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Biomedical subjects

A Kawamura

Publications and source records attributed to A Kawamura.

At least 73 records · Page 4Linked to original sources

Over expression of mitochondrial citrate synthase gene improves the growth of carrot cells in Al-phosphate medium.

A mitochondrial citrate synthase (CS) of Arabidopsis thaliana was introduced into carrot (Daucus carota L. cv. MS Yonsun) cells by Agrobacterium tumefaciens-mediated transformation. Transgenic cell lines had high CS activity, the highest value observed was 0.24 mumol (mg protein)-1 min-1 which was 1.9-fold of that in wild-type cells. Transcript levels of DcCS were similar between transgenic lines, but those of AtCS were increased as the CS activity of cells was increased. Isoelectric focussing revealed that the CS polypeptide of the transgenic lines had a pI value different from that of the wild-type cells, although the molecular mass was the same. These results indicate that the CS polypeptides of A. thaliana were expressed and processed to the mature form in carrot cells. The growth rate and excretion was 2.2-2.8 and 2.8-4.0 fold greater in the transgenic cells than in the wild type cells, respectively. Phosphate uptake from Al-phosphate also increased in transgenic cells. It appears, the overexpression of mitochondrial citrate synthase in carrot cells improves the growth rate in Al-phosphate medium possibly as a result of increased citrate excretion.

Agrobacterium tumefaciens↗

Clinical presentation of tuberculosis in culture-positive children. Pediatric Tuberculosis Consortium.

BACKGROUND: Because tuberculosis (TB) in children implies recent infection, children serve as sentinels for disease transmission within a community. Despite the significance of diagnosing tuberculosis in children, most cases are diagnosed on clinical evidence rather than laboratory findings. METHODS: We analyzed the demographic and clinical presentation of 156 children with culture proven tuberculosis using Epi-Info Version 6. RESULTS: Although the clinical characteristics of this population were generally consistent with those seen in previous studies, several unexpected results were observed. Boys were overrepresented in the group of very young children (72% < 1 year). Many of the children had coexisting diseases not known to predispose to TB (37%). Cavitation, usually observed in older children, was seen in four children < or = 1 year of age. Few children were homeless or HIV-infected, but many (42%) lived in female-headed households. Of the adult contacts at risk for TB, many (49%) were recent immigrants to the US. Overall 34% of the population was either foreign born or the children of recent immigrants. CONCLUSIONS: This series of 156 culture-positive children provides an understanding of the risk factors and clinical presentation of pediatric tuberculosis. The data emphasize the impact of the child's environment on the risk for tuberculosis.

Adolescent↗

Abnormal coronary flow profiles at rest and during rapid atrial pacing in patients with hypertrophic cardiomyopathy.

To examine the mechanism of myocardial ischemia in hypertrophic cardiomyopathy (HCM), coronary flow velocity was measured in the left anterior descending coronary artery (LAD) using a Doppler guide wire in 11 patients with HCM and in 8 normal controls. The average peak velocity (APV), percent increase of APV (%APV), and APV during systole (Vs) and diastole (Vd) were calculated at rest and during rapid atrial pacing. The APV in HCM reached a peak value at a heart rate of 90 beats/min, while in the controls the APV increased continuously until the heart rate reached 130 beats/min [%APV (130 beats/min); 103+/-30% in HCM vs 139+/-23% in controls, p<0.04]. During rapid atrial pacing, Vs in the controls increased, whereas Vs in HCM decreased further. During high-rate pacing, Vd in HCM reached a peak value at a heart rate of 90 beats/min, whereas in the controls, Vd increased continuously until the heart rate reached 130 beats/min. The acceleration rate of early diastolic flow was significantly lower in HCM than in the controls (1.85+/-0.66 vs 3.18+/-1.62 m/s2, p<0.03). This abnormal response might be due to an increase in the reverse systolic flow and a decrease in the diastolic flow, probably caused by a slow acceleration of early diastolic flow velocity in the LAD.

Adult↗

The disposition of 14C-labeled tacrolimus after intravenous and oral administration in healthy human subjects.

Tacrolimus is a macrolide lactone with potent immunosuppressive properties. It has been shown in clinical studies to prevent allograft rejection. The pharmacokinetics of tacrolimus in healthy subjects and transplant patients has been described in earlier studies using immunoassay methods; however, detailed information on the absorption, distribution, metabolism, and excretion of tacrolimus using a radiolabeled drug is lacking. The objective of the present study was to characterize the disposition of tacrolimus after single i.v. (0.01 mg/kg) and oral (0.05 mg/kg) administration of 14C-labeled drug in six healthy subjects. Tacrolimus was absorbed rapidly after oral dosing with a mean Cmax and Tmax of 42 ng/ml and 1 h, respectively. The oral bioavailability was about 20%. After i.v. and oral dosing, most of the administered dose was recovered in feces, suggesting that bile is the principal route of elimination. Urinary excretion accounted for less than 3% of total administered dose. In systemic circulation, unchanged parent compound accounted for nearly all the radioactivity; however, less than 0.5% of unchanged drug was detectable in feces and urine. The excretion of the metabolites was formation-rate-limited. The mean total body clearance at 37.5 ml/min was equivalent to about 3% of the liver blood flow. Renal clearance was less than 1% of the total body clearance. The mean elimination half-life was 44 h.

Administration, Oral↗

Importance of left anterior descending coronary artery curvature in determining cross-sectional plaque distribution assessed by intravascular ultrasound.

We assessed the relation between the circumferential distribution of coronary atherosclerotic plaques and the structure of the epicardial coronary arteries in patients with coronary artery disease using intravascular ultrasound in vivo. Coronary atherosclerosis preferentially formed at the inner arc of the curved coronary vessels, and greater vessel curvatures were associated with greater distributions of atherosclerotic lesions along the inner coronary artery wall.

Adult↗

Pharmacokinetics and pharmacodynamics of FK143, a nonsteroidal inhibitor of steroid 5 alpha-reductase, in healthy volunteers.

The pharmacokinetics and pharmacodynamics of FK143, a new nonsteroidal inhibitor of steroid 5 alpha-reductase, were investigated in healthy volunteers, with use of plasma FK143 concentrations and serum dihydrotestosterone levels as an index for pharmacologic effects. The area under the plasma concentration-time curve from zero to infinity [AUC(0-infinity)] and maximum plasma concentration [Cmax] were increased dose proportionally after oral administration (100 to 500 mg) while subjects were in the fed state. The AUC(0-infinity) and Cmax after 500 mg oral administration during fed conditions were significantly larger than those during the fasted state, suggesting an increase of the absorption of FK143. Dihydrotestosterone concentrations after a single administration of FK143 (100 to 500 mg) during fed conditions decreased to about 65% of predose values and thereafter slowly recovered to the same levels as predose values at 168 hours. A combined pharmacokinetic-pharmacodynamic model was constructed with use of changes in dihydrotestosterone concentrations. The pharmacokinetic-pharmacodynamic profiles of FK143 after repeated administration were predictable with use of the pharmacokinetic-pharmacodynamic parameters obtained after a single administration of FK143.

5-alpha Reductase Inhibitors↗

Enhancement of retroviral gene transduction on a dish coated with a cocktail of two different polypeptides: one exhibiting binding activity toward target cells, and the other toward retroviral vectors.

CH-296, a recombinant fragment of human fibronectin (FN) composed of the cell-binding domain (C-domain), heparin-binding domain II (H-domain), and CS1 site, enhances the retrovirus-mediated gene transduction (GT) of hematopoietic stem cells. The RGD sequence in the C-domain is recognized by a variety of cell types through integrin VLA-5, and the LDV sequence in the CS1-site is recognized by integrin VLA-4. Retrovirus particles were also found to bind to the H-domain. Consequently, the CH-296 fragment can enhance GT through binding to both retrovirus particles and target cells that express integrins VLA-5 and/or VLA-4. In this study, we found that the GT efficiency can be maintained at levels comparable to that of CH-271, a FN fragment similar to CH-296 but lacking the CS1 site, when a cocktail of separated functional domains of CH-271 is used. When a dish was coated with a mixture of the C-domain and H-domain (molar ratio, 1:10), the GT efficiency of NIH3T3 cells reached the same level as that of the mother fragment, CH-271. The H-domain in the cocktail can be replaced with other virus-binding components, polylysine, FGF, and the insulin-binding domain of ColV, without the loss of GT efficiency. With other than FN fragments, a cocktail of erythropoietin and polylysine caused higher GT efficiency of Epo-receptor expressing TF-1 cells than in the case of each component alone.

Animals↗

Immunomodulation in transplant patients by cryofiltration.

Cryofiltration was applied to major ABO incompatible bone marrow transplant (BMT), renal transplant, and chronic renal rejection cases. The anti-ABO titers IgM and IgG pretreatment by cryofiltration were x64 and x8 in a major ABO incompatible BMT patient. After treatments, they were decreased to x16 and x2, respectively. BMT was performed successfully. In a case of ABO major incompatible renal transplant, anti-A-IgM before cryofiltration treatment was x128, and CH50 was 26.5. Three treatments were performed. As a result, the anti-A-IgM and CH50 levels were decreased to x4 and under 10. After renal transplantation, antibodies appeared again, but because the creatinine level was normal, cryofiltration was not performed again. Five cases of chronic rejection of renal transplants were treated by cryofiltration. They remained hemodialysis (HD) free for an average of 17.4 months, and the longest duration was 32 months. Cryofiltration is a good treatment for extracorporeal immunomodulation in transplantation.

ABO Blood-Group System↗

Basic clinical study of an easy and effective leukocytapheresis by the use of nonwoven polyester filter.

Leukocytapheresis (LCAP) is widely used for the treatment of immunological diseases. We studied a new treatment of LCAP using a nonwoven polyester filter. In a basic study, 30-70% of the lymphocytes were adsorbed. Also, 30-68% of the lymphocyte subsets were removed. This method was applied to 2 patients with corticosteroid-resistant active ulcerative colitis. Erosion, edema, bleeding, ulcer formation, and stenosis of the colon were almost completely repaired after 6 LCAP treatments. LCAP using a nonwoven polyester filter will be a very useful treatment for immunological diseases and extracorporeal immunomodulation.

Adult↗

Cryofiltration apheresis for major ABO-incompatible kidney transplantation.

The barrier of ABO-incompatible kidney transplantation is the presence of anti-A and anti-B antibodies in the recipient's circulating blood. Double filtration plasmapheresis (DFPP) is usually used to eliminate those antibodies. We tried cryofiltration apheresis (CRYO) in 2 recipients. Patient 1 was a 45-year-old male with B, Rh(+). The titers of IgM anti-A antibody were only reduced from x64 to x32 by the end of 3 sessions of standard CRYO. Renal allografting was not performed. Case 2 was a 29-year-old male with B, Rh(+). CRYO was introduced for 3 sessions. The initial IgM and IgG titers were x128 and negative, respectively. The standard CRYO system was modified by temperature, treated volume, and filter pore size. The IgM anti-A antibody titer was markedly reduced to x2 after the final session of CRYO. The donor was a 56-year-old father with A, Rh(+). Tacrolimus, azathioprine, methylprednisolone, and antilymphocyte globulin were used as the introductory immunosuppression therapy.

ABO Blood-Group System↗

Effect of dexamethasone on cell proliferation of neuroepithelial tumor cell lines.

The effect of glucocorticoid on cell proliferation, the expression of glucocorticoid receptor, and the relationship between inhibition of cell growth and apoptosis were investigated in four established neuroepithelial tumor cell lines (KNS42, T98G, A172, and U251MG). Glucocorticoid receptor expression was located in the cytoplasm of untreated cells, but translocated into nuclei after treatment with dexamethasone in KNS42, T98G, and A172 cells. U251MG did not express glucocorticoid receptors. Dexamethasone significantly inhibited the growth of KNS42 and T98G cell lines, at high concentrations in contrast to growth stimulation at low concentration. Dexamethasone inhibited proliferation of A172 cell line at all concentrations from 10(-4) M to 10(-7) M. These were prevented by RU38486, a specific glucocorticoid antagonist. Apoptosis did not occur in any cell lines after dexamethasone treatment. There was no response to glucocorticoid by U251MG cells. Dexamethasone treatment of neuroepithelial tumor cells expressing glucocorticoid receptors causes translocation into the nucleus to modulate cell proliferation upon binding of different concentrations of dexamethasone in vitro. Dexamethasone inhibits proliferation of some neuroepithelial cell lines, not by glucocorticoid-induced apoptosis. The bimodal potential of glucocorticoid to stimulate or suppress proliferation of neuroepithelial tumor cells expressing glucocorticoid receptor must be considered in clinical trials.

Cell Division↗

Morphological variation of the frontal sinus in Melanesian (Fiji) and Polynesian (Western Samoa) populations.

The aims of this study were to investigate gender differences in frontal sinus morphology and to estimate differences between Fijian and Western Samoan populations. Cephalograms of 118 Fijians (59 male, 59 female), 80 W. Samoans (33 male, 47 female) and 89 Japanese (60 male, 29 female) were used in this study. The thickness of the frontal sinus and the convexity of glabella in males were found to be larger than those of females in each population. The angle of Sg-N-G in the Fijians was larger than that of the Western Samoans and Japanese. In order to compare the frontal sinus morphology among populations, Mahalanobis' generalized distances were calculated on the basis of the five distance diameters. The results indicate that gender is separated by the first axis which indicates the overall size. Japanese samples were separated from South Pacific samples by the second axis which indicates the shape factor. In populational discrimination, there was a higher percentage of correct discriminations of the females of the males. In conclusion, gender difference was recognized in the size of the frontal sinus, and the populational differences were shown in the shape factor between Melanesian and Polynesian populations, and also between South Pacific and Japanese populations.

Adolescent↗