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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 307 records · Page 17Linked to original sources
PubMed1999

Overexpressed lipoprotein lipase protects against atherosclerosis in apolipoprotein E knockout mice.

Lipoprotein lipase (LPL) is known to play a crucial role in lipoprotein metabolism by hydrolyzing triglycerides; however its role in atherogenesis has yet to be determined. We have previously shown that low density lipoprotein receptor knockout mice overexpressing LPL are resistant to diet-induced atherosclerosis due to the suppression of remnant lipoproteins. Plasma lipoproteins and atherosclerosis of apolipoprotein (apo) E knockout mice which overexpress the human LPL transgene (LPL/APOEKO) were compared with those of control apoE knockout mice (APOEKO). On a normal chow diet, LPL/APOEKO mice showed marked suppression of the plasma triglyceride levels compared with APOEKO mice (54 vs. 182 mg/dl), but no significant changes in plasma cholesterol and apoB levels. Non-high density lipoproteins (HDL) from LPL/APOEKO mice had lower triglyceride content, a smaller size, and a more positive charge compared with those from APOEKO mice. Cholesterol, apoA-I, and apoA-IV were increased in HDL. Although both groups developed hypercholesterolemia to a comparable degree in response to an atherogenic diet, the LPL/APOEKO mice developed 2-fold smaller fatty streak lesions in the aortic sinus compared to the APOEKO mice. In conclusion, overproduction of LPL is protective against atherosclerosis even in the absence of apoE.

Animals↗
PubMed1999

PEG-rHuMGDF ameliorates thrombocytopenia in carboplatin-treated rats without inducing myelofibrosis.

We examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on carboplatin-induced thrombocytopenia in rats. The focus was on whether myelofibrosis is associated with the PEG-rHuMGDF treatment in this chemotherapy model. After a single injection of carboplatin, rats received subcutaneous PEG-rHuMGDF at pharmacologic doses (1,3, or 30 micrograms/kg) or a vehicle daily for 7 days. PEG-rHuMGDF at more than 3 micrograms/kg ameliorated the thrombocytopenia at day 10. Histologically, no myelofibrosis was detected in the rats treated with PEG-rHuMGDF or vehicle. Subsequently, PEG-rHuMGDF at a suprapharmacologic dose (100 micrograms/kg) was subcutaneously administered to normal and to carboplatin-treated rats daily for 7 days. Histological analysis revealed that the treatment with PEG-rHuMGDF induced myelofibrosis in the normal rats but not in the carboplatin-treated rats. Additionally, the transforming growth factor-beta 1 (TGF-beta 1) levels in the extracellular fluid and the whole extract of the bone marrow were increased to a much lesser degree in the carboplatin-treated rats compared to the normal rats. These findings suggest that PEG-rHuMGDF is effective for carboplatin-induced thrombocytopenia. Proper control of platelet counts and TGF-beta 1 levels is essential so that myelofibrosis is not induced in clinical use.

Animals↗
PubMed1999

Proton MR spectroscopy of Sjögren-Larsson's syndrome.

We performed single-voxel proton MR spectroscopy (1H-MRS) in two children with Sjögren-Larsson's syndrome (SLS). Both patients showed two abnormal spectral peaks at 1.3 ppm and 0.9 ppm that were obtained with short echo times. These two abnormal spectral peaks were seen in high-intensity areas on T2-weighted images and also in basal ganglia of normal intensities. 1H-MRS may be useful for establishing the diagnosis and investigating the natural history of SLS, and for evaluating the efficacy of therapeutic approaches to SLS.

Aldehyde Oxidoreductases↗
PubMed1999

[A long-survival case of gastric cancer with multiple liver metastasis: usefulness of intraoperative multimodality therapy and post-operative intra-arterial chemotherapy for liver lesions].

A 62-year-old man was found to have advanced cancer of the gastric cardia with multiple liver metastasis. Total gastrectomy was performed, and 11 hepatic lesions were simultaneously treated by intraoperative multimodality therapy. The therapy included hepatic resections for seven easily-resectable lesions, microwave coagulation therapy for two lesions, and ethanol injection therapy for two. Post-operative intra-arterial infusion of 1,000 mg of 5-FU was performed weekly or every two weeks through the hepatic artery using a reservoir. No recurrence was found during the follow-up period of 35 months. When local control is obtained during surgery in patients with gastric cancer with multiple liver metastasis, intraoperative multimodality therapy and post-operative intra-arterial chemotherapy should be performed for liver lesions.

Adenocarcinoma↗
PubMed1999

[A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of docetaxel].

Docetaxel is an excellent agent with a high antitumor effect for the treatment of advanced/recurrent breast cancer. A 55-year-old female with metastatic liver tumors from breast cancer showed a remarkable response to intra-arterial administration of docetaxel (20 mg/week, or 40 mg/2 weeks). Since CT and MRI imaging revealed multiple metastases in the liver, intra-arterial chemotherapy was selected. No critical side effect was found during this chemotherapy. A CT scan 3 months after chemotherapy showed a partial response. We conclude that this intra-arterial chemotherapy using docetaxel will be safe and useful for liver metastases from breast cancer.

Adenocarcinoma, Scirrhous↗
PubMed1998

Intratumoral cytogenetic heterogeneity detected by comparative genomic hybridization and laser scanning cytometry in human gliomas.

Although it is well-known that cancers show intratumoral phenotypic heterogeneity, genotypic studies have been scarce. Using comparative genomic hybridization and laser scanning cytometric analyses, we investigated intratumoral cytogenetic heterogeneity in 21 surgically removed gliomas including 11 glioblastomas (GBMs), 8 anaplastic astrocytomas (AAs) and 2 low-grade astrocytomas. Comparative genomic hybridization analysis revealed gain or amplification of 7p in 63%, gain of 7q in 73%, loss of 9p in 53%, loss of 10p in 47%, loss of 10q in 47%, loss of 13q in 53%, and loss of 22q in 37% of high-grade astrocytomas. Because these aberrations were region-independent within the same tumor, they did not contribute to intratumoral cytogenetic heterogeneity. Such heterogeneity was due to cytogenetic changes other than the above region-independent aberrations. Intratumoral cytogenetic heterogeneity was detected in 8 of 11 GBMs, 4 of 8 AAs, and none of the 2 low-grade astrocytomas. These observations suggest that cytogenetic changes at chromosomes 7, 9p, 10, 13, and 22 are primary events in high-grade astrocytomas and that subsequent cytogenetic changes involving increases in copy number provide intratumoral heterogeneity. DNA aneuploidy was detected by laser scanning cytometry in 5 of 11 GBMs and 1 of 8 AAs. All tumors with DNA aneuploidy exhibited intratumoral cytogenetic heterogeneity, and there was a significant correlation between DNA aneuploidy and intratumoral cytogenetic heterogeneity. These results support the notion that cytogenetic heterogeneity results from genetic instability within a tumor.

Adult↗
PubMed1998

Mechanical stretch induces hypertrophic responses in cardiac myocytes of angiotensin II type 1a receptor knockout mice.

Many lines of evidence have suggested that angiotensin II (AngII) plays an important role in the development of cardiac hypertrophy through AngII type 1 receptor (AT1). To determine whether AngII is indispensable for the development of mechanical stress-induced cardiac hypertrophy, we examined the activity of mitogen-activated protein kinase (MAPK) family and the expression of the c-fos gene as hypertrophic responses after stretching cultured cardiac myocytes of AT1a knockout (KO) mice. When cardiac myocytes were stretched by 20% for 10 min, extracellular signal-regulated protein kinases (ERKs) were strongly activated in KO cardiomyocytes as well as wild type (WT) myocytes. Both basal and stimulated levels of ERKs were higher in cardiomyocytes of KO mice than in those of WT mice. Activation of another member of the MAPK family, p38(MAPK), and expression of the c-fos gene were also induced by stretching cardiac myocytes of both types of mice. An AT1 antagonist attenuated stretch-induced activation of ERKs in WT cardiomyocytes but not in KO cardiomyocytes. Down-regulation of protein kinase C inhibited stretch-induced ERK activation in WT cardiomyocytes, whereas a broad spectrum tyrosine kinase inhibitor (genistein) and selective inhibitors of epidermal growth factor receptor (tyrphostin, AG1478, and B42) suppressed stretch-induced activation of ERKs in KO cardiac myocytes. Epidermal growth factor receptor was phosphorylated at tyrosine residues by stretching cardiac myocytes of KO mice. These results suggest that mechanical stretch could evoke hypertrophic responses in cardiac myocytes that lack the AT1 signaling pathway possibly through tyrosine kinase activation.

Animals↗
PubMed1998

In situ morphometric analysis of the coronary arterial growth in perinatal rats.

The perinatal changes in the diameters of left and right coronary arteries in rats were studied using the rapid whole body freezing technique. The main portion of the left coronary artery and left anterior descending and circumflex branches rapidly increased in diameter after birth as well as ascending aorta. The ratios of the diameters of the left coronary artery and anterior descending branch to the diameter of ascending aorta increased significantly after 4 days of age. In contrast, there were no significant changes in the diameter of the right coronary artery from the fetus to the 8-day-old pups and the ratio of the right coronary artery to the ascending aorta significantly decreased after birth. We report here that the left coronary artery in rats increases in diameter more rapidly than the right coronary artery in the early newborn period.

Animals↗
PubMed1998

Cholesterol lowering in low density lipoprotein receptor knockout mice overexpressing apolipoprotein E.

Apo E is a key molecule in the lipoprotein metabolism; thus, genetic manipulation of apo E may prove useful in the treatment of hypercholesterolemia. To test the feasibility of this idea, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpress the rat apo E transgene (ETg+/+:LDLRKO), and compared their plasma lipoprotein profiles with those of nonexpressing LDLR knockout mice (ETg-/-:LDLRKO). On a normal chow diet, the mean plasma cholesterol level of ETg+/+:LDLRKO mice was significantly lower than that of ETg-/-:LDLRKO mice (189 versus 240 mg/dl, P < 0. 01). The LDL fraction was selectively reduced in the ETg+/+:LDLRKO mice. Despite the challenge with an atherogenic diet, cholesterol lowering was persistently observed and fatty streak lesions in the aortic sinus were significantly suppressed in the mice overexpressing apo E. These results imply that stimulation of hepatic production of apo E may be used as a promising adjunctive therapy for homozygous familial hypercholesterolemia.

Animals↗
PubMed1998

Separation of lac dye components by high-speed counter-current chromatography.

High-speed counter-current chromatography has been successfully applied to the separation of the lac dye components. A 25-mg quantity of the sample was separated using a two-phase solvent system composed of tert.-butyl methyl ether-n-butanol-acetonitrile-water (2:2:1:5). The fractions were analyzed by high-performance liquid chromatography and electrospray tandem mass spectrometry. The separation yielded 2.6 mg of 97.2% pure laccaic acid C, 9.5 mg of 98.1% pure laccaic acid A, 3.6 mg of 98.2% pure laccaic acid B, and 0.5 mg of a 95.0% pure anthraquinonedicarboxylic acid with a molecular mass of 360.

Azo Compounds↗
PubMed1998

Abnormal left ventricular diastolic filling patterns in small-for-gestational-age infants.

Doppler transmitral flow velocity patterns in assessing left ventricular diastolic function in small-for-gestational-age infants have been poorly understood. The purpose of this study is to examine Doppler filling patterns in small-for-gestational-age infants (n = 13) and to compare them with those in age-matched appropriate-for-gestational-age infants (n = 29). We measured peak flow velocities of early diastole (peak E wave) and atrial contraction (peak A wave), ratio of peak E wave to peak A wave (peak E/A wave), velocity time integrals of E wave (VTIE wave) and A wave (VTIA wave), ratio of VTIE wave to VTIA wave (VTIE/A wave), first third filling fraction, peak filling rate normalized to stroke volume, and deceleration time. Mean gestational age and heart rate did not show a significant difference between the appropriate- and the small-for-gestational-age infants. The mean birth weight in the small-for-gestational-age infants was significantly lower than that in the appropriate-for-gestational-age infants (802+/-220 vs. 1184+/-260 g, P<0.01). In the small-for-gestational-age infants, the peak E wave, peak A wave, peak E/A wave,VTIE wave, first third filling fraction, and peak filling rate normalized to stroke volume were significantly lower than those in the age-matched appropriate-for-gestational-age infants (21.9+/-6.7 vs. 32.2+/-6.9 cm/s, 26.5+/-6.2 vs. 34.5+/-6.2 cm/s, 0.82+/-0.15 vs. 0.93+/-0.14, 1.88+/-0.45 vs. 2.39+/-0.51 cm, 0.36+/-0.04 vs. 0.41+/-0.04, 5.86+/-0.75 vs. 7.11+/-0.63/s, P<0.05, respectively). In the small and appropriate for gestational age infants, peak E wave, VTIE wave, and peak E/A increased significantly with increasing body weight. In the small-for-gestational-age infants, the slopes of regression lines between body weights and peak E wave and VTIE wave were significantly lower than those in the appropriate for gestational age infants, suggesting a significant reduction in E wave even when considering a difference in their body weight. This study suggests that the significant decreases in the early diastolic filling in the small-for-gestational-age infants may be related to the reduced left ventricular diastolic function.

Blood Flow Velocity↗
PubMed1998

Separation of antibiotics by counter-current chromatography.

This paper reviews recent applications of counter-current chromatography (CCC) to the separation of antibiotics. It also covers the recent development of CCC instruments and the optimization of the two-phase solvent system. The CCC technique offers a high resolving power when the proper solvent system is carefully selected and becomes a powerful tool to separate various components from antibiotics complexes.

Anti-Bacterial Agents↗
PubMed1998

Mass spectrometric analysis of tetracycline antibiotics in foods.

We will review recent developments in mass spectrometric analysis of tetracycline antibiotics (TCs) in foods. The mass spectrometric techniques discussed are as follows: the collision-activated decomposition mass-analysed ion kinetic energy spectrometry (CAD MIKES), thin-layer chromatography (TLC)- fast atom bombardment (FAB) mass spectrometry (MS), particle beam (PB) liquid chromatography (LC)-MS, LC-fit FAB MS, thermospray (TSP) LC-MS, atmospheric chemical ionization (APCI) LC-MS and tandem electrospray (ESI) LC-MS. Their advantages and limitations are described in the confirmation of TCs in foods: CAD MIKES can confirm TCs with high sensitivity; however, its practical application is questionable because of uncommon instrumentation. TSP has a problem in reproducibility of the mass spectrum. Although TLC-FAB-MS can be applied to any kind of samples, it cannot be used for the quantitative analysis. LC-frit FAB-MS is a useful technique for the confirmation of TCs in honey, but it cannot be applied to animal tissues because of a lack of sensitivity. PB negative chemical ionization, APCI, and ESI-MS-MS can reliably confirm TCs in foods with good reproducibility.

Anti-Bacterial Agents↗
PubMed1998

Lethality of high linear energy transfer cosmic radiation to Escherichia coli DNA repair-deficient mutants during the 'SL-J/FMPT' space experiment.

We investigated the lethal and mutagenic effects of high linear energy transfer cosmic radiation on 11 strains of Escherichia coli, including DNA repair-deficient mutants, using the Radiation Monitoring Container and Dosimeter in the space shuttle 'Endeavour' as part of the 'SL-J/FMPT' space experiment, the 'Fuwatto '92' project. After the return to earth of the shuttle, we evaluated survival and mutations of samples in space and matched controls. The surviving fractions were determined by means of colony count on broth agar plates, and the mutation frequencies were estimated by appearance of arg' revertants on minimal agar plates. The average of the total equivalent dose rate during this space flight was 0.202 mSv/day as measured by the plastic radiation detectors and the thermoluminescent dosimeters in the Radiation Monitoring Container and Dosimeter. The combined action of DNA polymerase and 3'-->5' exonuclease activities was found to make the greatest contribution to the repair of cosmic radiation-induced DNA damage, 5'-->3' exonuclease and recombination repair enzyme activities made a moderate contribution, whereas UV endonuclease activity was not involved in this DNA repair process.

Colony Count, Microbial↗