Biomedical subjects

K Morimoto

Publications and source records attributed to K Morimoto.

At least 127 records · Page 7Linked to original sources

PubMed1999

Preparation of a complex of dexamethasone palmitate-low density lipoprotein and its effect on foam cell formation of murine peritoneal macrophages.

In the early progression of atherosclerosis, LDL migrates in the subendothelial space of the artery and plays an important role in foam cell formations of macrophages. LDL may serve as a carrier of site-specific delivery of drugs to atherosclerotic lesions. In this exploratory study, dexamethasone palmitate (DP) was incorporated in LDL, and an inhibitory effect of this complex on foam cell formations was examined. LDL was isolated from human plasma, and the DP-LDL complex was prepared by incubation in the presence of Celite 545. No degradation nor modification of LDL was observed. The DP/LDL molar ratio of the complex was 35-50:1. Foam cell formations of murine macrophages were induced by incubation with oxidized LDL. When macrophages were pretreated with the DP-LDL complex, accumulation of cholesterol ester in the macrophages induced by oxidized LDL, i.e., an index of foam cell formation, was decreased. These findings indicated that the DP-LDL complex showed similar characteristics to LDL, and the DP-LDL complex inhibited foam cell formations of macrophages in vitro. This study provides the basis for further study of the DP-LDL complex as a drug-carrier complex for treatment of atherosclerosis.

Animals↗

PubMed1999

Disposition of radioactivity after injection of liver-targeted proteins labeled with 111In or 125I. Effect of labeling on distribution and excretion of radioactivity in rats.

The effect of radiolabeling liver-specific proteins on the in vivo disposition of radioactivity was investigated. The suitability of 111In and 125I as radiolabels for protein disposition studies in vivo was examined. Galactosylated and cationized bovine serum albumin were labeled with either 125I by the chloramine-T method or 111In, using 1-(4-isothiocyanatobenzyl)ethylenediaminetetraacetic acid (SCN-BZ-EDTA) or diethylenetriaminepentaacetic acid (DTPA) as bifunctional chelating agents (BCAs) and administered intravenously to rats. 125I radioactivity disappeared rapidly from the liver with subsequent excretion in the urine and bile, mainly in the TCA soluble fraction. 111In-associated radioactivity, on the other hand, remained in the hepatic tissue in considerably higher amounts during the experiment and was excreted in the bile and urine to a lower extent when compared with 125I. When the effect of BCA on excretion of 111In radioactivity was compared, no significant differences were observed in the urinary clearances. However, biliary excretion was significantly higher for 111In-SCN-BZ-EDTA-bound radioactivity. In conclusion, when compared with 125I, 111In labeling seems to more accurately characterize the in vivo distribution of liver-targeted proteins after their iv administration in rats and allows a more accurate pharmacokinetic evaluation to be performed.

Albumins↗

PubMed1999

Genetic dissection of the complex pathological manifestations of collagen disease in MRL/lpr mice.

An MRL strain of mice bearing a Fas-deletion mutant gene, lpr, MRL/MpJ-lpr/lpr (MRL/lpr) develops collagen disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjögren's syndrome, respectively. Development of such lesions seems dependent on host genetic background since the congenic C3H/HeJ-lpr/lpr (C3H/lpr) mice rarely develop them. To identify the gene loci affecting each lesion, a genetic dissection of these complex pathological manifestations was carried out. First, histopathological features in MRL/lpr, C3H/lpr, (MRL/lpr x C3H/lpr) F1 intercross, and MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice were analyzed. Genomic DNA of the backcross mice were subjected to association studies by Chi-squared analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. As a result, gene loci recessively associated with each lesion were mapped on different chromosomal positions. We concluded that each of these lesions in MRL/lpr mice is under the control of a different set of genes, suggesting that the complex pathological manifestations of collagen disease result from polygenic inheritance.

Animals↗

PubMed1999

Validation study of the in vitro micronucleus test in a Chinese hamster lung cell line (CHL/IU).

We conducted a collaborative validation study, under the auspices of the Japanese Ministry of Labour, on the in vitro micronucleus test to see if it could be used as an alternative to the in vitro chromosome aberration test for evaluation of chemical safety. We used the Chinese hamster lung cell line (CHL/IU), which is the most widely used system for the latter test in Japan, and evaluated 66 chemicals, including clastogens and polyploidy inducers. The cytochalasin B cytokinesis blocking method, which is commonly used in human lymphocyte culture, was applied to the established cell line, but did not improve the detection of chemically-induced micronuclei in continuously growing cells. The highest micronucleus frequencies were obtained at 48 or 72 h continuous treatments. In short treatments (6 h), a 42 h recovery time yielded the best responses. Concordance between the results of the micronucleus test and the chromosomal aberration test was satisfactorily high (88.7%), and we concluded that the in vitro micronucleus test could be used in place of the chromosomal aberration test as a simple and rapid method for detecting clastogens and aneugens in vitro. We also propose a protocol for the test.

Animals↗

PubMed1999

Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients.

A case-control study was conducted to explore the possible etiologic role of alcohol and aldehyde dehydrogenase 2 (ALDH2) gene among Japanese colorectal cancer patients. Information on their drinking, smoking and dietary habits was collected from 265 colon and 164 rectum cancer patients, and 794 non-cancer patients as a control group. Genotypes of the ALDH2 gene at codon 487, glutamic acid (ALDH2*1) as a wild-type or lysine (ALDH2*2) as a mutated type with reduced enzyme activity, were analyzed by polymerase chain reaction in 160 colon and 110 rectum cancer patients and 121 control persons. Univariate analysis with the chi 2 statistical test showed that heavy alcohol drinking (P < 0.01), frequent meat intake (P < 0.001), and irregular (P < 0.01), hasty (P < 0.01) and excessive (P < 0.001) eating habits were associated with the incidence of both colon and rectum cancers, whereas heavier smoking (P < 0.05) and infrequent fish (P < 0.03) and fruit (P < 0.01) intake were solely associated with incidence of rectum cancer. Infrequent green vegetable intake was not correlated with the incidence of colorectal cancer. Multivariate unconditional logistic regression analysis confirmed the association of alcohol consumption (P < 0.01) and meat intake (P < 0.05). Homozygous and heterozygous carriers of ALDH2*2 allele tended to be found in colon (trend P = 0.04) but not in rectum cancer patients compared to controls. Risk elevation for colon cancer due to alcohol consumption was pronounced among the heterozygotes and it was statistically significant especially for distal colon cancer (trend P = 0.02). We conclude that alcohol consumption is a risk factor for colorectal cancer and the risk can be enhanced in ALDH2 heterozygotes.

Adult↗

PubMed1999

[Outbreak case caused by different colicin type of Shigella sonnei in a day nursery in Tokyo (1998)].

From October through December, 1998, person to person infection caused by Shigella sonnei had occurred in the day nursery in Hachioji-city Tokyo, and a total of 41 patients including 3 suspected cases and 3 carriers had been confirmed. Although one case was imported case which is one-year-old kindergarten child, the remaining was domestic case. Of patients, 33 cases (80.5%) were a three-year-old kindergarten children and their families, accounting for 20 and 13 cases, respectively. From the data of symptom onset of patients, epidemic could distinguish to the former part and the later part. The recur or reinfection, and re-detection case was observed in the later part. Clinical symptom of the patients was diarrhea (100%), fever (80%) and abdominal cramps (70%), and LVFX for adult or FOM for child was used for the therapy. In the colicin typing test and the antibiotic susceptibility test for 9 reagents, almost isolates in the former part were type 0 and susceptible, and MBC for FOM ranged from 6.25 to 100 micrograms/ml, whereas those in the later part was type 2 and resistant for the TC, and showed highly MBC for FOM with 50 or 100 micrograms/ml. However, both isolates showed same patterns in plasmid profiles and DNA fingerprints by RAPD analysis. On the other hand, the strain from imported case was also colicin 0, but it was different as regards resistant for ABPC and ST and two genetic analysis.

Adult↗

PubMed1999

[Report of questionnaire survey for methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae in the Kinki District].

In the Kinki District (Hyogo area, Osaka City area, Osaka Outskirts area, Nara area and Wakayama area), a questionnaire survey of 30 institutions was conducted for methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). Median number of their bed was 500 ranging 0 to 1076, 3239 (56%) of the 5815 strains of S. aureus were methicillin-resistant. Although no different prevalence was found among the areas, they were predominantly isolated from sputum of inpatients more than from outpatients, 336 (44%) of the 763 strains of S. pneumoniae were penicillin-resistant. The prevalence rate was the highest in the outpatients in Osaka outskirts. Almost all strains of MRSA were sensitive to vancomycin (VCM) and sulfamethoxazole trimethoprim (ST). Resistant strains were observed in 2% against arbekacin, 6% against amikacin, 44% against minocycline (MINO), and in 54% against gentamicin (GM). Almost all strains of PRSP were sensitive to VCM and ST. Resistant strains were observed in 75% against erythromycin, 50% against MINO, and 75% against GM. This survey identified the trend of hospital infection for MRSA and community infection for PRSP, and sensitive drugs for the treatment.

Cross Infection↗

PubMed1999

Pathogenicity of different rabies virus variants inversely correlates with apoptosis and rabies virus glycoprotein expression in infected primary neuron cultures.

The mouse-adapted rabies virus strain CVS-24 has stable variants, CVS-B2c and CVS-N2c, which differ greatly in their pathogenicity for normal adult mice and in their ability to infect nonneuronal cells. The glycoprotein (G protein), which has previously been implicated in rabies virus pathogenicity, shows substantial structural differences between these variants. Although prior studies have identified antigenic site III of the G protein as the major pathogenicity determinant, CVS-B2c and CVS-N2c do not vary at this site. The possibility that pathogenicity is inversely related to G protein expression levels is suggested by the finding that CVS-B2c, the less pathogenic variant, expresses at least fourfold-higher levels of G protein than CVS-N2c in infected neurons. Although there is some difference between CVS-B2c- and CVS-N2c-infected neurons in G protein mRNA expression levels, the differential expression of G protein appears to be largely determined by posttranslational mechanisms that affect G protein stability. Pulse-chase experiments indicated that the G protein of CVS-B2c is degraded more slowly than that of CVS-N2c. The accumulation of G protein correlated with the induction of programmed cell death in CVS-B2c-infected neurons. The extent of apoptosis was considerably lower in CVS-N2c-infected neurons, where G protein expression was minimal. While nucleoprotein (N protein) expression levels were similar in neurons infected with either variant, the transport of N protein into neuronal processes was strongly inhibited in CVS-B2c-infected cells. Thus, downregulation of G protein expression in neuronal cells evidently contributes to rabies virus pathogenesis by preventing apoptosis and the apparently associated failure of the axonal transport of N protein.

Animals↗

PubMed1999

Prediction of coronary artery lesions in unstable angina by iodine 123 beta-methyl iodophenyl pentadecanoic acid (BMIPP), a fatty acid analogue, single photon emission computed tomography at rest.

Iodine 123 beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP), a beta-methyl-branched fatty acid analogue, has been proven by experimental studies to reveal abnormalities in fatty-acid-related metabolism. This study was undertaken to validate the accuracy and limitations of 123I-BMIPP imaging at rest in detecting myocardial metabolic abnormalities and predicting coronary lesions in unstable angina (UA). One hundred UA patients without prior myocardial infarction were studied. 123I-BMIPP and thallium 201 chloride (201TlCl) imaging with single photon emission computed tomography (SPECT) and coronary and left ventricular cineangiography (LVC) were performed 1 week after the last episode of angina. There was reduced uptake of 123I-BMIPP imaging in 70 patients, reduced uptake of 201TlCl in 41, and abnormal LVC contraction in 49 patients. There were significant increases in severity scores of 123I-BMIPP imaging along with increases in the number of stenosed coronary arteries and the severity of stenosis in individual coronary arteries. There was a significant reduction in 123I-BMIPP severity scores 1 month after percutaneous transluminal coronary angioplasty (p < 0.01) and a significant correlation between the severity scores of 123I-BMIPP and LVC (r=0. 579, p<0.001). Overall rates of sensitivity and specificity in detecting significant coronary stenosis by 123I-BMIPP imaging were 74% and 86%, respectively, whereas rates of sensitivity and specificity in detecting significant coronary stenosis by 201TlCl were 31% and 91%, respectively. 123I-BMIPP sensitivity increases to 86% if only advanced coronary stenosis of >90% is included. In conclusion, 123I-BMIPP myocardial imaging is an effective method of predicting coronary artery lesions of UA patients without provocative test.

Adult↗

PubMed1999

VXFD in the cytoplasmic domain of macrophage scavenger receptors mediates their efficient internalization and cell-surface expression.

We determined the endocytosis motif sequence of macrophage scavenger receptors by measuring the internalization of the ligand-bound cell-surface scavenger receptors at the early stage. Mutation experiments have indicated that the 28 amino acids at the N-terminal cytoplasmic domain are important for both efficient internalization and cell-surface expression of the receptor. The substitution of alanine for Val21, Phe23 or Asp24 reduced both the efficiency of internalization and the cell-surface expression of the receptors; in addition, that for Val28 reduced only the internalization efficiency and that for Lys22 reduced only the cell-surface expression of the receptors. Western blot experiments showed that the total levels of expression of the mutant receptors in the cells were approximately the same and all the mutants were identified in the membrane fraction. This suggests that the Val21, Lys22, Phe23 and Asp24 mutants are localized in membranes other than the cell-surface membrane by missorting. All our results indicate that VXFD is the motif sequence essential for not only the coated-pit-mediated endocytosis of macrophage scavenger receptors but also for the trafficking of the receptors to the cell surface.

Animals↗

PubMed1999

Structural characterization of recombinant human erythropoietins by fluorophore-assisted carbohydrate electrophoresis.

Routine analysis of the carbohydrate moieties of a glycoprotein is critical for ensuring the consistent quality of biopharmaceutical products. Fluorophore-assisted carbohydrate electrophoresis (FACE) is a recently introduced method for the separation, by polyacrylamide gel electrophoresis, of oligosaccharides labeled with 8-amino-naphthalene-1,3,6-trisulphonic acid (ANTS). In this study, we have evaluated the applicability of the FACE method to analysis of the carbohydrate moieties of three different recombinant human erythropoietins (rHuEPOs), two Chinese hamster ovary (CHO) cell-derived rHuEPOs, and one baby hamster kidney (BHK) cell-derived rHuEPO. The N-linked oligosaccharides released from the rHuEPOs were labeled with ANTS. Enzymic sequence analysis of the N-linked oligosaccharides was performed by the FACE method. The results showed that the FACE method was useful for the analysis of sialo-, asialo-, and agalacto-oligosaccharides in the same gel. Its usefulness for rapidly and reliably revealing the oligosaccharide profiles of given glycoproteins, and its reproducibility were also confirmed in this study. In conclusion, the method can be used for evaluating the quality consistency of recombinant glycoprotein products in terms of the carbohydrate moiety.

Animals↗

PubMed1999

Tracheal barrier and the permeability of hydrophilic drugs and dipeptides.

The permeability of model hydrophilic compounds with different molecular weights and model dipeptides were examined to characterize the tracheal epithelial barrier in in vitro experiments using excised rabbit trachea. 6-Carboxyfluorescein (6-CF; 376 Da) and fluorescein isothiocyanate (FITC)-dextrans (FDs) with varying molecular weights (4 to 70 kDa) were used as model hydrophilic and macromolecular compounds, and glycyl-D-phenylalanine (Gly-D-Phe) and glycyl-L-phenylalanine (Gly-L-Phe) were used as model dipeptides in this experiment. The apparent permeability coefficients (Papp) of 6-CF and FDs with Mw 376 Da to 70 kDa ranged from 2.35x10(-7) to 4.05x10(-10)cm/s and exhibited a good inverse correlation with their molecular weights. The tracheal permeability of 6-CF, FD-4 (4 kDa) and FD-10 (10 kDa) were increased over three fold by 10 mM glycocholate, which is an absorption enhancer. The Papp of Gly-D-Phe was 1.03x10(-6)cm/s and there was no metabolism during tracheal permeation. Gly-L-Phe was immediately degraded in the mucosal fluid and its intact form was not detected in serosal fluid during the 150 min experimental period. These results suggest that absorption of some peptide drugs via the respiratory tract may contribute to their systemic delivery following pulmonary administration by intratracheal insufflation and instillation.

Animals↗

PubMed1999

Thrombosed dissection of the ascending aorta complicating extravasation.

This report presents 2 patients with thrombosed dissection of the ascending aorta complicating extravasation. The first case was an 85-year-old male admitted with shock due to cardiac tamponade. Plain computed tomography (CT) demonstrated a dilated ascending aorta without clear evidence of aortic dissection. The second case was a 77-year-old female presenting with shock, in whom an enhanced CT scan demonstrated a dilated ascending aorta and periaortic effusion. However, dissection of the distal ascending aorta was not identified in either case before emergency surgery. In case 1, soon after the bloody pericardial effusion was decompressed during the operation, bleeding from the ascending aorta occurred. A small intimal tear was found in the distal ascending aorta, and in each case the pseudolumen was filled with fresh thrombus. The ascending aorta was replaced. Each patient had an uneventful postoperative recovery. Based on this experience, it is suggested that patients with thrombosed ascending aortic dissection complicating extravasation should undergo early graft replacement.

Aged↗

PubMed1999

Reduced urination rate while drinking beer with an unpleasant taste and off-flavor.

A lowered subjective evaluation of the taste and flavor of beer due to staleness or to the addition of an unpleasant taste and flavor was found to be closely correlated with the urination rate. Beer in the same lot was compared immediately after shipment from the brewery and after leaving at room temperature for 1 month or 5 months. Each beer sample was given to volunteers at the rate of 3 ml/kg/15 min for 2 hours, and the urine volume was measured every 30 minutes. The urination rate was highest from the volunteers who drank fresh beer and lowest from those who drank 5-month-old beer. The subjective evaluation of both the taste and drinkability of 5-month-old beer was significantly lower than that of fresh beer. Beer samples with various unpleasant taste and flavor substances added lowered the urination rate. The results suggest that the perception of an unpleasant taste and off-flavor would lower the urination rate.

Adult↗

PubMed1999

Therapy-related megakaryoblastic leukemia with pituitary involvement following treatment for non-Hodgkin's lymphoma.

A case of a 66-year-old Japanese man developed therapy-related megakaryoblastic leukemia with pituitary involvement after chemotherapy for non-Hodgkin's lymphoma. Alkylating agents had been administered for the treatment of non-Hodgkin's lymphoma and 6 years later, megakaryoblastic leukemia with myelofibrosis and myelodysplasia developed. The blast cells expressed CD41, and immature antigens also. These findings were compatible with therapy-related megakaryoblastic leukemia. An autopsy revealed blast-cell infiltration into multiple organs including the posterior pituitary lobe. Therapy-related megakaryoblastic leukemia is very rare, and pituitary involvement may be associated with immaturity of blast cells.

Antigens, CD↗

PubMed1999

Prevention of occupational allergy caused by exposure to acid anhydrides.

This paper focuses on the prevention of IgE-mediated symptoms of the eyes and airways caused by exposure to acid anhydrides in the workplace. Acid anhydrides are widely used in the production of alkyd resins and as curing agents for epoxy resins. Heavy exposure to acid anhydrides causes severe irritation. However, reports of direct irritation of mucous membranes or skin are rare in recent years, since a package of multiple engineering controls has been introduced to reduce exposure. On the other hand, acid anhydrides are well-known industrial inhalant sensitizers and can cause occupational allergy even at very low exposure intensities. Therefore, safe use in industry demands both control of the level of exposure causing allergic diseases in the workshop and programmes for prevention of occupational allergy.

Anhydrides↗

PubMed1999

Determination of methyltetrahydrophthalic anhydride in air using gas chromatography with electron-capture detection.

Methyltetrahydrophthalic anhydride (MTHPA) stimulates the production of specific IgE antibodies which can cause occupational allergy even at extremely low levels of exposure (15-22 micrograms/m3). Safe use in industry demands control of the levels of exposure causing allergic diseases. Thus, the air monitoring of MTHPA is very important, and sensitive methods are required to measure low air concentrations or short-time peak exposures. This paper outlines the use of silica-gel tubes for sampling airborne MTHPA vapour, followed by analysis using gas chromatography with electron-capture detection. No breakthrough was observed at 113, 217, 673 and 830 micrograms/m3 (sampling volume 30, 60, 60 and 20 l, respectively; relative humidity 40-55%). Concentrations > 1.0 microgram/m3 could be quantified at 20-min sampling with a sampling rate of 1 l/min. The present method can also be applied to measurements of exposure to hexahydrophthalic and methylhexahydrophthalic anhydride. The risk of MTHPA exposure in two condenser plants was also assessed by determining MTHPA levels in air of the workplace. In conclusion, our method was found to be reliable and sensitive, and can be applied to the evaluation of MTHPA exposure.

Air Pollution, Indoor↗

PubMed1999

[A case of chronic myelogenous leukemia presenting multiple extramedullary tumors localized in cranial dura].

A 64-year-old woman had been given a diagnosis of Ph-positive chronic myelogenous leukemia (Ph+ CML) in October 1992 and accordingly treated with interferon-alpha busulfan, and hydroxyurea. She was admitted to our hospital with a one-day history of consciousness disturbance on May 30, 1993. Two weeks before admission, she had received chemotherapy consisting of vincristine and predonisolone because of progressive thrombocytopenia, basophilia, and leukocytosis accompanied by a heightened degree of cell immaturity in peripheral blood and bone marrow. Cranial computerized tomography on admission disclosed tumoral masses in the left frontal lobe and the right temporal lobe. Moreover, lumbar puncture ezinkns disclosed blastoid cells in cerebrospinal fluid. Based on these laboratory findings, the diagnosis was blastic crisis CML, 46XX t(9; 22; 17) (q34; q11; q23), cytogenetic aberration and extramedulary brain disease Although the patient underwent the same combined chemotherapy again, her unconsciousness did not resolve. She died of cerebellar herniation on the 7th hospital day. Post mortem examination revealed three extramedullary tumors localized in cranial dura. This was a rare case of CML presenting multiple extramedullary tumors localized in cranial dura.

Blast Crisis↗