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Biomedical subjects

T Okano

Publications and source records attributed to T Okano.

At least 307 records · Page 17Linked to original sources

[Incidence of renal cell carcinoma in Chiba Prefecture, Japan; ten years experience].

Many reports about the increase of renal cell carcinoma patients have been published in Japan recently, however, the real fluctuations in the total number of patients in relation to the change of population have not been reported yet. Most of the patients with renal cell carcinoma in the last 10 years were examined in Chiba prefecture, which has a population of about five million and 25 active urological offices. Histologically confirmed cases were investigated by sending questionnaire letters. The items were as follows; sex, age, address, occupation, family history, past history, symptoms, examination methods that first detected the tumor, operation date, tumor diameter and clinical stage. Twenty two offices returned answers and 560 cases who lived in Chiba were found to have renal cell carcinoma from 1980 to 1989. Yearly incidence rates per 100,000 persons demonstrated a significant increase from 0.32 to 2.07. Small, asymptomatic and low stage cancers have been increasing rapidly, however, the rate of metastatic disease has not shown any decrease. The main cause of rapid increase seems to be attributed to progress in diagnostic methods and increase of early detection, but the possibility of an increase in some carcinogenic factors can not be ruled out.

Adult↗

[Studies of lymphocyte activation on late asthmatic response in adult asthma].

Late asthmatic response (LAR) as well as delayed asthmatic response (DeAR) is an important clinical characteristic in adult severe asthma. These responses might be based on cell to cell interaction following lymphocyte activation. Therefore, to clarify the pathogenesis of LAR, we studied the lymphocyte functions of adult asthmatics with LAR provoked by inhalation of house dust and Candida antigen. The results revealed that mite antigen-specific lymphocyte blastogenesis, IL-2 and ECF production were significantly higher in asthmatics with LAR provoked by house dust antigen than in normal subjects and asthmatics with IAR by house dust and LAR by Candida, though there was no significant difference in NCF. Candida antigen-specific lymphocyte blastogenesis, IL-2, ECF and NCF production were significantly higher in asthmatics with LAR provoked by Candida antigen than in normal subjects and asthmatics with IAR or LAR provoked by house dust. There was a positive correlation between Candida antigen-specific IL-2 and NCF production in asthmatics with LAR provoked by Candida antigen. These results suggest that antigen-specific lymphocyte activation may play an important role in the pathogenesis of LAR, especially in asthmatics with LAR provoked by Candida antigen, and that LAR and DeAR should be considered inclusively as cell-mediated allergy.

Adolescent↗

[Clinical evaluation of endoscopic injection sclerotherapy and esophageal transection].

We investigated the effects of EIS and esophageal transection on treatment of esophageal varices and the late result of EIS treatment group with that of surgical treatment group. One hundred and forty-seven patients underwent esophageal transection and 244 patients injection sclerotherapy in our institute. 1. The 5-year cumulative survival rate in patients with EIS was 58%, while 62% in those with transection. 2. Judging from the findings of varices after treatment which showed the negative red color sign, or changes from F2 or F3 to F1, the effect of two methods were 72% in operation group and 73% in EIS group, respectively. 3. There was no significant difference in the rates of rebleeding between EIS (7.8%) and operation (10.2%) groups. 4. Prognosis of esophageal varices treated with EIS or operation was considered to depend on the Child's classification. We conclude that endoscopic sclerotherapy should be considered to be the first choice of treatment for esophageal varices.

Adolescent↗

In vivo protein adsorption on polymers: visualization of adsorbed proteins on vascular implants in dogs.

The absorption of plasma proteins is an important event at the blood-material interface, and strongly affects subsequent cellular interaction and thrombus formation. Although considerable efforts have been expended to elucidate the mechanism of protein adsorption and the role of absorbed protein layer at the blood-material interface, there has been little knowledge of how the initial adsorbed proteins are maintained or changed in a time-variant process in in vivo long-term implantation. In this study, we described detailed analyses concerning the characterization of adsorbed proteins on HEMA--styrene block copolymer surfaces (HEMA-st) and poly(ethylene oxide) (PEO) grafted Biomer (B-PEO4K) for in vivo long-term canine vascular graft implants as well as in vitro short-term experiments. Biomer vascular grafts (6 mm I.D., 7 cm in length) were fabricated by a dip coating and the luminal surface was modified with PEO grafting, HEMA-st coating, or Biomer coating (control). These surface modified grafts were recirculated for different time intervals (5, 15, 30, 60 and 120 min) using citrated canine whole blood. The grafts were then implanted in the abdominal aortas of dogs and evaluated for graft patency and protein adsorption. The adsorbed proteins (albumin, IgG and fibrinogen) were quantified using an in situ radioimmunoassay. Surface protein layer thickness was measured by transmission electron microscopy (TEM). Visualization of absorbed plasma proteins (albumin, IgG and fibrinogen) was performed with TEM using an immunoperoxidase double antibody technique. In in vitro recirculation systems, albumin and IgG showed similar Langmuir type pattern onto all test surfaces. On B-PEO4K surfaces, fibrinogen adsorption kinetics demonstrated 'Vroman effect'. The Biomer and B-PEO4K grafts occluded within 1 month, while HEMA-st grafts were patent for over 3 months. Biomer and B-PEO4K showed thick multilayers of adsorbed proteins, and the thickness increased with implantation periods and the composition altered with time. In contrast, HEMA-st showed a monolayer-like adsorbed protein pattern, and the composition and thickness were consistent regardless of implantation time including in vitro short-time experiments, which may attribute to less conformational change of adsorbed proteins on HEMA-st surfaces. In terms of nonthrombogenicity, the stable monolayer-like adsorbed protein layer on HEMA-st surfaces exhibited improved blood compatibility over thick multilayered adsorbed proteins on Biomer and B-PEO4K surfaces.

Adsorption↗

[Aqueous protein concentration after vitrectomy for diabetic retinopathy].

The protein concentration in the aqueous humor in 46 eyes with proliferative diabetic retinopathy was quantitated before and after vitrectomy. Before surgery, the protein value as measured by a laser flare-cell meter was 5 times that in normal control eyes. The value was elevated on day 3 after surgery and gradually decreased to reach the preoperative value 1 month after surgery. The postoperative protein value significantly increased in accordance with the complexity of surgical maneuvers until day 17 when the 46 eyes were classified into 3 groups: simple-maneuver group (12 eyes), membrane delamination group (18 eyes) and silicone oil group (16 eyes). The time course of aqueous protein concentration in the simple-maneuver group was similar to that after vitrectomy for vitreous hemorrhage in 8 eyes with prior branch retinal vein occlusion. The observed increase in aqueous protein after vitrectomy seemed to be transferred from vitreous cavity to anterior chamber.

Adult↗

[Clinical significance of anti-nucleolar antibodies detected by immunoprecipitation method in patients with systemic sclerosis].

We have characterized a clinical significance of anti-U3RNP, anti-7-2RNP, anti-RNA polymerase I and anti-PM-Scl antibody, autoantibodies to nucleolar proteins detected by immunoprecipitation method in patients with systemic sclerosis (SSc). In 248 patients with SSc, anti-U3RNP antibody was positive in 9 (3.6%), anti-7-2RNP antibody was positive in 7 (2.8%) and anti-RNA polymerase I antibody was positive in 3 (1.2%). But none of 248 patients was positive for anti-PM-Scl antibody. Anti-U3RNP antibody positive SSc patients showed significantly lower frequency of joint and lung involvements, compared with anti-U3RNP antibody negative SSc patients. Anti-7-2RNP antibody was found only in patients with limited scleroderma. The anti-7-2RNP antibody could be detected before appearance of skin thickening, so this indicate the usefulness of detecting anti-7-2RNP antibody in the early stage of SSc. Two of 3 anti-RNA polymerase I antibody positive patients were classified as diffuse scleroderma. All anti-RNA polymerase I antibody positive patients had high incidence of internal organ involvements including lung, heart and kidney, so two of these patients died of heart failure. These data showed the close clinical association of antigenic specificities of anti-nucleolar antibodies analysed by immunoprecipitation method, and indicated the usefulness of detecting these anti-nucleolar antibodies in subgrouping of patients with SSc.

Adult↗

H+ coupled active transport of bestatin via the dipeptide transport system in rabbit intestinal brush-border membranes.

Bestatin [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine], a dipeptide containing an unusual amino acid, has been used clinically as an anticancer agent in p.o. dosage form. We examined the transport characteristics of [3H]bestatin by rabbit intestinal brush-border membrane vesicles. Bestatin uptake was stimulated by an inward H+ gradient (overshoot phenomenon) and by an interior-negative membrane potential. About half of the apparent bestatin uptake at 1 mM by brush-border membrane vesicles was estimated as binding to the membranes. The affinity constant for the bestatin transport was 0.52 mM. The uptake of bestatin by brush-border membrane vesicles was inhibited by p.o. cephalosporins and dipeptides, but not by amino acids. In vesicles preloaded with either bestatin, cephradine or glycylsarcosine, the uptake of [3H]bestatin was stimulated markedly (countertransport effect). These results indicate that bestatin is transported via the H+/dipeptide transport system in rabbit intestinal brush-border membranes.

Aminopeptidases↗

Toxicity and antitumor activity against solid tumors of micelle-forming polymeric anticancer drug and its extremely long circulation in blood.

Toxicity and in vivo antitumor activity against five solid tumors (C 26, C 38, M 5076, MKN-45, MX-1) of Adriamycin (ADR)-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer (PEG-P[Asp(ADR)]) were evaluated, and its pharmacokinetic behavior in blood and biodistribution by i.v. injection were obtained. PEG-P[Asp(ADR)] was revealed to express higher antitumor activity than ADR against all the examined tumors except MKN-45. Especially against C 26, PEG-P[Asp(ADR)] expressed critical suppression of tumor growth and considerably prolonged life span of the treated mice. PEG-P[Asp(ADR)] was observed in blood at much higher concentrations with a longer half-life than ADR after the i.v. injection. PEG-P[Asp(ADR)] was known to form a micellar structure with a diameter of approximately 50 nm and a narrow distribution in phosphate-buffered saline. Therefore, the stabilized circulation of ADR residue in blood by binding to the block copolymer was considered to result from the micellar structure which possesses the hydrated outer shell composed of the poly(ethylene glycol) chains.

Animals↗

Design of 9-beta-D-arabinofuranosyladenine (ara-A) transdermal delivery system for animal studies: regulation of drug concentration in vivo.

Transdermal delivery systems of 9-beta-D-arabinofuranosyladenine (ara-A), having controlling membranes of various permeabilities, were developed and applied to Azone-pretreated hairless mouse abdominal skin. It was confirmed that the blood concentrations of ara-A and its metabolite 9-beta-D-arabinofuranosylhypoxanthine (ara-H) in hairless mice are controlled by the permeability of the controlling membrane in the transdermal patch. Furthermore, these blood concentrations were found to closely agree with the values obtained from theoretical model calculations. Finally, but importantly, the "micropharmacokinetic" behavior of ara-A in cutaneous tissue could also be predicted. These results suggest that the transdermal patch may be employed in dermal and transdermal ara-A efficacy studies in the treatment of cutaneous herpes virus infections in hairless mice.

Administration, Cutaneous↗

The existence of 25-hydroxyvitamin D3-1 alpha-hydroxylase in the liver of carp and bastard halibut.

We have found that carp and bastard halibut contain 25-hydroxyvitamin D3 (25-D3)-1 alpha-hydroxylase in the liver besides in the kidney by the following in vivo and in vitro experiments. When [3H]-25-D3 was intraperitoneally injected to vitamin D(D)-deficient carp and normal bastard halibut (D-deficient bastard halibut could not be raised because they died during farming), the profiles of high-performance liquid chromatography (HPLC) of the plasma lipid extract showed the formation of a peak corresponding to [3H]-1 alpha,25-dihydroxyvitamin D3 (1,25-D3). When [3H]-25-D3 was incubated with liver homogenates of the fish, a peak corresponding to [3H]-1,25-D3 was also observed in the profile of HPLC. The formation of the metabolite was confirmed by the thermal isomerization into the pre-isomer and mass fragmentography. Although the 1 alpha-hydroxylase was also observed in the kidney, the activity of the enzyme was lower than that in the liver. The results suggest that 25-D3-1 alpha-hydroxylase exists in the liver of carp and bastard halibut and the 25-D3 formed from D3 in the liver is immediately metabolized into 1,25-D3 in the same tissue. The suggestion is supported by the fact that D3 is a major circulating compound with small amounts of 1,25-D3 in the fish while the plasma levels of 25-D3 are under the limit of detection.

24,25-Dihydroxyvitamin D 3↗

Endoscopic re-establishment of membranous urethral disruption.

A total of 17 patients with traumatic membranous urethral disruption underwent urethral reconstruction via a core-through technique. Followup was 1 to 8 years (mean 3.7 years) postoperatively, and included 6 weeks with an indwelling catheter, periodic dilation for 6 months and occasional sounding. Within 1 year postoperatively, 6 patients required additional scar incision, including 3 who underwent scar resection. At 1 to 8 years postoperatively 6 patients had complications: 3 had stricture requiring periodic dilation (including 2 who underwent scar incision), while 2 had mild stress incontinence and 1 had nocturnal enuresis. Traumatic impotence was noted in 7 patients but the operation was not the cause in any. This method of endoscopic management was found to be an acceptable alternative to urethroplasty in cases of membranous urethral disruption.

Adult↗

"On-off" thermocontrol of solute transport. II. Solute release from thermosensitive hydrogels.

Poly(N-isopropylacrylamide) (NIPAAm)/polytetramethylene ether glycol (PTMEG) interpenetrating polymer networks (IPNs) were synthesized and their feasibility as thermosensitive hydrogels for drug release was investigated. The release of indomethacin incorporated into these matrices showed pulsatile patterns in response to temperature changes and was sensitive to a few degrees of temperature fluctuation. The temperature inducing on-off release deviated from the gel collapse temperature of unloaded gel, possibly because of solute effects on network properties. The lag time and release profile of indomethacin in the low-temperature region (on process) of each temperature cycle were affected by the gel composition and applied temperature. The results of this study demonstrate that solute release can be regulated by rapid deswelling of the surface of the gels in response to temperature.

Drug Carriers↗

"On-off" thermocontrol of solute transport. I. Temperature dependence of swelling of N-isopropylacrylamide networks modified with hydrophobic components in water.

The swelling in water, as a function of temperature, of two series of N-isopropylacrylamide (NIPAAm) polymer networks was studied. In the first series, n-butylmethacrylate (BMA) was copolymerized with NIPAAm, and in the second, polytetramethylene ether glycol (PTMEG) was incorporated into NIPAAm network as a chemically independent interpenetrating network. With increasing BMA content in the poly(NIPAAm-co-BMA) network, the gel collapse point was lowered and the gels deswelled in a more gradual manner with increasing temperature. In the interpenetrating polymer networks (IPN) system, the gel collapse point was not significantly changed by the amount of incorporated PTMEG. In DSC thermograms of swollen samples, the shape and onset temperature of the endothermic peak corresponded to the gel deswelling behavior and gel collapse point. The temperature dependence of equilibrium swelling in water was shown to be a function of the gel composition in both network series. The synthesized networks formed a dense surface layer as the temperature increased past the gel collapse point. This dense layer retarded water efflux and thereby resulted in water pockets at the membrane surface.

Acrylamides↗

A novel synthetic vitamin D3 analogue, 2-beta-(3-hydroxypropoxy)-calcitriol (ED-71): its biological activities and pharmacological effects on calcium metabolism.

A novel vitamin D3 analogue, [2 beta-(3-hydroxypropoxy)-calcitriol: ED-71] showed a similar Ca-regulating activity as calcitriol in the in vivo and in vitro Ca mobilization test and ex vivo intestinal Ca absorption assay using vitamin D-deficient rats. The differentiation-inducing activity of ED-71 in mouse myeloid leukemia cell line (WEHI-3 cell) was slightly less than that of calcitriol. ED-71 distributes predominantly in plasma as an intact form and its half-life plasma was twice as long as that of calcitriol. Further study revealed that the higher binding potency of ED-71 to plasma-specific vitamin D-binding protein (DBP) compared with that of calcitriol accounts for its stability in the blood circulation. The pharmacological effect of ED-71 for the animal models with osteoporosis seemed to be better than that calcitriol. These results suggest that ED-71 should become a valuable therapeutic long-acting drug for patients with osteoporosis.

Animals↗