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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 721 records · Page 40Linked to original sources
PubMed1995

A 6-kb upstream region of the human transthyretin gene can direct developmental, tissue-specific, and quantitatively normal expression in transgenic mouse.

To ascertain whether a 6-kb upstream region of the human transthyretin (TTR) gene contains the cis-element(s) required for proper specificity and level of expression, transgenic mice carrying the human mutant TTR gene containing either 6-kb (6.0-hMet30) or 0.6-kb (0.6-hMet30) of the upstream region were produced and studied. The 6.0-hMet30 gene was expressed in the yolk sac, liver, and choroid plexus, where the mouse endogenous TTR gene is also expressed. In contrast, expression of the 0.6-hMet30 gene was restricted to the yolk sac and liver. The expression levels of the 6.0-hMet30 gene in the liver and serum were similar to those of the mouse TTR gene, and about 10-fold those of the 0.6-hMet30 gene. Before birth, the developmental profiles of the expression of both transgenes in each tissue were similar to those of the mouse TTR gene. However, the expression levels of the 6.0-hMet30 gene in the liver and serum increased after birth to reach adult levels at an age of 4 weeks, while expression of the 0.6-hMet30 gene remained at a low level after birth. These results suggest that the 6-kb upstream sequence contains the cis-elements required for developmental, tissue-specific, and quantitatively normal expression.

Animals↗
PubMed1995

Expression of P450 17 alpha-hydroxylase and P450aromatase genes in isolated granulosa, theca interna, and theca externa layers of chicken ovarian follicles during follicular growth.

Concentrations of estradiol (E), testosterone (T), and progesterone (P) and levels of the 1.9-kb and 4.0-kb mRNA encoding P450 17 alpha-hydroxylase (P450 17 alpha) and P450aromatase (P450arom), respectively, were measured in the isolated granulosa, theca interna, and theca externa of the largest preovulatory (F1-F4) follicles of the chicken 20 h and 3 h before expected ovulation of F1. In the granulosa layer, E and T concentrations remained low throughout this period of follicular growth, whereas P concentrations were high 3 h before ovulation in F2 and F1 follicles. E levels were highest in the theca interna and externa of the smallest (F4) follicle, decreasing progressively with follicular growth. T content of theca interna and granulosa was greater in less mature F4-F2 follicles than in the most mature (F1) follicle, whereas theca externa contained little T. P was quantifiable in significant amounts only in granulosa tissue, peaking in F2 and F1 follicles at 3 h before ovulation, at which time plasma levels of steroids also rose significantly. P450 17 alpha was expressed mainly in theca interna, whereas the P450arom mRNA levels found in theca externa reflected the pattern of E in this compartment. Expression of these two genes was very low in granulosa tissue, remaining unchanged during follicular growth. These results indicate that E and T synthesis in the chicken ovary is regulated, at least in part, at mRNA levels of P450 17 alpha and P450arom in the theca interna and theca externa layers during follicular growth.

Animals↗
PubMed1995

Pathologic support for limited hepatectomy in the treatment of liver metastases from colorectal cancer.

OBJECTIVE: The authors determined an appropriate surgical treatment for liver metastases from colorectal cancers. Clinicopathologic features of metastatic lesions of colorectal cancers were studied. SUMMARY BACKGROUND DATA: Major hepatic resection is the usual procedure for treatment of hepatic metastases from colorectal cancers. METHODS: Forty consecutive patients who underwent hepatic resections were prospectively studied, for a total of 89 metastatic liver tumors. RESULTS: Metastatic tumor often extended along Glisson's capsule, including invasion to the portal vein (9 cases), the hepatic vein (3 cases), the bile duct (16 cases), and the nerve (6 cases). The main tumor had small satellite nodules in only one patient, and there were no microscopic deposits in the parenchyma, even within 10 mm from the metastatic tumors. Fibrous pseudocapsule formation was observed in 28 patients. DISCUSSION: The rarity of intrahepatic metastasis from metastatic tumor supports nonanatomic limited hepatic resection as the procedure of choice for metastatic colorectal cancer in the liver. The spread via Glisson's capsule should be taken into consideration for complete tumor clearance.

Adenocarcinoma↗
PubMed1995

Chloroflexus aggregans sp. nov., a filamentous phototrophic bacterium which forms dense cell aggregates by active gliding movement.

Two strains of thermophilic photosynthetic bacteria, designated MD-66T (T = type strain) and YI-9, were isolated from bacterial mats in two separate hot springs in Japan. These new isolates were phenotypically similar to Chloroflexus aurantiacus in some respects. They were thermophilic filamentous photosynthetic bacteria that grew well at 55 degrees C either anaerobically as photoheterotrophs or aerobically as chemoheterotrophs. They exhibited gliding motility, produced bacteriochlorophylls a and c, contained chlorosomes, and required thiamine and folic acid as growth factors. However, isolates MD-66T and YI-9 had the ability to rapidly form mat-like dense aggregates of filaments, an ability which has not been observed in any C. aurantiacus strain. Carbon source utilization tests revealed that unlike C. aurantiacus, the new isolates did not utilize acetate, citrate, ethanol, or glycylglycine. An analysis of the carotenoid components revealed that isolates MD-66T and YI-9 contained mainly gamma-carotene and OH-gamma-carotene glucoside fatty acid esters. These isolates also contained only trace amounts of beta-carotene, which is a major carotenoid component (28.4% of the total carotenoids) in C. aurantiacus. The results of DNA hybridization studies suggested that the new strains were genetically distinct from C. aurantiacus (levels of similarity, 9 to 18%), and 16S rRNA sequence comparisons showed that strain MD-66T was related to C. aurantiacus at a similarity level of 92.8%. On the basis of our data, we propose that a new Chloroflexus species should be created for our new isolates; the name of this new species is Chloroflexus aggregans, and the type strain is strain MD-66 (= DSM 9485).

Bacteria↗
PubMed1995

Inflammatory cytokines and rat vascular tone.

1. Experiments were performed to examine the effect of inflammatory cytokines, interleukin-2 (IL-2), IL-6 and IL-8, on the contractility of rat aorta. 2. Pretreatment of the endothelium-denuded aortic ring with IL-6 for 3 h caused a significant inhibition of its contraction (58.9 +/- 7.8%, n = 9, P < 0.01) when induced by 10(-6) mol/L phenylephrine. 3. On the other hand, IL-2 and IL-8 failed to show significant effects on the contractility of the aorta. 4. This inhibitory effect of IL-6 on phenylephrine-induced contraction showed dose-dependency, and completely disappeared in the presence of 10(-5) mol/L indomethacin. 5. In cultured rat vascular smooth muscle cells (VSMC), the release of 6-keto-prostaglandin F1alpha into the extracellular medium was significantly increased by exposure to IL-6, but not by exposure to IL-2 or IL-8. 6. IL-2, IL-6 and IL-8 showed no effects on the release of nitrite, a stable metabolite of nitric oxide (NO), from VSMC. 7. These results indicate that IL-6, not IL-2 or IL-8, is a potent inhibitor of the alpha-adrenergic-stimulated contraction of vascular smooth muscle and its action is mediated by the increased synthesis of prostacyclin rather than NO.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Familial atrioventricular heart block of adult onset: electrocardiogram and HLA typing analysis.

A family was investigated because of heart block and sinus arrhythmia. The electrical characteristics were: (1) adult onset in all members; (2) complete heart block with atrial fibrillation in 2, and first- or second-degree heart block in 7 members; and (3) sinus arrhythmia in 3 members. Human leukocyte antigen (HLA) typing was performed. HLA A2, B39, Cw7, and DR12 were positive in 4 of 5 members in the heart block group. In the sinus arrhythmia group, HLA DR12 was positive in all members. In the normal group, none of these HLA typings was positive except one. These findings indicate a tighter relationship between heart block and the HLA locus than previously thought.

Adult↗
PubMed1995

[An outbreak of acute pulmonary histoplasmosis among travelers to a bat-inhabited cave in Brazil].

Histoplasmosis is known to be endemic in various parts of the world, especially in North and Latin America. In Japan, Histoplasma capsulatum has rarely been isolated from the natural environment. To date, only seven cases of histoplasmosis have been reported in Japan including some that were contracted in foreign countries. Herein, we report the occurrence of acute histoplasmosis among Japanese travelers who were exposed to bat guano in a cave near Manaus, Brazil. A group of 8 Japanese travelers entered a cave for a total of 2 hours in March, 1993. All the visitors had been healthy and had no history of abnormal chest roentgenograms. From 10 to 20 days after the exposure, 7 (87.5%) of the 8 individuals developed abnormal symptoms including fever, malaise, loss of appetite, myalgia, arthralgia, chest pain and dry cough. Five (62.5%) had nodular infiltrative shadows with or without hilar lymphadenopathy in the chest roentgenograms. Eight (100%) of the individuals showed serologic evidence of histoplasmosis. Despite the small number of subjects, this high rate of infection may be related to the fact that the subjects stayed in an enclosed area where air exchange was minimal, at the end of a deep cave infested with numerous bats. The cave involved has never been documented as being endemic for histoplasmosis. The threat of H. capsulatum infection in bat-inhabited caves should be emphasized to travelers and also to physicians.

Adult↗
PubMed1995

[Comparison of amplified Mycobacterium Tuberculosis Direct Test (MTD), Amplicor Mycobacteria kit (Amplicor) and PCR method for detection Mycobacterium tuberculosis in clinical specimens].

Accuracy amplified Mycobacterium Tuberculosis Direct Test (MTD), Amplicor Mycobacteria kit (Amplicor) and PCR method routinely used in the University of Tokyo Hospital (J. Clin. Microbiol. 31: 446-450 1991) were evaluated and compared with the same samples. The detection limits of MTD, Amplicor and PCR method (University of Tokyo) were 0.01-0.1 CFU/tube, 0.625 CFU/tube and 0.2 CFU/tube respectively, which were almost the same. These were shown to be at least as sensitive as the conventional culture techniques. The Tokyo Univ. method using radioisotope, takes up to 3 days, on the other hand 2 kits take 4-5 hours. These kits become useful tools for the early and rapid detection of M. tuberculosis in uncultured clinical specimens. But the risk of laboratory contamination and false-positive results remain. These must be further improved.

Bacteriological Techniques↗
PubMed1995

[Study on azithromycin in treatment of diffuse panbronchiolitis].

In the treatment of diffuse panbronchiolitis, azithromycin (AZM), a new macrolide antibiotic with 15-membered lactone ring, was studied for its efficacy and safety. AZM, 250 mg, was intermittently administered to a total of 60 patients twice a weeks, for 3 months as a rule, and its efficacy was clinically evaluated in 52 patients and the safety in 55. The rate of efficacy was 84.6% (44/52). Clinical findings 12 weeks after the start of administration showed a decrease in sputum volume in 30 of 46 patients and amelioration of dyspnea on exertion in 23 of 46 patients, and no worsening of symptoms was observed in the patients. Vital capacity (4/22), FEV1.0 (6/21), cold agglutination reaction (22/28), and CRP (16/36) were also improved. The rate of eradication of organisms isolated from the sputum except for indigenous organisms was 39.5% (15/38); 4 of the 22 strains of Pseudomonas aeruginosa were eradicated. Adverse reactions were observed in 4 of the 55 patients (7.3%), 1 patient each with rash, itching, diarrhea, and a gastric symptom (heavy feeling in the stomach). 4 of the 54 patients (7.4%) exhibited abnormal changes in clinical laboratory test values values. These were an increase in eosinophil count in 2, elevation of GOT in 1, and elevation of Al-P in 1. These adverse reactions and abnormal changes in laboratory tests were mild or moderate. Therefore, long-term intermittent administration of AZM, twice a week, is expected to have the same effect in the treatment of diffuse panbronchiolitis as long-term small-dose administration of 14-membered macrolides such as erythromycin and clarithromycin, whose effects have already been established.

Adolescent↗
PubMed1995

Successful treatment of Pneumocystis carinii Pneumonia in mice with benanomicin A (ME1451).

Benanomicin A (BNM-A) has antimycotic activities via binding to mannan in the cell walls of fungi. Anti-Pneumocystis carinii activity of the agent was examined in the P. carinii-infected BALB/c nu/nu female mouse model because P. carinii also possesses mannan in the membranes. The infected mice were treated with intraperitoneal injections of six doses of BNM-A (1, 2.5, 5, 10, 30, and 100 mg/kg of body weight), 4 mg of pentamidine isethionate per kg, 100 mg of sulfamethoxazole per kg combined with 20 mg of trimethoprim per kg (co-trimoxazole), or saline for 21 days. Each dosage group consisted of 10 mice. During treatment, five mice in the control group (saline) died, whereas 8 to 10 mice in all treatment groups survived. Almost the same efficacies were obtained for the groups treated with 5 mg or more and 10 mg or more of BNM-A per kg regarding the weight and number, respectively, of cysts found in the lungs as were obtained for the groups treated with pentamidine isethionate and co-trimoxazole. Overall, a dose of 10 mg of BNM-A per kg was effective against P. carinii pneumonia infection in the mice. Thus, BNM-A is a good candidate for a novel treatment for P. carinii pneumonia as a compound with a new mechanism of action against P. carinii.

Animals↗
PubMed1995

Immune complex transfer enzyme immunoassay that is more sensitive and specific than western blotting for detection of antibody immunoglobulin G to human immunodeficiency virus type 1 in serum with recombinant pol and gag proteins as antigens.

Antibody immunoglobulin G (IgG) to human immunodeficiency virus type 1 (HIV-1) in serum was detected by ultrasensitive enzyme immunoassays (immune complex transfer enzyme immunoassays) with recombinant reverse transcriptase (rRT), p17 (rp17) and p24 (rp24) of HIV-1 as antigens and beta-D-galactosidase from Escherichia coli as the label. The immune complex, comprising 2,4-dinitrophenyl-bovine serum albumin-recombinant protein conjugate, antibody IgG to HIV-1, and recombinant protein-beta-D-galactosidase conjugate, was trapped on polystyrene beads coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG, eluted with epsilon N-2,4-dinitrophenyl-L-lysine, and transferred to polystyrene beads coated with affinity-purified (anti-human IgG gamma-chain) IgG. Bound beta-D-galactosidase activity was assayed by fluorometry. The assays were highly reproducible with no serious serum interference, and they were much more sensitive than Western immunoblotting for the corresponding antigens. Signals with rRT, rp17, and rp24 for asymptomatic carriers were at least 56,000-, 680-, and 22-fold higher, respectively, than those for seronegative individuals, and neither indeterminate nor false-positive results were observed, whereas some serum samples were false negative or false positive by Western blotting for p17 and/or p24 antigen. In some cases, seroconversion was detected earlier than by conventional methods. Therefore, these assays are suggested to be more useful than conventional methods not only for the confirmation of antibody IgGs to RT, p17, and p24 of HIV-1 in serum but also for the detection of seroconversion.

Antigen-Antibody Complex↗
PubMed1995

Measurement of human immunodeficiency virus type 1 p24 in serum by an ultrasensitive enzyme immunoassay, the two-site immune complex transfer enzyme immunoassay.

Human immunodeficiency virus type 1 (HIV-1) p24 antigen was measured by an ultrasensitive enzyme immunoassay (two-site immune complex transfer enzyme immunoassay). The antigen was reacted simultaneously with 2,4-dinitrophenyl-biotinyl-bovine serum albumin-anti-recombinant p24 (rp24) Fab' conjugate and anti-rp24 Fab'-beta-D-galactosidase conjugate. The complex that was formed, comprising the three components, was transferred from polystyrene beads coated with affinity-purified (anti-2,4-dinitrophenyl group) immunoglobulin G (IgG) to polystyrene beads coated with streptavidin. The detection limit of rp24 was 2.4 fg (0.1 amol) per assay or 0.24 pg/ml with as little as 10 microliters of serum. When sera were treated at low pH, p24 was detected in 34 (68%) of 50 serum samples from asymptomatic carriers, in 25 (86%) of 29 serum samples from patients with advanced HIV-1 infection, and in none of 117 serum samples from HIV-1-seronegative individuals. Levels of p24 in serum were inversely correlated to those of anti-HIV-1 p24 IgG, and the recovery of rp24 added to serum decreased to zero with increasing levels of anti-HIV-1 p24 IgG in serum. This sensitive method may be used as a powerful tool for investigating the disease.

Antigen-Antibody Complex↗
PubMed1995

Monocyte chemoattractant protein 1 inhibits growth of rat vascular smooth muscle cells.

The early atherosclerotic lesion is characterized by the migration of inflammatory cells, including monocytes, which may serve as a source of cytokines such as monocyte chemoattractant protein 1 (MCP-1), a homologue of mouse JE. We investigated the effect of MCP-1 on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortae. In Northern blot analysis, MCP-1/JE transcripts were not observed in unstimulated VSMC, but its expression was clearly observed by exposure to lipopolysaccharide (1 micrograms/ml) for 6 h. Human recombinant MCP-1 inhibited the uptake of [3H]thymidine by VSMC cultured in 0.5% fetal bovine serum (FBS) containing Dulbecco's modified Eagle's medium (DMEM) in a dose-dependent manner. The inhibitory effect of MCP-1 on the growth of VSMC was also confirmed by a change in cell counts. The antiproliferative effect of MCP-1 was significantly blocked in the presence of an anti-MCP-1 antibody. MCP-1-induced inhibition of [3H]thymidine uptake was not affected in the presence of indomethacin (1 micrograms/ml) or NG-monomethyl-L-arginine (0.1 mM), and MCP-1 showed no effect on 6-ketoprostaglandin F1 alpha, guanosine 3',5'-cyclic monophosphate, and adenosine 3',5'-cyclic monophosphate syntheses in VSMC. These results indicate that MCP-1 inhibits the proliferation of VSMC in vitro and that its effect is independent of prostaglandin or nitric oxide generation.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Multiple saccular aneurysm formation in a patient with bilateral coronary artery fistula: a case report and review of the literature.

We describe a case of bilateral coronary artery fistula originating from the left anterior descending and right coronary arteries which showed multiple saccular aneurysm formation. Although saccular aneurysm formation in patients with bilateral coronary artery fistula is extremely rare, only 3 similar cases having been reported before, it shows two distinctive features upon coronary angiography: multiplicity and origin in the left fistulous coronary artery.

Adult↗
PubMed1995

Suppressive role of endogenous endothelial monocyte chemoattractant protein-1 on monocyte transendothelial migration in vitro.

Monocyte chemoattractant protein-1 (MCP-1, or monocyte chemotactic and activating factor) is thought to play an important role in monocyte infiltration into tissue, but little is known about its effect on monocyte-endothelium interaction. We examined the effect of MCP-1 produced by cytokine-activated endothelial cells (ECs) on monocyte-endothelium adhesion and subsequent transendothelial migration by using a double-chamber vessel model. Unstimulated ECs showed no MCP-1 expression, but exposure to interleukin-1 beta (IL-1 beta, 25 U/mL) induced marked MCP-1 mRNA expression and protein synthesis. When placed in the lower compartment, recombinant human (rh) MCP-1 (100 ng/mL) produced a 1.9-fold and a 2.7-fold increase in adhesion and migration, respectively, compared with a corresponding 51% and 59% decrease when placed in the upper compartment. Migration of monocytes was dependent on a gradient of rh-MCP-1 from the apical to basilar side of the EC layer. Furthermore, a forward gradient of MCP-1 induced adherent cells to increase their subsequent migration, whereas a reverse gradient induced the cells to detach and completely inhibited their subsequent migration. Pretreatment with IL-1 beta for 4 and 24 hours produced a 20% and 63% increase in monocyte migration, respectively. In the presence of anti-MCP-1 antibody, the increase was further enhanced by 52% and 152%, respectively. These results suggest that endogenous endothelial MCP-1, when secreted by IL-1-stimulated ECs, suppresses monocyte migration in the presence of MCP-1 on the basilar side of the EC layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1995

Induction of monocyte chemoattractant protein-1 synthesis in human monocytes during transendothelial migration in vitro.

Monocyte chemoattractant protein-1 (MCP-1, or monocyte chemotactic and activating factor) plays important roles in the recruitment of monocytes and thus in the development of atherosclerosis. In this study, we determined whether MCP-1 synthesis was induced by the cellular interaction between monocytes and endothelial cells during the process of transendothelial migration. We found that when human peripheral blood monocytes (2.5 x 10(6) cells) and umbilical vein endothelial cells (HUVECs; 5.0 x 10(5) cells) were cocultured for 5 hours, 7.9 ng/mL MCP-1 was secreted into the medium, whereas when the two were cultured separately, MCP-1 levels were 1.0 and 0.9 ng/mL, respectively. Furthermore, the use of interleukin-1 beta (IL-1 beta)-pretreated HUVECs in cocultures induced twice the levels of MCP-1 as in unstimulated HUVEC culture. Conditioned medium had transendothelial chemotactic activity for monocytes, and this activity was completely abolished by addition of anti-MCP-1 antibody. Although MCP-1 mRNA levels were very low or undetectable in HUVECs or monocytes alone, message could be detected after 2 hours of coculture in total mRNA preparations from both monocytes and HUVECs. mRNA levels increased by 4 hours and had declined slightly by 24 hours. The rapid induction of message suggests that cell contact between monocytes and HUVECs induces the de novo synthesis of MCP-1 protein. Anti-interleukin (IL)-1 alpha/beta and anti-tumor necrosis factor-alpha antibodies, or anti-lymphocyte function-associated antigen-1 and very late antigen-4 antibodies, had little or no inhibitory effects on MCP-1 secretion by cocultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion Molecules↗
PubMed1995

High-performance liquid chromatographic determination of cholesterol and cholestanol in human serum by precolumn derivatization with 2-[2-(isocyanate)ethyl]-3-methyl-1,4-naphthoquinone combined with platinum catalyst reduction and electrochemical detection.

The precolumn derivatization reagent, 2-[2-(isocyanate)ethyl]-3-methyl- 1,4-naphthoquinone (IMQ) was applied to the simultaneous determination of cholesterol and cholestanol in human serum by HPLC with electrochemical detection. The compounds extracted with hexane from human serum, to which was added 1-eicosanol as an internal standard, were reacted with IMQ in acetone and converted into the corresponding carbamic acid esters. After chromatographic separation of the derivatives, they were reduced once in a platinum catalyst reduction column connected on-line, then quantified with an electrochemical detector in the oxidation mode. The detection limits at a signal-to-noise ratio of 3 were 6.6 pg (17 fmol) and 7.4 pg (19 fmol) for cholesterol and cholestanol, respectively in a 10 microliter injection volume. This method was successfully applied to the determination of free and total cholesterol and total cholestanol in normal human serum, and the concentrations of free and total cholesterol were compared with those obtained by an enzymatic method.

Cholestanol↗