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Biomedical subjects

K Kishi

Publications and source records attributed to K Kishi.

At least 127 records · Page 7Linked to original sources

Changes in squamous cell carcinoma-related antigen levels before and after hemodialysis in relation to the model of dialyzer employed.

OBJECTIVE: Although tumor marker levels in blood become elevated after hemodialysis as a result of the amount of fluid removed, serum squamous cell carcinoma-related antigen (SCC) levels have not been always reported to increase after hemodialysis. The purpose of this report is to determine whether there is a difference between the change of serum SCC levels before and after hemodialysis according to the model of dialyzer employed. PATIENTS AND METHODS: In ninety-four patients on hemodialysis (50 cases of diabetic nephropathy and 44 cases of glomerulonephritis), we examined serum SCC levels before and after hemodialysis. RESULTS: There was no overall difference between SCC levels before and after hemodialysis (3.2+/-1.5 ng/ml vs 3.3+/-1.7 ng/ml, p=0.2381). In patients treated with a cellulosic type membrane dialyzer (n=73), SCC levels after hemodialysis were higher than those before hemodialysis (3.7+/-1.7 ng/ml vs 3.5+/-1.5 ng/ml, p=0.0495). In patients treated with a synthetic type membrane (n=21), SCC levels after hemodialysis decreased when compared to those before hemodialysis (1.9+/-0.7 ng/ml vs 2.2+/-0.8 ng/ml, p=0.0018) and in all patients, the SCC levels after hemodialysis were lower than, or equal to, those before hemodialysis. CONCLUSION: The results suggest that the decline in serum SCC levels during hemodialysis treated with synthetic type membrane of dialyzers, concealed the increased SCC levels in hemoconcentration.

Antigens, Neoplasm↗

Molecular cloning of cDNA encoding Xenopus laevis deoxyribonuclease I.

A 1200-bp cDNA encoding Xenopus laevis deoxyribonuclease I (X. laevis DNase I) was constructed from the total RNA of a X. laevis pancreas using a rapid amplification of cDNA ends method. When the cDNA was transiently transfected into COS-7 cells, the recombinant polypeptide exhibited similar enzymological properties to those of the native pancreatic DNase I. The recombinant enzyme was considerably more labile than most other vertebrate DNase I enzymes. The X. laevis DNase I polypeptide was larger than any other known vertebrate DNase I, containing a unique Cys-rich stretch of 68 or 70 amino acid residues at the carboxyl terminus, and it had less well conserved binding sites for the Ca2+, G-actin and DNA, and two DNase I signature motifs. These alterations might account for its heat instability.

Amino Acid Sequence↗

[Optimal dose of indocyanine-green injected from the peripheral vein in cardiac output measurement by pulse dye-densitometry].

Cardiac output is measured by pulse dye-densitometry using indocyanine-green (ICG). This cardiac output is estimated by correlating with the cardiac output measured by pulmonary artery catheter using thermodilution method. Twenty-four patients scheduled for elective cardiovascular surgeries under general anesthesia were studied. The pulse dye-densitometry monitoring system used was DDG-2001 (Nihon Kohden, Japan). In group A (13 patients: 19 times), ICG was administered from the peripheral vein as bolus doses of 5, 10 or 20 mg (5 mg.ml-1 water solution). In group B (11 patients: 12 times), ICG was administered from the peripheral vein as bolus doses of 20, 10 or 5 mg (5 mg.ml-1 water solution). The correlation (Pearson's correlation coefficient) and precision (the method proposed by Bland and Altman) compared with cardiac output measured by pulmonary artery catheter were examined. Better correlation and precision were recognized after 20 mg ICG injection than 5 or 10 mg ICG injection. In conclusion, the measurement of cardiac output by pulse dye-densitometry with peripheral vein ICG injection was useful using a bolus dose of ICG 20 mg.

Aged↗

Activation of G-protein coupled fMLP or PAF receptor directly triggers glucose transporter type 1 (GLUT1) translocation in Chinese hamster ovary (CHO) cells stably expressing fMLP or PAF receptor.

The chemoattractants, fMLP and PAF, stimulate glucose uptake in phagocytes to obtain an energy source for host defense. Glucose uptake in phagocytes is mainly regulated via glucose transporter type 1 (GLUT1). To examine molecular mechanisms of facilitated glucose uptake in response to fMLP or PAF, we established CHO cells stably expressing fMLP or PAF receptor with c-myc epitope tagged GLUT1 which could immunologically detect GLUT1 on the cell surface. In the CHO cells, both fMLP and PAF directly triggered GLUT1 translocation from the intracellular pool to the cell surface, and stimulated glucose uptake. Therefore, in phagocytes, we propose that fMLP and PAF also trigger GLUT1 translocation to stimulate glucose uptake as an energy source for host defense.

Amino Acid Sequence↗

Overexpression of wild-type Akt1 promoted insulin-stimulated p70S6 kinase (p70S6K) activity and affected GSK3 beta regulation, but did not promote insulin-stimulated GLUT4 translocation or glucose transport in L6 myotubes.

We have developed a simple, direct and sensitive method to detect GLUT4 on the cell surface. Using this system, we found that PI3-kinase plays a key role in the signaling pathway of insulin-stimulated GLUT4 translocation. One of the down stream effectors of PI3-kinase is serine-threonine kinase Akt (protein kinase B, RAK-PK), but the involvement of Akt in insulin-stimulated GLUT4 translocation is controversial. To investigate whether Akt1 regulates insulin-stimulated GLUT4 translocation and glucose uptake in L6 myotubes, we established L6 myotubes stably expressing c-myc epitope-tagged GLUT4 (GLUT4myc) and mouse wild type (WT) Akt1. We found that overexpression of WT Akt1 promoted insulin-stimulated p70S6 kinase (p70S6K) activity and increased the basal activity of GSK3 beta, but did not promote insulin-stimulated GLUT4 translocation or glucose uptake. These data supported the result that Akt is not a main signaling molecule to transmit the signal of insulin-stimulated GLUT4 translocation or glucose uptake from insulin-activated PI3-kinase.

Amino Acid Sequence↗

[Long-term results of TIPS].

The long-term results of transjugular intrahepatic portosystemic shunt(TIPS) were analyzed in 48 patients between February 1992 and December 1998, for treatment of esophageal varices and ascites caused by portal hypertension. The procedure was successful in 42 patients. Portal vein pressure was reduced from 29 mmHg +/- 7.9 to 19 mmHg +/- 7.3 immediately after TIPS and to 17 mmHg +/- 6.5 one year later. Varices were controlled in 82% (23/28) of patients after one year and in 78% (7/9) of patients after five years. Ascites disappeared or decreased in 79% (11/14) after one year. Primary shunt patency was 12%, with a secondary patency rate of 79% after five years. The overall incidence of new or worsened encephalopathy was 31% (13/42). Long-term follow-up showed one-, three-, and five-year survival rates of 82%, 68%, and 59%, respectively. TIPS is an effective means of lowering portal hypertension, and it controls varices and ascites with little risk of hepatic encephalopathy.

Adult↗

[Therapeutic effect of TAE in patients with hepatocellular carcinoma using color Doppler imaging with intravenous ultrasound contrast agent].

We evaluated the therapeutic effect of TAE in 9 nodules with hepatocellular carcinoma (HCC) using color Doppler flow imaging with an intravenous ultrasound contrast agent. The intratumoral color signal enhancement that was detected in 7 nodules resulted in complete disappearance after TAE. The other 2 nodules without color signal enhancement showed well-differentiated HCC with fatty degeneration on histological study. The intratumoral enhancement noted in dynamic MRI in 7 of the 9 nodules resulted in complete disappearance after TAE. Color Doppler flow imaging with an intravenous contrast agent is a promising method for assessing the therapeutic effect of TAE.

Aged↗

[Recent studies on anti-angiogenesis in cancer therapy].

Angiogenesis is known to be a critical process for the tumor growth and metastasis. There are many indigenous role-players in tumor angiogenesis and anti-angiogenesis, where tumor-host interaction may work. A lot of agents with anti-angiogenic activity have been developed for anti-cancer treatment. Several agents including Marimastat, Primostat, Neovastat, Bay-12-9566m, Interferon-alpha, SU101, retinoids, and IM862, are/were under phase-three study. There are still many future-promising results of basic or clinical studies on inhibitors of MMPs, and inhibitors of VEGF/R, Endostatin, somatostatin analogues, COX-2 inhibitors, and others. Most of the combination treatments of antiangiogenetic agent and conventional anticancer agents therapy, or radiation therapy as we reported, showed relatively small or minute increase in toxicity of these cytotoxic treatments.

Angiogenesis Inhibitors↗

[Sarcoidosis in a man and his identical twin sons].

Sarcoidosis is known to be a disease characterized by high familial aggregations. We reported on the genealogy of sarcoidosis in a man and his identical twin sons. The patient we encountered was a 49-year-old man admitted to our hospital because of abnormal chest X-ray findings observed during a medical checkup. Cervical and hilar lymph nodes were swollen on both sides, and lesions were observed in the right lung field. Biopsy specimens from cervical lymph nodes disclosed epithelioid cell granuloma without caseous necrosis. A diagnosis of sarcoidosis was made. The disease had also been diagnosed in the patient's identical twin sons 2 years earlier. They had been successfully treated and no recurrence has been observed. HLA typing disclosed that the father and his twin sons had identical A 33 (19), B 44 (12), DR 2, and DR 12 genes. This finding suggested that genetic factors are involved in the onset of this disease.

Adult↗

[Chronic cough caused by gastroesophageal reflux].

We reported a case of chronic cough due to gastroesophageal reflux (GER). The patient was a 29-year-old woman who had suffered from persistent chronic cough for more than 3 years. She had been treated with high doses of inhaled steroids, oral bronchodilators, and oral corticosteroids on a presumed diagnosis of asthma. However, her cough was not alleviated by these treatments, and the patient was referred to our hospital. She did not exhibit typical GER symptoms except for belch. Although esophagoscopy did not disclose reflux esophagitis, esophageal pH monitoring revealed acid reflux 7 to 8 times higher than the reference value. The patient was treated with a proton-pump inhibitor, which markedly alleviated her cough. Chronic cough due to GER was diagnosed. Although the incidence of chronic cough due to GER was thought to be rare in Japan, the findings in our case report underscored the importance of this association to the differential diagnosis of chronic cough.

Adult↗

[Mixed connective tissue disease-associated interstitial pneumonia complicated by pneumomediastinum during prednisolone therapy].

A 59-year-old woman was admitted to our hospital with exertional dyspnea. Linear and reticular opacities in the middle and lower fields of both lungs were observed on chest roentgenograms and chest computed tomograms (CT). The presence of anti RNP-antibody and Raynaud's phenomenon, sclerosis of the fingers, and leukopenia yielded a diagnosis of mixed connective tissue disease associated with interstitial pneumonia. The symptoms and lung involvement were alleviated after the administration of prednisolone (40 mg/day). However, the patient experienced the sudden onset of dyspnea during pulmonary function tests. A chest X-ray film disclosed mediastinal air around the left pulmonary artery, and a chest CT scan demonstrated some blebs in the left lower lung field. After tapering the dosage of prednisolone in 5 mg increments per week, the pneumomediastinum disappeared without treatment. The clinical features and laboratory data findings suggested the patient's interstitial pneumonia was associated with systemic lupus erythematosus rather than with progressive systemic sclerosis or dermatomyositis. The pneumomediastinum may have been due to the rupture of blebs secondary to interstitial pneumonia during pulmonary function tests or as a result of steroid therapy.

Acute Disease↗

[A clinicopathological study of pulmonary cryptococcosis--chest CT and pathologic correlation].

We reviewed the clinicopathological features in 12 patients (7 males and 5 females; mean age 54 yr) with pulmonary cryptococcosis. Eleven of the patients were asymptomatic and the disease was detected by chest radiograph abnormalities. The underlying systemic disease had been diagnosed as diabetes mellitus in two. Chest CT scans showed a solitary nodule in 9 of the 12 patients, multiple nodules in 2, and infiltration in 1. The nodular diameter was less than 2 cm in 10 of the 12. All nodules were located in the subpleural region. On the chest CT, cavitary nodules, scattered nodules, or both, and spiculated nodules were difficult to distinguish from pulmonary tuberculosis and primary lung cancer, respectively. According to McDonnell's pathological classification of pulmonary cryptococcosis, the resected 8 lungs revealed peripheral pulmonary granuloma in 5 and granulomatous pneumonia in 3. It is important to perform a pathological examination for the diagnosis of pulmonary cryptococcosis to avoid misdiagnosis as lung cancer or pulmonary tuberculosis.

Adult↗

Inhibition of ATRA-induced myeloid differentiation in acute promyelocytic leukemia by a new protein tyrosine phosphatase inhibitor, 3,4-dephostatin.

We previously reported that the expression and the activity of SHP-1, a non-transmembrane protein tyrosine phosphatase (PTPase) increased during myeloid differentiation of an acute promyelocytic leukemia cell line (HT93) induced by all-trans retinoic acid (ATRA). To examine whether inhibition of SHP-1 activity attenuates myeloid differentiation, we used a new PTPase inhibitor, 3,4-dephostatin, and studied its effect on myeloid differentiation. Suppressive effects on immunoprecipitated SHP-1 phosphatase activity and myeloid cell differentiation were detected. These results suggest that SHP-1 is a substrate for 3,4-dephostatin, and that SHP-1 PTPase activity is closely related to myeloid differentiation.

Cell Differentiation↗

CDC25B and p53 are independently implicated in radiation sensitivity for human esophageal cancers.

Ionized radiation leads to G1 arrest and apoptosis by a p53-dependent pathway and G2-M arrest through a p53-independent pathway. In this study, we evaluated the role of cell cycle-regulating molecules in the sensitivity of cancer cells for radiation therapy. Forty-seven patients with squamous cell carcinomas of the esophagus had undergone radiation therapy, followed by surgical resection. They were classified as sensitive to radiation (SR, 14 cases) with no residual tumor in the surgical specimen or as resistant to radiation (RR, 33 cases) with viable residual tumors. Their preradiation biopsy samples were immunohistochemically investigated for the expressions of cell cycle-related molecules, including p53, CDC25A, CDC25B, cyclin D1, cyclin B1, and Ki-67. p53 expression was negative in 71% (10 of 14) of SR and positive in 91% (30 of 33) of RR. The association was strong between high radiation sensitivity and negative p53 expression (P < 0.0001). CDC25B, which is not expressed in normal epithelium but is in the cytoplasm of esophageal cancers, was strongly expressed (2+) in 46% (6 of 14) of SR and in 6% (2 of 23) of RR. Thus, the sensitivity for radiation therapy was significantly correlated with CDC25B overexpression. With respect to CDC25A, cyclin D1, cyclin B1, and Ki-67, no statistically significant differences were found in their expressions between SR and RR tumors. p53 and CDC25B expressions showed no significant associations, and multivariate analysis revealed that both p53 and CDC25B are significant independent markers for predicting radiation sensitivity. CDC25B was revealed to be a novel predictor of radiation sensitivity in esophageal cancers. Because CDC25B is an oncogene, which affects G2-M progression, these results suggest the importance of a p53-independent G2-M checkpoint in radiation therapy.

Antimetabolites, Antineoplastic↗

C/EBPbeta and GATA-1 synergistically regulate activity of the eosinophil granule major basic protein promoter: implication for C/EBPbeta activity in eosinophil gene expression.

Eosinophil granule major basic protein (MBP) is expressed exclusively in eosinophils and basophils in hematopoietic cells. In our previous study, we demonstrated a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription. Further analysis of the MBP promoter region identified a C/EBP (CCAAT/enhancer-binding protein) consensus binding site 6 bp upstream of the functional GATA-binding site in the MBP gene. In the cell line HT93A, which is capable of differentiating towards both the eosinophil and neutrophil lineages in response to retinoic acid (RA), C/EBPalpha mRNA expression decreased significantly concomitant with eosinophilic and neutrophilic differentiation, whereas C/EBPbeta expression was markedly increased. Electrophoretic mobility shift assays (EMSAs) showed that recombinant C/EBPbeta protein could bind to the potential C/EBP-binding site (bp -90 to -82) in the MBP promoter. Furthermore, we have demonstrated that both C/EBPbeta and GATA-1 can bind simultaneously to the C/EBP- and GATA-binding sites in the MBP promoter. To determine the functionality of both the C/EBP- and GATA-binding sites, we analyzed whether C/EBPbeta and GATA-1 can stimulate the MBP promoter in the C/EBPbeta and GATA-1 negative Jurkat T-cell line. Cotransfection with C/EBPbeta and GATA-1 expression vectors produced a 5-fold increase compared with cotransfection with the C/EBPbeta or GATA-1 expression vectors individually. In addition, GST pull-down experiments demonstrated a physical interaction between human GATA-1 and C/EBPbeta. Expression of FOG (riend ATA), which binds to GATA-1 and acts as a cofactor for GATA-binding proteins, decreased transactivation activity of GATA-1 for the MBP promoter in a dose-dependent manner. Our results provide the first evidence that both GATA-1 and C/EBPbeta synergistically transactivate the promoter of an eosinophil-specific granule protein gene and that FOG may act as a negative cofactor for the eosinophil lineage, unlike its positively regulatory function for the erythroid and megakaryocyte lineages.

Base Sequence↗

Maximizing therapeutic gain with gemcitabine and fractionated radiation.

PURPOSE/OBJECTIVE: The nucleoside analogue gemcitabine inhibits cellular repair and repopulation, induces apoptosis, causes tumor growth delay, and enhances radiation-induced growth delay. After single doses of drug and radiation, maximum enhancement of tumor response was obtained when gemcitabine preceded radiation by at least 24 h. Conversely, the cellular radioresponse of the normal gastrointestinal epithelium was slightly protected when gemcitabine and radiation were separated by 24 h. This differential response created a time frame within which therapeutic gain could be maximized. In our present investigation, we sought to define the most therapeutically beneficial scheme of gemcitabine administration when combined with fractionated radiotherapy. METHODS AND MATERIALS: C3Hf/Kam mice were given identical drug and radiation schedules of administration, and both normal tissue (jejunal mucosa) and tumor (Sa-NH) responses were measured. Irradiation was given once per day for 5 days in normal tissue and tumor growth delay studies and twice per day for the tumor cure endpoint. A total dose of 25 mg/kg gemcitabine was given i.p. in 1 of 3 schedules: a single dose of 25 mg/kg 24 h before the start of fractionated irradiation, 12.5 mg/kg 24 h before the first and third radiation doses, or 24 h before each of 5 radiation doses. Groups of mice bearing 7- or 8-mm diameter tumors were treated with gemcitabine alone or in combination with fractionated irradiation under ambient or hypoxic conditions. The survival response of the jejunal mucosa was quantified by the microcolony assay and histologically by quantifying apoptosis, mitosis, S-phase fraction, and crypt cellularity. RESULTS: For tumor growth delay, dose-modifying factors (DMFs) were similar (1.34-1.46) for all 3 schedules of drug administration. In contrast, the response of the jejunum was strongly dependent on the schedule of gemcitabine administration. A single dose of gemcitabine before the start of fractionated radiotherapy resulted in slight radioprotection (DMF 0.96). Two doses and 5 daily doses of gemcitabine enhanced radiation response by factors of 1.09 and 1.23, respectively. Major factors affecting the response of the jejunal mucosa were apoptotic death of S-phase cells exposed to gemcitabine and cell cycle synchrony of surviving cells. Tumor reoxygenation was found to be a major mechanism for tumor radioenhancement, in addition to those reported earlier. CONCLUSION: All 3 schedules of drug administration produced therapeutic gain; however, when gemcitabine was given more than once in a 5-fraction radiation treatment schedule, normal tissue toxicity increased. The highest therapeutic gain (1.4) was achieved by giving a single dose of gemcitabine (25 mg/kg) 24 h before the start of fractionated radiotherapy.

Animals↗

A new allele, DNASE1*6, of human deoxyribonuclease I polymorphism encodes an Arg to Cys substitution responsible for its instability.

A new allele, DNASE1*6, of human deoxyribonuclease I (DNase I) has been discovered by isoelectric focusing: its gene product has the most cathodic pI of the six electrophoretic variants. Results of DNA sequencing, mismatched PCR-restriction fragment length polymorphism, and transient transfection of the variant construct showed that the mutant was caused by a C-T transition at nucleotide position 1826, resulting in an Arg to Cys substitution at amino acid position 185 of the mature enzyme. The variant isoenzyme, expressed in COS-7 cells, was more labile than the other types. Instability and an increase in the pI value of the variant suggest that a structural alteration, perhaps due to aberrant formation of a disulfide bond, could occur in the enzyme.

Alleles↗