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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 199 records · Page 11Linked to original sources
PubMed2000

PSK and OK-432-induced immunomodulation of inducible nitric oxide (NO) synthase gene expression in mouse peritoneal polymorphonuclear leukocytes and NO-mediated cytotoxicity.

We investigated whether PSK (a polysaccharide from the mycelia of Coriolus versicolor) or OK-432 (a streptococcal preparation) can up-regulate inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production in mouse peritoneal polymorphonuclear leukocytes (PMNs). Six hrs after intraperitoneal injection of mice with PSK (2,500 microg/mouse) or OK-432 (100 microg/mouse), mouse peritoneal PMNs were restimulated with PSK (500 microg/ml) or OK-432 (10 microg/ml) plus 100 U/ml of mouse interferon-gamma (IFN-gamma) in vitro. Northern blot analysis showed strong synergism between both PSK and OK-432 and IFN-gamma for the induction of iNOS gene expression. NO production by PMNs was increased up to 20 microM (2 microM/10(6) PMNs/24 hrs) as measured by the Griess reagent method when PMNs were restimulated with PSK or OK-432 plus IFN-gamma for 24 hrs, although tumor cell killing was not detected. NO concentrations of more than 80 microM were required for P815 tumor cell killing. These results suggest that PMNs produce NO after stimulation with PSK or OK-432 in combination with IFN-gamma and may regulate the immune system in vivo, although the NO production induced by these agents is insufficient for tumor cell killing in vitro.

Adjuvants, Immunologic↗
PubMed2000

[Worsened orthostatic hypotension due to levodopa administration in a case of Parkinson's disease].

A 70-year-old woman began to experience gait disturbance in 1995, followed by the appearance of action tremor of the left hand in 1996. This tremor was subsequently noted in the right hand. Her doctor initially diagnosed Parkinson's disease and administered amantadine and levodopa. The gait disturbance and tremor improved. However, she stopped taking the medication and her symptoms worsened in April, 1998. She was admitted to our hospital, and showed rigidity and action tremor predominantly on the left side, frozen gait, postural reflex disturbance and orthostatic hypotension. Following levodopa administration, her UPDRS score improved from 61.3 +/- 1.2 (mean +/- SD) to 41.7 +/- 5.4. However, she experienced a greater decrease in systolic blood pressure following administration upon standing, from 12.5 +/- 5.8 mmHg to 17.8 +/- 9.2 mmHg. Thus, although levodopa administration led to an improvement in rigidity, tremor and akinesia, her orthostatic hypotension worsened. Based on the present results clinicians should be aware of the potential of worsened orthostatic hypotension when prescribing levodopa to treat Parkinson's disease.

Aged↗
PubMed2000

Nuclear accumulation of p53 protein and apoptosis induced by various anticancer agents, u.v.-irradiation and heat shock in primary normal human skin fibroblasts.

Relationship between nuclear accumulation of p53 protein and apoptosis induced by both DNA damaging agents (ultraviolet-irradiation and anticancer agents) and heat shock in normal human skin fibroblasts was investigated. Nuclear accumulation of p53 protein and apoptosis were induced dose-dependently by u.v. -irradiation and anticancer agents. Regarding heat shock treatment, intensive nuclear accumulation of p53 protein was induced by treatment at 43 degrees C for 45 min, but, apoptotic cells were never detected. These results indicated that accumulation of p53 protein and apoptosis induced by DNA damaging agents were considered to have a close relationship and the functions of induced p53 protein are different depending on the stimulating factor.

Antineoplastic Agents↗
PubMed2000

[A case of advanced gastric cancer (type 3) with pyloric stenosis, multiple liver and lymph node metastases responding to UFT-E granules and lentinan].

The patient was a 80-year-old male with advanced gastric cancer (Type 3) accompanied by multiple liver and lymph node metastases. Histological findings in the stomach showed poorly differentiated adenocarcinoma. He had nausea, vomiting and anorexia due to pyloric stenosis, and was treated with 600 mg of UFT E granules/day orally for 5 consecutive days followed by 2 drug-free days (weekly-5 method), and 2 mg of lentinan intravenously twice a week. After 4 weeks of treatment, the primary tumor and metastatic lesions of the liver and lymph nodes were markedly reduced. His symptoms had completely disappeared along with lessening of the pyloric stenosis after 6 weeks of treatment. The patient survived for 7 months in a state of CR and PR. The adverse effects were very mild and negligible. A weekly-5 method of UFT, in comparison with conventional daily administration, may induce maximal antitumor effects with minimal adverse effects.

Adenocarcinoma↗
PubMed2000

Multifocal electroretinogram in occult macular dystrophy.

PURPOSE: Occult macular dystrophy (OMD) is an unusual macular dystrophy presenting with an essentially normal fundus and fluorescein angiography but with progressive central visual loss. The authors studied the function of local retinal areas in the posterior pole of patients with OMD using multifocal electroretinograms (ERGs). METHODS: Multifocal ERGs were recorded using the Visual Evoked Response Imaging System with 61 hexagonal elements within a visual field of 30 degrees radius from 8 OMD patients and 20 age-matched, normal subjects. The amplitudes and implicit times of the patients and normal control subjects were compared at the various retinal eccentricities. RESULTs. The amplitudes of the multifocal ERGs in the OMD patients were markedly reduced in the central 7 degrees of the fovea. The difference of the ERG amplitudes between OMD and normal subjects became smaller toward the peripheral retina. Most OMD patients had slight but significantly delayed implicit times across the whole testing field, and the differences between the OMD and the normal subjects did not change with retinal eccentricity. CONCLUSIONS: Our results for multifocal ERG amplitudes support the idea that OMD patients have localized retinal dysfunction distal to the ganglion cells in the central retina. The delayed implicit times across the whole test field suggest that the retinal dysfunction has a broader boundary than expected by ERG amplitudes and psychophysical perimetric results.

Adult↗
PubMed2000

Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus.

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies including squamous cell carcinomas (SCCs) of the esophagus, but little is known about COX-2 expression in premalignant esophageal squamous dysplasia. To elucidate the role of COX-2 in esophageal carcinogenesis, we examined the expression of this enzyme in normal squamous epithelium (n = 42), squamous dysplasia [high-grade dysplasia (HGD, n = 41; low-grade dysplasia (LGD, n = 33)]; carcinoma in situ (n = 16), mucosal invasive carcinoma (n = 18), and advanced SCC (n = 45). Immunohistochemistry showed a significantly high COX-2 expression in HGD compared with other lesions. The COX-2 score, an index determined by intensity and positivity of COX-2 staining (maximum 3.0), was 0.29 +/- 0.04 in normal esophagus, 1.75 +/- 0.11 in LGD, 2.89 +/- 0.05 in HGD, 2.17 +/-0.18 in CIS, 1.95 +/- 0.22 in mucosal invasive carcinoma, and 1.81 +/- 0.08 in advanced SCC. Results of reverse transcription-PCR assays confirmed those obtained by immunohistochemistry. COX-2 expression correlated with proliferation activity assessed by the proliferating cell nuclear antigen index in dysplastic lesions (P = 0.001) but not in SCCs. COX-2 expression in SCC did not correlate with various clinicopathological parameters including prognosis. Our results indicate that COX-2 is a sensitive marker for HGD and suggest that COX-2 may be involved in early stages of squamous carcinogenesis of the esophagus.

Antibodies, Monoclonal↗
PubMed2000

Expression of interferon alpha/beta receptor in human hepatocellular carcinoma.

Interferon-alpha (IFNalpha) plays a crucial role in the antiproliferation and immunoregulatory activity through the specific cell surface receptor, interferon-alpha/beta receptor (IFNalpha/betaR). We examined the immunohistochemical expression of IFNalpha/betaR in 91 hepatocellular carcinoma (HCC), HCV-related chronic hepatitis (n=38) and cirrhosis (n=53), dysplastic nodules (n=5), and normal liver (n=9). The level of IFNalpha/betaR increased in chronic hepatitis and cirrhosis compared with normal liver. All the dysplastic nodules showed moderate or high expression. In HCCs, 26% (24/91) of patients showed high IFNalpha/betaR expression while the remaining 38% (35/91) showed moderate, and 35% (32/91) no or faint expression. Clinicopathological survey demonstrated a significant correlation between IFNalpha/betaR expression and differentiation of carcinoma (P=0.0008) although there was no correlation between IFNalpha/betaR expression in HCC and survival or disease-free survival. Thus, IFNalpha/betaR was expressed not only in chronic hepatitis or liver cirrhosis but in HCC and its expression was significantly correlated with tissue differentiation of carcinoma.

Blotting, Western↗
PubMed2000

Efficacy of common antiseptics against mycobacteria.

SETTING AND OBJECTIVE: Antiseptics are frequently used to prevent mycobacterial infection; however, the reported activities of a number of antiseptics against mycobacteria are not always consistent. The aim of this study was to determine those antiseptics that are useful against mycobacteria. DESIGN: Evaluation of antiseptic activity against mycobacteria in vitro. RESULTS: The effects of different antiseptics on mycobacteria (Mycobacterium avium, M. kansasii and M. tuberculosis) were examined. At concentrations of 0.05%, povidone-iodine (PVP-I) killed 99% or more of all strains tested within 15 seconds, while 0.5% chlorhexidine gluconate and 0.1% benzalkonium chloride showed no bactericidal activity against mycobacteria. M. kansasii and M. tuberculosis were killed after exposure to cresol for 60 seconds at concentrations of 1.0%, but M. avium was unaffected even after 60 seconds. While M. kansasii and M. tuberculosis were killed by treatment with 2.0% glutaraldehyde for 5 minutes, M. avium was highly resistant to this agent. CONCLUSION: PVP-I seems to be a useful antiseptic against mycobacteria. The measured activity of antiseptics should be interpreted carefully, due to the potential for interference by artifacts.

Anti-Infective Agents, Local↗
PubMed2000

[Clinical evaluation of cases with massive ascites accumulation after discontinuation of CAPD: an attempt to establish the concept of the pre-sclerosing encapsulating peritonitis(pre-SEP) state].

Sclerosing encapsulating peritonitis(SEP) is a most serious complication of continuous ambulatory peritoneal dialysis(CAPD). Although the criteria of diagnosis and guidelines for therapy of SEP have been proposed by the Japanese SEP Study Group already, SEP is refractory to treatment when the disease process is complete. It is important to detect the latent phase of SEP(pre-SEP state) in order to treat patients at an early stage. We evaluated the characteristics of ascites in four patients with massive ascites accumulation after discontinuation of CAPD. Age and the duration of CAPD of the subjects were 53.3 +/- 9.7 years and 126.5 +/- 6.8 months, respectively. However, the patients were withdrawn from CAPD because of peritonitis or ultrafiltration failure. We also followed cytokines and parameters of collagen metabolism of ascites in two patients during adrenocorticosteroid therapy and conducted a histopathological evaluation of the peritoneum of an autopsy case who had died of pneumonia. Ascites seems to be exudative because of the high concentration of protein, cytokines and parameters of collagen metabolism such as interleukin-1 beta, interleukin-6, transforming growth factor-beta 1, procollagen 3 peptide, and type IV collagen 7S, the levels of which were 21.3 +/- 9.3 pg/ml, 8,153 +/- 7,327 pg/ml, 6.7 +/- 3.6 ng/ml, 89.3 +/- 67.8 U/ml, and 59.0 +/- 36.2 ng/ml, respectively. The histopathological findings of the peritoneum from the autopsy case showed dense fibrous tissue permeated with inflammatory infiltration and widespread infiltration of fibrin. These findings suggested that the peritoneum was inflamed when massive ascites accumulated. The amount of ascites and concentration of cytokines and parameters of collagen metabolism of ascites diminished during adrenocorticosteroid therapy. We concluded that massive and refractory accumulation of ascites appearing after the discontinuation of CAPD should be regarded as a sign of the pre-SEP state, and prophylactic treatment should be started at this stage of disease.

Adult↗
PubMed2000

Differences in 20q13.2 copy number between colorectal cancers with and without liver metastasis.

Frequent gains of 20q have been identified recently in many neoplasias, including breast, bladder, ovarian, pancreatic, and colon cancers. A high level of 20q13.2 amplification is associated with poor prognosis in breast cancer. We investigated the copy number of the 20q13.2 region including the ZNF217 oncogene in 17 nonmetastatic colorectal cancers (CRCs), 18 primary CRC tumors with liver metastasis, and 18 metastatic lesions by two-color fluorescence in situ hybridization to evaluate the significance of an increased copy number of 20q13.2 in CRC, especially in those cases with liver metastasis. The frequency of increased relative copy number of the 20q13.2 region was higher in primary and liver metastatic lesions of CRC than in CRC lesions without liver metastasis. In particular, a high-level increase (>3.0-fold) in the relative copy number of 20q13.2 was observed in 2 of 18 (11%) primary CRC lesions with liver metastasis, 7 of 18 (39%) liver metastatic lesions, and in none of the cases of primary CRC without liver metastasis. The absolute and relative copy number of chromosome 20q13.2 was higher in CRCs with metastasis than in CRCs without metastasis. The percentage of cells with high-level 20q13.2 amplification was also higher in both lesions with metastasis per specimen than without metastasis. Our results suggest that the level of 20q13.2 amplification correlates with the metastatic potential and tumor progression of CRC. The results also suggest that 20q13.2 amplification with ZNF217 is associated with increased metastatic potential.

Chromosome Mapping↗
PubMed2000

Augmentation of antitumor activity of 5-fluorouracil by interferon alpha is associated with up-regulation of p27Kip1 in human hepatocellular carcinoma cells.

Several clinical trials have demonstrated the effectiveness of combination therapy with 5-fluorouracil (5-FU) and IFN-alpha in colon cancer, hepatocellular carcinoma (HCC), and other malignancies. In our preliminary clinical studies, we have observed outstanding effects with this combination therapy in patients with advanced HCC. However, the underlying mechanism by which IFN-alpha modulates the effects of 5-FU is unknown. We, therefore, conducted a mechanistic study using two HCC cell lines, PLC/PRF/5 and HuH7. IFN-alpha significantly enhanced the growth inhibitory effect of 5-FU in PLC/PRF/5 cells but not in HuH7 cells, and the isobolographic analysis indicated that this effect was synergistic. Flow cytometric analysis showed a delay in the progression of G0-G1 to S phase in PLC/PRF/5, and a sustained, induction of the cyclin-dependent kinase inhibitor p27-Kip1 and down-regulation of cyclin D1 was observed. Moreover, increased expression of p27Kip1 was associated with reduced CDK-2-associated kinase activity. Another difference in the two cell types was that PLC/PRF/5 expressed abundant IFN receptors, but HuH7 did not. Apoptosis assays were not helpful in explaining the mechanism. Our results suggest that the synergistic effects of 5-FU and IFN-alpha may in part be attributable to alterations in cell cycle progression via up-regulation of p27Kip1.

Apoptosis↗
PubMed2000

Retinal dysfunction in basigin deficiency.

PURPOSE: To examine the retina of basigin (Bsg) knockout mice by electrophysiological and histologic methods and thereby to determine the possible function of Bsg in phototransduction and retinal development. METHODS: Scotopic and photopic electroretinograms (ERGs) were recorded from 11 wild-type, 12 heterozygous, and 8 homozygous Bsg gene knockout mice of different ages. The retinas were also examined by histologic and immunolabeling methods. RESULTS: Bsg knockout mice of 5 to 41 weeks of age showed a decrease in the amplitude of all components of both the photopic and scotopic ERGs. In contrast, the fundus and the fluorescein fundus angiography and morphology of the retina at the light microscopic level appeared to be normal until 8 weeks of age in Bsg knockout mice. Thereafter, the length of outer segment and outer nuclear layers decreased with increasing age. Immunohistochemical analysis localized Bsg protein in a variety of cells in the retina, especially in the pigment epithelium, the upper outer plexiform layer and the inner segments of photoreceptor cells. CONCLUSIONS: The results demonstrated that both rod and cone function were severely affected from an early age by the targeted disruption of the Bsg gene. In spite of abnormal ERGs, the photoreceptor cells maintained normal morphology up to 8 weeks. Thereafter, the photoreceptor cells degenerated gradually and were almost ablated by 41 weeks.

Animals↗
PubMed2000

P23H rhodopsin transgenic rat: correlation of retinal function with histopathology.

PURPOSE: To correlate retinal functional changes with structural changes in P23H rhodopsin transgenic rats as a model of autosomal dominant retinitis pigmentosa. METHODS: P23H heterozygote (lines 1 and 3) and Sprague-Dawley control rats were studied at 4 to 29 weeks by retinal histology, electroretinogram (ERG), and a-wave transduction modeling. RESULTS: Both line 1 (faster degeneration) and line 3 (slower degeneration) showed progressive rod outer segment (ROS) shortening and outer nuclear layer (ONL) cell loss with age. ERG b-wave maximum amplitude (Vb(max)) decreased with age, but b-wave threshold remained constant within each line despite progressive ONL thinning and ROS shortening. The only exception was in line 1 at 29 weeks, which showed a slight threshold change relative to earlier ages. Va(max) and a-wave threshold changed more rapidly and were more sensitive than the b-wave in reflecting histologic degeneration. Va(max) was linearly proportional to the product of (ROS x ONL) across a two log unit range of data combined from both lines. The photopic b-wave was normal for both lines until the ONL thinned beyond 50%. Phototransduction sensitivity was normal for both lines, and dark-adaptation recovery after bleaching rhodopsin was normal. CONCLUSIONS: The P23H transgenic rat has a slow rod degeneration with initially normal cone function, consistent with clinical findings of P23H patients. However, the normal bleach recovery and the normal phototransduction sensitivity in this rat model are different from human P23H disease. a-Wave measures were more sensitive than the b-wave for tracking changes. b-Wave threshold was inexplicably poor for tracking degeneration. Although line 1 degenerated faster than line 3, the functional-structural correlates were the same. The tight linear relationship between saturated a-wave amplitude and the product of (ROS x ONL) indicates that the density of cGMP-gated channels per unit ROS plasma membrane area remains constant over a wide range of degenerations.

Animals↗
PubMed2000

[Role of nitric oxide in airway mucociliary dysfunction in diffuse panbronchiolitis].

Nitric oxide (NO) stimulates the ciliary motility of the airway epithelium, thereby assisting in the regulation of mucociliary transport in the respiratory tract. In the present study, to elucidate a possible involvement of NO in mucociliary disturbance in diffuse panbronchiolitis (DPB), we measured nasal clearance time (NCT) using the saccharin test, NO concentration in the exhaled air with a chemiluminescence analyzer, and electrolyte concentration in the sputum. Compared with healthy nonsmokers and smokers, patients with DPB showed a lower NO concentration in the exhaled air (p < 0.05), prolonged NCT (p < 0.01), and a higher Cl concentration in the sputum (p < 0.05). Among these variables, exhaled NO concentration was negatively correlated with NCT (p < 0.01) and sputum Cl concentration (p < 0.05). These results suggest that the inhibition of NO generation associated with an elevated Cl concentration in the airway surface liquid may contribute to airway mucociliary dysfunction in DPB.

Breath Tests↗
PubMed2000

[Evaluation by FDG-PET of arterial infusion chemotherapy for unresectable metastatic liver tumor].

We evaluated arterial infusion chemotherapy for unresectable metastatic liver tumor using FDG-PET and CT. A 72-year-old female patient with multiple metastatic liver tumors of rectal cancer was treated by arterial infusion chemotherapy. The tumor size decreased by chemotherapy, but there was a high uptake lesion of FDG. Three months later, tumor ingrowth was detected. FDG produces images of regional glycolytic activity, and it is a useful method of assessment of tumor viability after chemotherapy in patients with cancer.

Aged↗