPRE, although only PPAR mediates transcriptional activation via PPRE. TR.RXR heterodimers are potential competitors with PPAR.RXR for binding to PPREs. It is concluded that PPAR-mediated gene expression is negatively controlled by TR at the level of PPAR binding to PPRE. We report here the novel action of thyroid hormone receptor in controlling gene expression through PPREs.

Animals↗

Two types of stretch-activated channels coexist in the rabbit corneal epithelial cell.

Ion channels contribute to the regulation of cellular function through control of the membrane potential and intracellular concentration of various ions. We examined stretch-activated channels in the corneal epithelial cell. Patch clamping was applied to enzymatically dissociated corneal epithelial cells to characterize their stretch-activated ion channels. The plasma membrane was stretched by applying suction to the patch pipette in cell-attached or inside-out patch configuration. The ion selectivity, voltage-dependence, and stretch-dependence were examined. Two kinds of stretch-activated channel events were observed; the previously-reported large conductance (L) channel and a novel small conductance (S) channel. The probability of recording L vs. S channels in the cell-attached configuration was about 2:1. The L channel was potassium selective with single channel conductance (gamma) of about 160 pS under the symmetrical (150 mm K+) solution. The S channel was permeable to Na+ and K+ with gamma of about 20 pS under the same conditions. Both L and S channels showed little activity in the absence of suction applied to the recording pipette. Channel activity was evoked by suction (negative pressure) stronger than -20 mmHg in both channels. The open probability (Po) and the mean current increased in proportion to further applied stretch and did not saturate for applied suction as strong as -80 mmHg, the pressure at which the gigaseal started to break. Thus, two types of stretch-activated channels coexist in corneal epithelial cells; a potassium-selective L channel and non-selective S channel. The contribution of these channels to the membrane potential is discussed.

Animals↗

Thyroid cancer in children: report of three cases and a review of the Japanese literature.

We experienced three cases of thyroid cancer in children less than 15 years of age between 1982 and 1995. We herein present these three cases with a review of 141 reported cases of childhood thyroid cancer in Japan. Our patients were 6, 13, and 14 years old. The patients, all girls, were diagnosed as having thyroid cancer based on diagnostic imaging. One of them was also diagnosed by a fine-needle aspiration biopsy (FNAB). One of them underwent subtotal thyroidectomy, and the other two underwent lobectomy. Modified neck dissections were performed on all three. Pathologically, the tumors were all papillary carcinomas. Multiple lymph node metastases were present in all patients. However, the postoperative courses have been good, and there have been no signs of recurrence, 10, 8, and 2 years after their respective operations. In 144 reported cases of childhood thyroid cancer in Japan including ours, the youngest patient was a 2-year-old boy, and the female to male ratio was 2.1:1. FNAB was performed in 25 cases, and 23 (92%) of the tumors were diagnosed as malignant. Histologically, 76% were papillary carcinoma and 20% follicular carcinoma. At operation, lymph node metastases were found in 80% of the cases, and lung metastases in 17%. For treatment, 88% of the patients received a more extensive operation than a lobectomy. Of the 144 patients, 8 died.

Adolescent↗

Endoscopic follow-up study of development of gastric antral vascular ectasia associated with liver cirrhosis.

Gastric antral vascular ectasia is an important cause of chronic gastrointestinal blood loss. However, its development and progression have not yet been clarified. We investigated its early lesions and progression by reviewing endoscopic films of five patients with gastric antral vascular ectasia followed for liver cirrhosis. In all patients, early findings were prepyloric red spots. In two patients, anemia due to gastrointestinal bleeding was already observed when vascular lesions were confined to the distal antrum. In the other three patients, anemia was observed 1-2 years after they showed a diagnostic pattern of gastric antral vascular ectasia. The vascular lesions gradually thickened and extended throughout the antrum, with the complete picture shown in 1.5-5 years. The pattern of distribution was classified into three types: diffuse spotty, diffuse confluent, and striped. These types could be predicted before the complete formation. Gastric antral vascular ectasia associated with liver cirrhosis started as prepyloric red spots and extended to the proximal antrum in various ways and varying time courses of less than 5 years; this entity may cause hemorrhage even in the early stage.

Aged↗