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Biomedical subjects

M Kato

Publications and source records attributed to M Kato.

At least 973 records · Page 54Linked to original sources
PubMed1996

Oral biological activities of spontaneous nitric oxide releasers are accounted for by their nitric oxide-releasing rates and oral absorption manners.

We examined whether p.o. biological activities of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), a spontaneous nitric oxide (NO) releaser, and the derivatives, i.e., (+/-)-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexenyl]-3 - pyridinecarboxamide (FR144420) and (+/-)-N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-6-methyl-5- nitro-3-heptenyl]-3-pyridinecarboxamide (FR146801), could be accounted for by their NO-releasing rates and p.o. absorption manners. These compounds spontaneously released NO with the rates in the rank order of FK409 > FR144420 > FR146801. Total contribution of these drugs as NO donors in vivo was almost the same from the determination of urinary nitrite/nitrate (NOx) levels after p.o. administration of the compounds at 10 mg/kg to rats. Plasma NOx level after p.o. administration of FK409 at 10 mg/kg to rats reached maximal level at 120 min, and decreased gradually. On the other hand, plasma NOx levels time-dependently increased during 360 min after p.o. administration of FR144420 and FR146801 at the same dose. FK409 and FR144420 showed hypotensive effects immediately after p.o. administration at 10 mg/kg to rats, and the maximum response of FR144420 was less and the duration of the effect was longer than those of FK409, respectively. On the other hand, FR146801, which is most stable in solution, did not show any significant hypotensive effect during 240 min after p.o. administration at the same dose. In conclusion, the response and the duration of biological activity after p.o. administration of three spontaneous NO releasers can be closely accounted for by their NO-releasing rates and p.o. absorption manners.

Absorption↗
PubMed1996

[Diagnosis and targeting therapy of colorectal cancer using antibody].

Application of monoclonal antibody for diagnosis and therapy of colorectal cancer was reviewed. The history and present status of radioimmunoimaging of cancer were presented. Immuno-guided surgery using radiolabeled antibody and hand-aided detector during surgery is a promising approach for complete excision of cancerous region. Also, a new antibody labeling method using a micro-magnet instead of radioisotopes may lead to a new era in immunodiagnosis of cancer. Finally, immunotargeting chemotherapy using antibody-anticancer drug conjugates was reviewed. A new type of immunoconjugate composed of human/mouse chimeric antibody and Neocarzinostatin seems to be one of the most promising drug formulas for immunotargeting chemotherapy.

Antibiotics, Antineoplastic↗
PubMed1996

Amount of pollen has an effect on the systemic and local levels of soluble ICAM-1 in patients with seasonal allergic rhinitis.

We investigated whether the amount of antigen has an effect on the systemic and local levels of soluble ICAM-1 (sICAM-1) in patients with pollinosis, and assessed its biologic significance. The levels of subjective symptoms and sICAM-1 in sera and nasal epithelial lining fluids (ELF) from 14 subjects with pollinosis (allergic group) and eight healthy subjects (control group) were measured from pre- to postseason in 1993 (total pollen count: 10,854/cm2) and 1994 (total pollen count: 415/cm2), and the results were compared with each other among the four groups. The levels of subjective symptoms and sICAM-1 in ELF from the allergic group significantly increased during the season in both 1993 and 1994. However, there was a significant difference (P < 0.01) between the levels of those in 1993 and those in 1994 during the season. The levels of sICAM-1 in sera from the allergic group were significantly upregulated during the seasons and postseasons only in 1993, and there was a significant difference (P < 0.05) between the levels in 1993 and those in 1994 during the postseason. We conclude that amount of pollen has an influence on the local and systemic levels of sICAM-1, as well as the scores of subjective symptoms, in patients with seasonal allergic rhinitis.

Adult↗
PubMed1996

LD50 value, phototoxicity and convulsion induction test of the new quinolone antibacterial agent (S)-10-[(S)-(8-amino-6-azaspiro[3,4]octan-6-yl)]-9-fluoro-2, 3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxyl ic acid hemihydrate in laboratory animals.

(S)-10-[(S)-(8-Amino-6-azaspiro[3,4]octan-6-yl)]-9-fluoro-2, 3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxyli c acid hemihydrate (CAS 151390-79-3, DV-7751a) a new quinolone antibacterial agent, was examined for LD50 value, phototoxicity and convulsion inducing potential in laboratory animals. A single oral administration of DV-7751a induced soft stool in rats at 1000 and 2000 mg/ kg and in monkeys at 250 mg/kg and vomiting in monkeys at 500 mg/kg or more. A single intravenous administration caused a decrease in locomotor activity, respiratory depression, convulsion, pulmonary edema and death in rats and mice. The LD50 values with oral administration were more than 2000 mg/ kg for rats and mice and more than 250 mg/kg for monkeys, and those with intravenous administration were 164.3 mg/kg for rats of both sexes at an injection rate of 2 ml/min, 118.8 mg/kg for male rats and 104 to 125 mg/kg for female rats at 0.5 ml/min, and 184.7 mg/kg for male mice and 187.4 mg/kg for female mice. DV-7751a showed very weak phototoxicity in mice after single oral administration of 600 mg/kg, followed by UVA irradiation, but no convulsion after oral administration of 200 or 1000 mg/kg in combination with 4-biphenylacetic acid at 400 mg/kg.

Administration, Oral↗
PubMed1996

[Pulmonary lymphangiomyomatosis with tuberous sclerosis and endolymphatic stromal myosis of the uterus].

Pulmonary lymphangiomyomatosis is a rare disorder that affects only women of reproductive age. The lung shows numerous cystic changes and striking proliferation of smooth muscle around the airways, blood vessels, and lymphatic channels. We encountered a patient with pulmonary lymphangiomyomatosis who had repeated pneumothorax and bloody sputum over 10 years. The patient also had other lesions, including intracranial calcification, renal angiomyolipoma and endolymphatic stromal myosis of the uterus. The first two findings are known as tuberous sclerosis, and lymphangiomyomatosis is considered to be a form fruste of tuberous sclerosis. However, we know of no previous reports of uterine lesions in this disease. Lymphangiomyomatosis may be a systemic disorder of smooth muscle.

Adult↗
PubMed1996

One-month oral toxicity study of the new quinolone antibacterial agent (S)-10-[(S)-(8-amino-6-azaspiro[3,4]octan-6-yl)-9-fluoro-2,3-dihydro-3- methyl-7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid hemihydrate in rats and cynomolgus monkeys.

One-month oral toxicity of (S)-10-[(S)-(8-amino-6-azaspiro[3,4] octan-6-yl)]-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate (CAS 151390-79-3, DV-7751a) a new quinolone antibacterial agent was investigated in Sprague-Dawley rats at doses of 12.5, 50, 200 and 800 mg/kg/d and in cynomolgus monkeys at 10, 30 and 100 mg/kg/d. Rats receiving 200 mg/ kg showed abnormal urine crystals, enhanced deposition of lipid in hepatocytes and exacerbation of osteochondrotic lesions in the femoral condyle. In addition, dosing at 800 mg/kg induced decrease in body weight gain and increased levels of serum alkaline phosphatase (ALP), cholinesterase, leucine aminopeptidase and total cholesterol. Monkeys receiving 100 mg/kg showed abnormal urine crystals and increases in serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and ALP levels. The non-toxic doses of DV-7751a in rats and monkeys were 50 and 30 mg/kg, respectively, under the present experimental conditions.

Animals↗
PubMed1996

[Locoregional therapy for liver metastases of colorectal cancer].

The role of biological response modifiers (BRM) in locoregional therapy for liver metastases of colorectal cancer was studied clinically and experimentally. Seven patients with numerous metastases to both lobes of liver were given intraarterial administration of BRM in combination with anticancer drugs. A partial response was observed in 1 patient. The response rate was 14.3%. Alternatively, intraarterial administration of both OK-432 and IL-2 into the rabbit with liver metastases of VX-2 tumors could bring about the infiltration of cytotoxic T lymphocytes around the tumors, followed by a significant decrease of the metastatic nodules. In addition, the same anti-tumor effect was observed when PSK was administered intraperitoneally into the BALB/c mouse with liver metastases of colon 26 tumors. Moreover, the therapeutic effect of water in oil type emulsion encapsulating both OK-432 and IL-2 was greater than that of the solution of BRM in BALB/c mouse with liver metastases of colon 26 tumors. These results indicated that BRM could be one of the promising agents in locoregional therapy against liver metastases of colorectal cancer.

Adult↗
PubMed1996

Body mass index (BMI) is a reliable index to estimate obesity as a risk factor for deteriorating health.

The objective of this study was to find out what index is appropriate to evaluate obesity, by measuring body fat using bioelectrical impedance analysis (BIA). Subjects in this study were 74 women, aged 44 to 73, living in Tokushima prefecture. The means +/- standard deviation (SD) of Broca index, Body mass index (BMI) and body fat were 103 +/- 14.3%, 23.0 +/- 2.8 kg/m2 and 28.1 +/- 5.5%, respectively. In addition, their clinical data such as blood pressure, glutamate-pyruvate transaminase activity (GPT), triglycerides (TG) and fasting blood sugar (FBS) were within normal ranges. When compared with correlation between obesity indices (Broca index or BMI) and height, there was a negative correlation between Broca index and height (= -0.447). Furthermore, the number of obese subjects estimated by Broca index was less than that of obese subjects estimated by BMI. Although both Broca index and BMI showed higher correlations with body fat estimated by BIA, BMI (r = 0.927) showed a higher correlation compared to that of Broca index (r = 0.875). These results suggest that BMI is a reliable index to evaluate the body fat.

Adipose Tissue↗
PubMed1996

Lung cancer-reacting human recombinant antibody AE6F4: potential usefulness in the sputum cytodiagnosis.

Human monoclonal antibody (hMAb) AE6F4 has been shown to be potentially useful for immunocytological detection of lung cancer cells in sputum. By recombinant DNA technology, IgM type hMAb AE6F4 was switched to lgG. The IgG mimic recombinant AE6F4 antibody expression plasmid was assembled using the antibody heavy chain gene, which ligated the gene encoding VH and CH1(mu) domains of hMAb AE6F4 heavy chain to the gene encoding CH2(gamma 1) and CH3(gamma 1) domains of human IgG heavy chain, and the antibody light chain gene of hMAb AE6F4. The recombinant antibody expressed by baby hamster kidney (BHK)-21 cells showed molecular size equivalence to IgG, and consisted of human mu-gamma hybrid heavy and kappa light chains. The immunological specificity of the recombinant antibody was the same as that of hMAb AE6F4 by immunoblotting analysis to the 14-3-3 protein, the putative antigen of hMAb AE6F4, and by immunohistochemical and immunocytological analyses using tissue sections and sputa of lung cancer patients. The transfected BHK-21 cells produced the recombinant antibody persistently and the productivity was greater than 20 times that by human-human hybridoma producing hMAb AE6F4.

14-3-3 Proteins↗
PubMed1996

Zopiclone pharmacodynamics: by monitoring event-related potentials and psychometric scores.

To investigate the pharmacological effects of zopiclone in the central nervous system, we monitored event-related potentials (ERPs, N100 and P300), the reaction time and the scores for subjective mental and emotional state (by using the Polarity Profile Questionnaire, PPQ) on 10 healthy right-handed male volunteers between 21 and 32 years old. Subjects were randomly allocated to receive a single oral administration of zopiclone 7.5 mg or placebo at the first-session, and the drug was crossed over at the second session 1 week later. ERPs, the reaction time and the psychometric scores were monitored at pre-drug, and 1, 3 and 5 hours after drug administration. In the zopiclone group, the reaction time was prolonged significantly at 1 hour after drug administration, the amplitudes of the ERPs significantly decreased at 1 and 3 hours after, and the PPQ scores showed significant changes. Maximum effects on the psychometric scores appeared later than those on ERPs and reaction time. Zopiclone decreased the arousal level and sensory sensitivity, and induced sedation through changes in subjective mental and emotional states.

Administration, Oral↗
PubMed1996

[A case of familial juvenile dystonia-parkinsonism: 18F-6-fluorodopa and 18F-fluoro-2-deoxyglucose PET study].

A 27-year-old Japanese woman was admitted to Kyoto University Hospital because of gait disturbance since age 25. Her elder sister had been suffering from childhood-onset dystonia-parkinsonism with diurnal fluctuation which initially responded well to levodopa therapy, but later larger dose of levodopa was needed because of severe treatment-related fluctuation of the clinical symptoms. Physical examination revealed left foot dystonia, mild parkinsonism with kinesie paradoxale and dyskinesia of lower limbs. Symptoms were relieved by sleep and worsened by walking. Laboratory data including serum ceruloplasmin, serum and urinary amino acid analysis, and hexosaminidase and beta-glucosidase activity in leukocytes were all normal. Homovanillic acid (HVA) in cerebrospinal fluid was normal (68 ng/ml) at 8 pm but markedly decreased (7 ng/ml) at 4 pm. Cranial MRI was normal. 18F-6-fluorodopa PET demonstrated decreased dopa uptake in the bilateral striatum, especially in the putamen. 18F-fluoro-2-deoxyglucose PET showed decreased regional glucose metabolism in the bilateral putamen. Levodopa therapy rendered equivocal effects while trihexyphenydil was effective. This case indicated that some cases of dopa-unresponsive dystonia with parkinsonism might be a clinical variant of juvenile parkinsonism. 18F-6-fluorodopa PET is useful in evaluating juvenile dystonia-parkinsonism, though it may not predict levodopa effectiveness. 18F-fluoro-2-deoxyglucose PET study will be helpful in predicting the effect of levodopa therapy, because decreased regional glucose metabolism in the putamen probably indicates poor response to levodopa. Further study including dopaminergic receptor imaging study is needed to clarify the physiological mechanism of co-existing dystonia and parkinsonism in patients with juvenile parkinsonism and related disorders.

Adult↗
PubMed1996

Significance of serum free prostate specific antigen in the screening of prostate cancer.

PURPOSE: The significance of serum free prostate specific antigen (PSA) in the screening of prostate cancer was examined. MATERIALS AND METHODS: A prospective clinical trial was conducted on 701 male volunteers 50 years old or older. Serum free PSA was determined and biopsies were performed if PSA was greater than 4 ng./ml. or if digital rectal examination was suspicious for cancer. RESULTS: Of the men 187 (27%) had a PSA of greater than 4 ng./ml. (11%) and/or a suspicious digital rectal examination (19%). Of 116 biopsies performed in the 701 men cancer was detected in 13 (1.9%). PSA detected more tumors (12 of 13, 92%) than digital rectal examination (9, 69%). Receiver operating characteristic analysis showed that the optimal free PSA-to-PSA ratio (free PSA ratio) was 12%. The positive predictive value for cancer according to PSA with free PSA ratio (50%, 10 cancers in 20 biopsies) was significantly greater (p = 0.0473) than that according to PSA alone (24%, 12 cancers in 50 biopsies), which indicated that 30 of 50 biopsies were avoided with only 2 cancers missed when PSA and free PSA were used for biopsy indication. CONCLUSIONS: Free PSA determination might eliminate unnecessary biopsies in men with a PSA of more than 4 ng./ml. with minimal missed cancers.

Aged↗
PubMed1996

[Initial experience with partial left ventriculectomy as a treatment for end-stage heart failure].

PURPOSE: To evaluate the efficacy of left ventriculectomy, on a short term basis, as a treatment for patients with end-stage heart failure. METHODS: From February to June 1995, 7 patients with end-stage heart failure underwent partial left ventriculectomy. Before the surgical procedure, 7 (100%) patients were in functional class IV. Three (42%) patients needed inotropic support for hemodynamic stability. The mean daily dose of furosemide was l48.67 +/- 128.27 mg, of captopril 87.50 +/- 95.20 mg and of digoxin 0.23 +/- 0.04. Mean left ventricular diastolic dimension determined by 2-D echocardiography was 78.29 +/- 12.63 mm, mean left ventricular ejection fraction, determined by radionuclide ventriculography, was 0.15 +/- 0.05 whereas mean transpulmonary gradient and pulmonary vascular resistance in Wood units, determined by right heart catheterization, were 16.80 +/- 8.80 and 6.57 +/- 3.22, respectively. RESULTS: Sixty days after the surgery, the mean functional class was 1.71 +/- 0.48 (p = 0.009), the mean left ventricular diastolic dimension 64.67 +/- 11.41 mm (p = 0.02) and the mean left ventricular ejection fraction 0.22 +/- 0.04 (p = 0.02). CONCLUSION: The left ventriculectomy is a promising treatment for patients with end-stage heart failure.

Cardiac Surgical Procedures↗
PubMed1996

[Retrograde aortic dissection during cardiopulmonary bypass a case report successfully treated by contralateral femoral cannulation].

Retrograde aortic dissection is the most critical complication associated with femoral perfusion. It may be related to the trauma of femoral cannulation per se or to the jet of retrograde perfusion. We report the successful repair of a retrograde aortic dissection by composite graft replacement of the dissected ascending aorta using contralateral femoral cannulation. A 66-year-old man presented with aortic regurgitation due to annuloaortic ectasia. At the operation, the right common femoral artery was cannulated, and cardiopulmonary bypass was initiated. Within a few minutes after beginning the bypass, we recognized a retrograde dissection showing a tense bluish bulge in the ascending aorta. Bleeding was detected from the dissected aortic root beside the right coronary ostium. The bypass was interrupted, and contralateral femoral cannulation was performed immediately to re-establish the bypass. Composite graft replacement of the aortic root and ascending aorta was successfully performed under hypothermic circulatory arrest using additional retrograde cerebral perfusion. Pathological findings of the aortic wall revealed cystic medionecrosis. When a retrograde aortic dissection occurs, it is essential to establish antegrade flow. If it is impossible to cannulate at the ascending aorta for any reason, a contralateral femoral cannulation can be used successfully to re-establish the cardiopulmonary bypass because of the easy access.

Aged↗
PubMed1996

[8;21 translocation acute myelocytic leukemia developing in the second trimester of pregnancy with successful delivery].

A 28 year-old woman in the 26th week of pregnancy was admitted to our hospital on February 6, 1993, because of anemia and thrombocytopenia. On admission, her hemoglobin was 8.2 g/dl, platelet count 6.3 x 10(4)/microliter, and WBC 6,300/microliter with 43% blasts. The bone marrow examination showed hyperplastic bone marrow with 38.8% blasts. She was diagnosed as having 8;21 translocation acute myelocytic leukemia (M2). In the 30th week of pregnancy, she gave birth to a 1449 g male infant by induction delivery. After DCMP therapy, complete remission was obtained. She has been in complete remission for 32 months and her child is growing healthy after overcoming an underweight condition due to premature birth, respiratory distress syndrome, circulation insufficiency and hyperbilirubinemia. This case suggests that in the event of second trimester pregnant patients with acute leukemia, we should wait for the proper time at which successful delivery can be expected, and then intensified remission induction chemotherapy should be carried out after the delivery.

Adult↗
PubMed1996

Loss of expression of transforming growth factor beta type I and type II receptors correlates with tumor grade in human prostate cancer tissues.

Transforming growth factor beta1 (TGF-beta1) is a potential regulator of prostate cancer cell growth that signals through a heteromeric complex composed of type I and type II receptors. In the present study, an attempt was made to establish a correlation between expression of TGF-beta receptors and tumor grade in archival human prostate cancer tissues. To this end, immunohistochemical studies for TGF-beta receptors were carried out on 32 cases of human prostate cancer and 8 samples of benign human prostate. In both benign and malignant human prostate tissues, immunoreactivity for both type I and type II receptors was detected predominantly in epithelial cells. In addition, there was an inverse correlation between the loss of expression of TGF-beta1 type I and type II receptors and the tumor grade. Of the 32 prostate cancer cases screened, staining was completely absent in four samples for type II receptor (P < 0.05) and eight samples for type I receptor (P < 0.025). In contrast, all eight samples of benign prostate tissues investigated in this study showed strong staining for both type I and type II receptors. These results, taken together, indicate that human prostate cancer cells frequently have loss of expression of TGF-beta type I and/or type II receptors. Furthermore, these observations provide a potential mechanism for prostate cancer cells to escape the growth-inhibitory effect of TGF-beta.

Activin Receptors, Type I↗