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Biomedical subjects

K Kondo

Publications and source records attributed to K Kondo.

At least 163 records · Page 9Linked to original sources

[Current status and need for neurological practices from regional medical institutions].

We studied the current status of, and need for, neurological practices from regional medical institutions, including in-home services. These institutions classify patients with neurological diseases into three categories: cerebrovascular disease, intractable diseases, and other diseases with neurological symptoms. As acute and chronic neurological diseases run their course, patients require appropriate care, including diagnosis, treatment, rehabilitation, and in-home medical care. Rehabilitation is essential for patients with intractable or progressive disease because it helps to prevent progression, enhances mental health, and encourages the use of abilities that are unaffected by disease. As neurologists, we must consider how we can have a positive impact on the patient, the hospital, and the community. In Japan, the majority of patients who receive in-home medical care have neurological disorders, such as cerebrovascular disease or other intractable diseases. We have provided in-home support to 18 patients with amyotrophic lateral sclerosis who use ventilators. This year, a long-term care insurance system was instituted in Japan. Now, a support system needs to be established to provide community-based medical care, health care, and welfare services. As our population ages, we believe neurologists will play an increasingly important role in this support system.

Amyotrophic Lateral Sclerosis↗

Impact of cilostazol on clinical and angiographic outcome after primary stenting for acute myocardial infarction.

Cilostazol, an antiplatelet drug that also may inhibit smooth muscle proliferation, was given together with aspirin after primary stenting to treat patients with acute myocardial infarction. In a randomized controlled trials of 50 patients, clinical and angiographic outcome at 6 months was significantly improved with cilostazol, depicting a significantly smaller late loss and/or loss index.

Adult↗

Analysis of methanol or formic acid in body fluids by headspace solid-phase microextraction and capillary gas chromatography.

Methanol and its metabolite formic acid have been found extractable from human whole blood and urine by headspace solid-phase microextraction (SPME) with a Carboxen/polydimethylsiloxane fiber. The headspace SPME for formic acid was carried out after derivatization to methyl formate under acidic conditions. The determinations of both compounds were made by using acetonitrile as internal standard (IS) and capillary gas chromatography (GC) with flame ionization detection. The headspace SPME-GC gave sharp peaks for methanol, methyl formate and I.S.; and low background noises for whole blood and urine samples. Extraction efficiencies were 0.25-1.05% of methanol and 0.38-0.84% formic acid for whole blood and urine. The calibration curves for methanol and formic acid showed excellent linearity in the range of 1.56 to 800 and 1.56 to 500 microg/0.5 ml of whole blood or urine, respectively. The detection limits were 0.1-0.5 microg/0.5 ml for methanol and 0.6 microg/0.5 ml for formic acid for both body fluids. The within-day relative standard deviations in terms of extraction efficiency for both compounds in whole blood and urine samples were not greater than 9.8%. By using the established SPME method, methanol and formic acid were successfully separated and determined in rat blood after oral administration of methanol.

Acetonitriles↗

Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis.

Although the cyclooxygenase pathway of the arachidonic acid cascade has been suggested to play an important role in colon carcinogenesis, the molecular species of prostanoids and receptors involved have not been fully elucidated yet. We examined the development of aberrant crypt foci (ACFs), putative preneoplastic lesions of the colon, in two lines of knockout mice, each deficient in prostaglandin E receptors, EP1 and EP3, by treatment with the colon carcinogen, azoxymethane. Formation of ACFs was decreased only in the EP1-knockout mice to approximately 60% of the level in wild-type mice. Administration of 250, 500, or 1000 ppm of a novel selective EP1 antagonist, ONO-8711, in the diet to azoxymethane-treated C57BL/6J mice also resulted in a dose-dependent reduction of ACF formation. Moreover, when Min mice, having a nonsense mutation in the adenomatous polyposis coli gene, were given 500 ppm ONO-8711 in the diet, the number of intestinal polyps was significantly reduced to 57% of that in the basal diet group. These results strongly suggest that prostaglandin E2 contributes to colon carcinogenesis to some extent through its action at the EP1 receptor. Thus, EP1 antagonists may be good candidates as chemopreventive agents for colon cancer.

Animals↗

Association of a variant of the angiotensinogen gene with pure type of hypertension in pregnancy in the Japanese: implication of a racial difference and significance of an age factor.

The contribution of genetic factors to hypertension in pregnancy, including pre-eclampsia, has been well documented. The association with a common molecular variant of the angiotensinogen (AGT) gene, in which methionine (M235) is substituted for threonine (T235) at residue 235, has been reported in both Caucasians and Japanese. In the present study, we examined 115 cases of pure type of hypertension in pregnancy (PHP) and 381 normal pregnant controls in order to look for subgroups in which the AGT gene is the major factor in the PHP pathogenesis. By classification of PHP cases according to the clinical diagnosis, gravidity, and maternal age, we found significantly higher frequencies of T235 in both all PHP patients and preeclampsia/eclampsia patients than in normal controls. These results are discordant with those reported for Caucasian subjects where only a group of preeclamptic primigravidae was associated with the AGT variant, possibly indicating the existence of a racial difference. We also found that the variant frequency was significantly higher in the PHP subgroup with maternal age of 20-34 years (0.93) than in a subgroup of multigravid PHP patients age 35 years or older (0.77, P < 0.05) or in normal controls of age 20-34 years (0.76, P < 0.001). The result indicates that the AGT variant plays a significant role in hypertension in the age group 20-34 years.

Adult↗

Hemolytic and hemagglutinating activities of Prevotella intermedia and Prevotella nigrescens.

A total of 91 isolates of Prevotella intermedia or Prevotella nigrescens from subgingival sites were identified by PCR using primers specific for sequences of 16S rRNA. The hemolytic and hemagglutinating activities of the P. intermedia isolates exhibited significantly higher levels compared to those of the P. nigrescens isolates by quantitative analysis. The hemagglutinin gene (phg) was found in 23 of 26 P. intermedia isolates (88.5%), whereas it was found in only two of 44 isolates (4.5%) of P. nigrescens. The high hemolytic and hemagglutinating activities of P. intermedia may be involved in the pathogenicity of P. intermedia in the progression of periodontal disease.

Animals↗

Procarbazine genotoxicity in the MutaMouse; strong clastogenicity and organ-specific induction of lacZ mutations.

Procarbazine, a drug used for cancer chemotherapy, is carcinogenic in rodent bioassays. We analyzed the mutagenicity of procarbazine in various organs and the clastogenicity of the drug in hematopoietic cells of the lacZ transgenic MutaMouse. This was part of the second collaborative study of the Mammalian Mutagenesis Study Group of the Japanese Environmental Mutagen Society on the transgenic mouse mutation assay. At 50 mg kg(-1), procarbazine induced micronuclei in hematopoietic cells, but it did not increase the lacZ mutant frequency (MF) in bone marrow. It was also negative in liver, testis, spleen, kidney, and lung. Five daily administrations of 150 mg kg(-1) yielded highly positive responses in the drug's target organs for carcinogenesis (lung, bone marrow, and spleen). Lower positive responses were detected in kidney, which is a minor target organ. Liver showed only a slight increase in lacZ MF and brain showed no increase. The testis MF more than doubled which suggest that procarbazine is mutagenic to germ cells. Thus, we demonstrated that procarbazine has a strong clastogenic effect in hematopoietic cells and is mutagenic in a variety organs after high dose treatment. The induced MF was especially high in procarbazine's target organs for carcinogenesis, which supports the relevance of the transgenic mouse mutation assay for the assessment of potential genotoxins in vivo.

Animals↗

Chemiluminescence detection of heme proteins separated by capillary isoelectric focusing.

Chemiluminescence detection was combined with capillary isoelectric focusing to perform protein analysis with high sensitivity. Luminol-H2O2 chemiluminescence was utilized, and heme proteins such as cytochrome c, myoglobin and peroxidase were analyzed. The proteins were focused by use of Pharmalyte 3-10 as ampholytes. Hydroxypropylmethyl-cellulose was added to the sample solution in order to easily reduce protein interactions with the capillary wall as well as the electroendoosmotic flow. The focused proteins were transported by salt mobilization to chemiluminescence detection cell equipped with an optical fiber. The present method showed significantly high sensitivity and wide dynamic range; the detection limit for cytochrome c was 6 x 10(-9) M and the linear dynamic range was greater than two-orders of magnitude (up to 2 x 10(-6) M).

Calibration↗

Over-expression of GAPDH induces apoptosis in COS-7 cells transfected with cloned GAPDH cDNAs.

The cDNAs for glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) were cloned from cerebellar neurons undergoing age-induced apoptosis and/or healthy cells. COS-7 cells were transfected with the isolated GAPDH cDNAs using to the Lipofectamine method. Assessment of cell death in this paradigm was performed by monitoring the co-transfected luciferase activities and the characterization of cell death was examined by the DNA fragmentation assay and Hoechst dye nuclear staining. These observations show that over-expression of GAPDH occurring from both cDNAs robustly induces apoptotic death in the transfected COS-7 cell cultures. Confocal-immunocytochemical studies using this GAPDH-specific monoclonal antibody revealed that nuclear translocation of overexpressed GAPDH is a primary apoptotic event. Our results directly demonstrate that over-expressed GAPDH functions as a 'killing protein' in apoptosis.

Animals↗

Superiority of platelet integrin GPIIb-IIIa receptor antagonist over aspirin in preventing cyclic flow reductions in the guinea pig middle cerebral artery.

We established a photothrombotic occlusion model in the guinea pig middle cerebral artery. In this model, the middle cerebral artery was recanalized within 10 to 20 min after thrombotic occlusion, with subsequent cyclic flow reductions. Cyclic flow reductions in the middle cerebral artery are expected to manage cerebral infarction by modulating arterial patency. Therefore, we evaluated the effect of several antiplatelet agents on the frequency of cyclic flow reductions and subsequent cerebral infarction using this model. A platelet integrin GPIIb-IIIa receptor antagonist, ME3277 (sodium hydrogen [4-[(4,5,6,7-tetrahydrothieno[3,2c]pyridin-2-yl) carbonylamino] acetyl-o-phenylene] dioxydiacetate, 0.3, 1 and 3 mg/kg i.v.) dose-dependently inhibited the ex vivo platelet aggregation induced by ADP (5 microM), collagen (0.8 and 20 microg/ml) and arachidonic acid (100 microM). While the same doses of ME3277 reduced the frequency of the cyclic flow reductions and increased the total patency time of the middle cerebral artery, time to thrombotic occlusion was prolonged only at the highest dose, 3 mg/kg. ME3277 (0.3-3 mg/kg) significantly reduced the infarct volume and improved the neurological deficit at 24 h. In contrast, aspirin (30 mg/kg) did not affect these variables in spite of complete inhibition of platelet aggregation induced by arachidonic acid and collagen (0.8 microg/ml). A thromboxane A2 synthetase inhibitor, sodium ozagrel, significantly increased the total patency time and reduced the infarct volume at 30 mg/kg. Inhibition of prostaglandin I2 generation could explain the effectiveness of sodium ozagrel but not aspirin in this model. These results suggest that platelet integrin GPIIb-IIIa receptor antagonists are more beneficial than aspirin for the treatment of cerebral thrombosis.

Amides↗

Temporal bone histopathologic findings in a case of interstitial deletion of the long arm of chromosome 2 [del(2) (q31q33)].

The temporal bones of a 24-day-old female neonate with an interstitial deletion of the long arm of chromosome 2 [del(2)(q31q33)] were studied histopathologically, focusing mainly on the inner ear. This is, to our knowledge, the first report of a temporal bone study in a case of this chromosomal aberration. The abnormalities included a shortened cochlea with underdeveloped modiolus in both ears. Total absence of the spiral ganglion cells and the cochlear nerve bundle, accompanied by obliteration of the fundus of the internal auditory meatus by a bony plate, and dislocation of some geniculate ganglion cells to the internal auditory meatus were also observed in the right ear. The absence of the spiral ganglion cells is considered to be the result of some complication in the early fetal life, such as dysgenesis or early degeneration of the neuronal cells. The organ of Corti in the right ear was well-developed and preserved in the middle turn, suggesting that the differentiation of the cochlear sensory epithelium in humans is not dependent upon the innervation, at least on the gross level.

Abnormalities, Multiple↗

Mechanistic studies of catechins as antioxidants against radical oxidation.

The antioxidative mechanisms of catechins were studied by investigating products generated at the first stages by 2, 2'-azobis(2-aminopropane)hydrochloride (AAPH)-induced radical oxidation, without any isolation, using LC/MS, spectrophotometry, and PM3 semiempirical molecular orbital (MO) calculations. Catechins were quite effective in scavenging peroxyl radicals in a liposomal system and in an aqueous system except for (-)-epigallocatechin (EGC). EGC was the least effective among four catechins tested. From the results of LC/MS and spectroscopic studies, (-)-epicatechin (EC) would be gently converted to an anthocyanin-like compound. According to the mechanisms, the compound produced from EC by radical oxidation can also function as an antioxidant. As a result, EC has a longer inhibition period (tinh = 9360 s). On the other hand, EGC decreased shortly after oxidation (tinh = 3420 s) and was transformed to a quinone-like compound. The addition of superoxide dismutase (SOD) reduced the chemiluminescence from EGC during oxidation. Active oxygen including superoxide anion radicals (O-2) may be produced in the case of EGC, but not in the case of EC. However, EGC has a more rapid scavenging effect on peroxyl radicals (kinh/kp = 232) than EC (kinh/kp = 41). The calculated C-H bond dissociation enthalpies (BDEs) for catechins at the C-2 position were unexpectedly low (65 kcal/mol) compared to O-H BDEs at phenolic sites (70 kcal/mol), suggesting that hydrogen at the C-2 position may be abstracted by free radicals. The authors propose the tentative antioxidative mechanisms of catechins depending on the experimental results and theoretical calculations.

Amidines↗

Phase II trial of 5-fluorouracil and low-dose cisplatin in patients with squamous cell carcinoma of the esophagus.

A phase II study was conducted to determine the clinical efficacy and toxicity of 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) in patients with squamous cell carcinoma of the esophagus. Chemotherapy consisted of 5-FU at a dose of 330 mg/m2 per day, given as a 24-h infusion on days 1-7, and CDDP at a dose of 6 mg/m2 per day, given as a 2-h infusion on days 1-5. Either two or four cycles of chemotherapy were administered to 20 patients with stage III advanced esophageal carcinoma. All 20 patients were then assessed for response and toxicity. An objective response was demonstrated by 11 of the 20 patients, with one complete response (CR) and ten partial responses (PR), bringing the response rate to 55%, with a 95% confidence interval of 27% to 83%. Surgical resection of the tumor was performed in all 20 patients. One patient was found to have a grade 3 histological CR. The median survival of all the patients was 20.5 months, with a range of 4.5 to 48.0 months. Neutropenia and thrombocytopenia developed in five (25%) and two (10%) patients, respectively, and the nonhematologic toxicities were insignificant. The findings of this phase II study indicate that preoperative treatment using 5-FU and low-dose CDDP chemotherapy for patients with advanced esophageal carcinoma appears to achieve a high response rate after short-term administration without affecting the quality of sophisticated lymph node dissection.

Aged↗

Surgery for descending thoracic aortic anastomotic aneurysms with a temporary external bypass method.

The surgical treatment of descending thoracic aortic anastomotic aneurysms is technically challenging. The purpose of this study was to evaluate the use of a temporary external bypass method as an intraoperative measure in the surgical treatment of anastomotic aneurysms of the descending thoracic aorta. An analysis of five consecutive patients who had undergone surgery for a collective seven descending thoracic aortic anastomotic aneurysms in our university hospital over a period of 14 years was conducted. A temporary bypass technique was used as an intraoperative measure in all the operations, four of which were performed with a right axillary to left external iliac artery bypass, while other sites were used in the remaining three. Systemic heparinization was able to be avoided in six operations and was markedly reduced in the remaining one. Although the major postoperative complication was coagulated hemothorax after six procedures, all patients recovered well and are still alive after a mean follow-up period of 8.2+/-1.5 (SEM) years. The results of this analysis led us to conclude that our temporary bypass method for treating descending thoracic aortic anastomotic aneurysm prevented the risks of anticoagulant administration for circulatory support, which contributed to the success of the operation. This method can be used as adjunct treatment for anastomotic aneurysms in the descending thoracic aorta.

Adult↗

Mediastinal esophageal cyst causing unilateral hyperlucent lung.

Unilateral emphysema secondary to bronchial obstruction by a foregut-derived mediastinal cyst is rare. Here we describe an infant with a unilateral hyperlucent lung due to compression on the left main bronchus by an esophageal cyst, visualized by chest computed tomography and magnetic resonance imaging. A chest roentgenogram and a perfusion scan presented the normalized left lung after resection of the cyst.

Esophageal Cyst↗

Does neoadjuvant chemotherapy for carcinoma in the thoracic esophagus increase postoperative morbidity?

OBJECTIVES: The aims of this study were to examine whether neoadjuvant chemotherapy for a carcinoma in the thoracic esophagus increased the incidence of postoperative complications, and which clinicopathological factors may affect postoperative complications after esophagectomy. SUBJECTS AND METHODS: One hundred and forty-four patients who underwent neoadjuvant chemotherapy followed by esophagectomy for a carcinoma in the thoracic esophagus were reviewed in a retrospective study. Ninety-six patients received neoadjuvant chemotherapy and 48 did not. The postoperative complications were grouped either general complications (Complications A) or surgery-related complications (Complications B). Complications A consisted of pulmonary, cardiac, hepatic, renal, and neurological complications, and catheter sepsis. Complications B consisted of a gastrointestinal tract leak, gastrointestinal tract necrosis, an intrathoracic or intraabdominal abscess, hemorrhage, ileus, and vocal cord palsy. In these two categories of complications, 17 factors obtained from subjects were compared between patients with complications and those without by univariate and multivariate analyses. RESULTS: The patient characteristics did not differ between patients who received neoadjuvant chemotherapy and those without. The preoperative serum albumin level was higher in patients without complication than in those with complication in both two categories of complications (Complications A: p = 0.001, Complications B: p = 0.05). The proportion of patients who received neoadjuvant chemotherapy did not differ between patients with complication and those without complication in either category of complications. Multivariate analysis showed that preoperative Onodera's Prognostic Nutritional Index was the only factor reducing the incidence of complications A (p = 0.02, Odds ratio: 0.63). CONCLUSION: Neoadjuvant chemotherapy was well tolerated and was not associated with any increased morbidity or mortality after esophagectomy for a carcinoma in the thoracic esophagus.

Chemotherapy, Adjuvant↗

Developmental expression of GLUT2 in the rat retina.

We previously demonstrated that GLUT2, a facilitated-diffusion glucose transporter isoform known to play critical roles in the regulation of systemic blood glucose level, is present at the apical ends of Müller cells in the rat retina. As a means of elucidating the ontogeny and possible role(s) of GLUT2 in the developing retina, this study examined its expression at various stages of retinal development by immunofluorescence staining using GLUT2-specific antibody. Evidence of GLUT2 expression first appeared at embryonic day 14 (E14) as linear staining along the boundary between the inner and outer layers of the optic cup, with this staining pattern being present throughout subsequent embryonic and neonatal stages. After the development of photoreceptor cell inner and outer segments (i.e., photoreceptor layer), GLUT2 immunoreactivity was localized along the boundary between the outer nuclear layer and photoreceptor layer. Localization of GLUT2 expression and the timing of its appearance, which coincided with the formation of choriocapillaries, together suggest that GLUT2 is involved in the anterior transport of glucose supplied by choroidal circulation from the early stages of retinal development.

Animals↗

Milrinone, a phosphodiesterase inhibitor, suppresses intimal thickening after photochemically induced endothelial injury in the mouse femoral artery.

The effect of milrinone, a phosphodiesterase (PDE) inhibitor, on intimal thickening after endothelial denudation was investigated. Intimal thickening was induced in the femoral arteries of mice by a photochemical reaction between rose bengal and transluminal green light which caused endothelial injury followed by platelet adhesion, aggregation, and formation of an occlusive thrombus in the irradiated segment of the mouse femoral artery. In this model, intimal thickening occurred following spontaneous thrombolysis. The intima/media ratio at 21 days after irradiation was 0.556+/-0.104 in the untreated group. Oral administration of milrinone (0.3-3.0 mg/kg) for 3-21 days suppressed intimal thickening by up to 56% in a dose- and time-dependent manner. In an in vivo experiment using bromodeoxyuridine incorporation, milrinone suppressed cell proliferation at 1.0 mg/kg p.o. On the other hand, the minimum doses of milrinone for suppression of ex vivo platelet aggregation induced by collagen (0.8 microg/ml) or ADP (0.5 microM) were 3.0 and 10.0 mg/kg, respectively. These results indicate that milrinone may not suppress intimal thickening by inhibiting platelet function but by preventing vascular smooth muscle cell (VSMC) proliferation, probably through a mechanism mediated via 3', 5'-adenosine cyclic monophosphate (cAMP).

Animals↗