Biomedical subjects

Y Takezawa

Publications and source records attributed to Y Takezawa.

At least 55 records · Page 3Linked to original sources

PubMed1993

Ultrasonic diagnosis of 3,2'-dimethyl-4-aminobiphenyl induced tumors in the urogenital organs of F344 rats.

The usefulness of transabdominal ultrasonography in the diagnosis of 3,2'-dimethyl-4-aminobiphenyl- and testosterone propionate-induced tumors of the urogenital organs was evaluated in F344 rats. Seven mass lesions (1 ventral prostate, 1 dorsolateral prostate, 3 seminal vesicles, and 1 kidney) in the urogenital organs could easily be diagnosed concerning size and localization by ultrasound. Histological examination revealed a lesion in the ventral prostate to be an abscess and the other tumors to be malignant. Three hydronephroses by tumor invasion to the ureter, and six tumors in organs other than the urogenital organs could be detected by ultrasound. The threshold of malignant tumor detection by ultrasound was 7 mm in actual length. The size of the mass lesion estimated by ultrasound correlated well with the direct measurement (r = 0.96). Transabdominal ultrasonography is useful for diagnosing the localization of experimental tumors and accurately measuring their size in the urogenital organs of rats.

Adenocarcinoma↗

PubMed1993

[Measurement of serum PSA by DELFIA PSA kit and its application for mass screening. The Gunma Urological Oncology Study Group].

The significance of prostate specific antigen (PSA) measured by DELFIA PSA kit in the 1,177 serum samples examined by mass screening for prostate cancer was evaluated. All subjects were examined by questionnaire, digital rectal examination (DRE) and prostatic acid phosphatase (PAP) and the subjects in whom prostate cancer was suspected from abnormal DRE and/or elevated PAP were recommended to receive the secondary screening for the presence of prostate cancer. All serum specimens used for this study were kept in our serum bank. The cut-off value was investigated between non-cancer subjects (diagnosed as normal, voiding disturbance or BPH) and prostate cancer patients. When the cut-off value was 2.89 ng/ml, the sensitivity, specificity and accuracy as prostate marker was 80.6%, 90.0% and 89.4%, respectively. Therefore, the cut-off value was determined as 3.0 ng/ml. The significance of PSA was retrospectively evaluated compared to PAP in the subjects examined by our mass screening. Twenty eight of the 39 palpable prostate cancers which could not be detected from the PAP level were detected from the PSA level, namely the sensitivity of the detection using the PSA level is more excellent than that using PAP. However, the false negative rate obtained using PSA was high (30.3%) in the patients with stage B disease. The relationship among serum PSA concentration, prostate size estimated by DRE and age was investigated. PSA was increased with age and prostate size. This estimation should be confirmed by using an ultrasonography because the prostate size obtained by DRE is inaccurate as compared with that obtained by ultrasonography.

Adult↗

PubMed1993

[Clinical evaluation of Augpenin (clavulanic acid-ticarcillin) in urinary tract infections: especially against beta-lactamase producing strains].

Augpenin contains ticarcillin (TIPC) and clavulanic acid (CVA), at a ratio of 15:1. The beta-lactamase inhibitor, CVA, has been added to protect the TIPC from inactivation by beta-lactamase. To investigate the drug efficacy and safety against urinary tract infections (UTI), Augpenin was administered to 33 patients with chronic complicated UTI and 7 patients with acute pyelonephritis. Thirty two cases were evaluable by the UTI criteria. Excellent results were obtained in 6 of the cases of acute pyelonephritis, and moderate results in 1 case, with an overall effectiveness rate of 100%. Excellent results were obtained in 14 of the cases of chronic complicated UTI, moderate results in 9 cases, and poor results in 2 cases, with an overall effectiveness rate of 92%. No adverse reactions were noted, but a transient elevation of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase levels was observed in 2 cases.

Adolescent↗

PubMed1992

Small-angle synchrotron x-ray scattering reveals distinct shape changes of the myosin head during hydrolysis of ATP.

In the energy transduction of muscle contraction, it is important to know the nature and extent of conformational changes of the head portion of the myosin molecules. In the presence of magnesium adenosine triphosphate (MgATP), fairly large conformational changes of the myosin head [subfragment-1 (S1)] in solution were observed by small-angle x-ray scattering with the use of synchrotron radiation as an intense and stable x-ray source. The presence of MgATP reduced the radius of gyration of the molecule by about 3 angstrom units and the maximum chord length by about 10 angstroms, showing that the shape of S1 becomes more compact or round during hydrolysis of MgATP. Comparison with various nucleotide-bound S1 complexes that correspond to the known intermediate states during ATP hydrolysis indicates that the shape of S1 in a key intermediate state, S1-bound adenosine diphosphate (ADP) and phosphate [S1**.ADP.P(i)], differs significantly from the shape in the other intermediate states of the S1 adenosine triphosphatase cycle as well as that of nucleotide-free S1.

Adenosine Triphosphate↗

PubMed1992

Inhibition of 3 alpha-hydroxysteroid oxidoreductase and 5 alpha-reductase activity by antiandrogens and indomethacin in the rat prostate.

We studied the effects of antiandrogens in vitro on inhibition of 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) and 5 alpha-reductase activities in the rat prostate. Kinetic and inhibition experiments were analyzed by thin layer chromatography. Cyproterone acetate (CA), chlormadinone acetate (CMA), and TZP-4238 (TZP), which is more potent than other antiandrogens, were used as inhibitors and were compared with indomethacin IND, which is a recognized 3 alpha-HSOR inhibitor. The IC50S of CA, CMA, IND, and TZP for 3 alpha-HSOR reductase in cytosol were about 5, 10, 10, and 100 microM, respectively, and inhibition was competitive. The IC50 of IND for 3 alpha-HSOR reductase in microsomes was 20 microM. The IC50S of other inhibitors were > 100 microM, and inhibition was noncompetitive. The IC50S of CA, CMA, IND, and TZP for 3 alpha-HSOR oxidase in cytosol were > 100 microM, and inhibition was competitive or noncompetitive. Inhibition of 3 alpha-HSOR oxidation was not observed in microsomes. The difference between these inhibition patterns suggests that there may be 4 isoenzymes in rat prostatic tissue. The IC50S of MK-906, CMA, and TZP for 5 alpha-reductase in prostate homogenate were about 0.01, 200, and 200 microM, respectively.

3-Hydroxysteroid Dehydrogenases↗

PubMed1992

Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia.

The effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One- to 2-year-old beagle dogs were castrated and administered 75 mg/week of androstanediol (A-diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP-4238, 0.1 mg/kg/day of TZP-4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A-diol plus E2. Treatment with 0.5 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP-4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/kg/day of TZP-4238 decreased 5 alpha-reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP-4238 and CMA were effective in inhibiting the growth of hormone-induced canine BPH, and TZP-4238 was at least 5 times more potent than CMA. TZP-4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen-AR complex. TZP-4238 decreased 5 alpha-reductase activity by prevention of the androgen action described above.

Androstane-3,17-diol↗

PubMed1992

Inhibitory influence of a new steroidal anti-androgen, TZP-4238, on prostatic hyperplasia in the beagle dog.

The effect of a synthetic steroidal anti-androgen, TZP-4238, on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Old male beagle dogs (5-9 years old) were divided into three experimental groups. Group 1 consisted of BPH controls. Groups 2 and 3 received TZP-4238 0.1 mg/kg/day and chlormadinone acetate (CMA) 0.3 mg/kg/day p.o., respectively, for 5 months. In group 1, glandular hyperplasia of the prostate was clearly detected. In contrast, TZP-4238 (Group 2) or CMA (Group 3) produced marked atrophy of the glandular epithelium. In addition, a histopathological study showed that TZP-4238 or CMA medication for 5 months exerted no effect on the testes and the pituitary luteinizing hormone (LH) cells. Therefore, it is suggested that TZP-4238 (0.1 mg/kg) or CMA (0.3 mg/kg) causes regression of spontaneous canine BPH without any histopathological effects on the testes and pituitary LH cells. However, slightly decreased serum testosterone levels were found in TZP-4238-treated animals, due apparently to a direct and/or indirect effect on the testes. Thus, it is suggested that a marginal antigonadotrophic effect cannot be excluded. It is concluded that TZP-4238 is a potent anti-androgen for the treatment of spontaneous canine BPH, without any negative influence on the function of the testes and the pituitary LH cells.

Animals↗

PubMed1992

[Endocrine environment of benign prostatic hyperplasia--relationships of sex steroid hormone levels with age and the size of the prostate].

To determine the influence of endocrine factors on benign prostatic hyperplasia (BHP), the levels of three sex steroid hormones i.e., total testosterone (Total-T), free testosterone (Free-T) and estradiol (E2), were measured in serum of healthy 154 men. Their ages ranged from 18 to 91 years old. In 59 men, prostatic size was estimated by digital examination and was subdivided into three groups: smaller than or equal to walnut size, small hen's egg size and equal to or larger than hen's egg size. Firstly, relationships of sex hormone levels with age were studied. There was a slight decrease in Total-T over 60 years old, a significant decrease in Free-T, and no change in E2 with age. Thus, E2/Total-T and E2/Free-T ratio increased significantly after middle-age. Secondly, relationships of hormone levels with prostatic size were studied. In the larger prostate group, a significantly lower level of Total-T and significantly higher level of E2 were detected. But there was no difference in Free-T. Thus, the prostatic size was correlated positively with E2 level, E2/Total-T and E2/Free-T ratio. These suggest that the endocrine environment tended to be estrogens-dominant with age, in particular, after middle-age, and that patients with large prostates have more estrogens-dominant environments. We conclude that estrogens are key hormones for the induction and the development of BPH.

Adolescent↗

PubMed1992

[Clinical effect of Cernilton in chronic prostatitis].

Twenty-five patients with chronic prostatitis were given Cernilton tablets. Improvement of subjective symptoms and objective findings was noted in 96.0% and 76.0% of the cases. Sonographic findings in the prostate showed 33-100% improvement in four objective items. No side effects were observed in any case after Cernilton medication. Cernilton was judged to be an effective drug for chronic prostatitis.

Administration, Oral↗

PubMed1991

[Estrogen formation in the central nervous system and characteristics of aromatase of rat hypothalamus].

Estrogen formation from androst-4-ene-3,17-dione and its kinetics were studied using microsomes from rat hypothalamus. [4-14C] androst-4-ene-3,17-dione and a homogenate of rat hypothalamus were incubated in the presence of NADPH at 37 degrees C for 3 hrs. The estrogen fraction was extracted from the incubation mixture with ethyl acetate, purified by column chromatography on Sephadex LH-20 and Bond Elut C18, and separated into estrone and estradiol fractions by HPLC. In analysis of the trimethylsilyl (TMS) derivatives of each fraction by gas chromatography-mass spectrometry (GC-MS), the molecular ion peak of the estrone fraction appeared at m/z 344, within 2 amu of that for the TMS derivative of natural estrone. The retention time of the estrone fraction derivative was 11.6 min, the same as that of natural estrone. 14C-estrone was thus concluded to be biosynthesized from [4-14C]-androst-4-ene-3,17-dione in rat hypothalamus. The kinetics of the aromatase of rat hypothalamic tissue was studied by measuring 3H2O released from [1 beta-3H]-androst-4-ene-3,17-dione and estrone as the estrogen product by measured gas chromatography selected ion monitoring (GC-SIM). High correlation was found between 3H2O release and estrone measured by GC-SIM (r = 0.97). Aromatase activity was linear with respect to incubation time and quantity of tissue. Km and Vmax were 30.3 nM and 7.98 fmol estrogen/h/mg of wet tissue, respectively. 4-hydroxyandrostenedione (4-OH-A) suppressed the activity of aromatase in both rat hypothalamic and human placental tissue in a concentration-dependent manner. Polyclonal IgG to human placental aromatase also suppressed aromatase activity of human placental tissue, but only slightly suppressed that of rat hypothalamus. The molecular structure of aromatase in rat hypothalamus was thus concluded to differ from that in human placenta.

Androstenedione↗

PubMed1991

Sectional anatomy of the pelvis in the male rat with ultrasound correlations.

Ten-week-old male Wistar rats were used for sectional anatomy and ultrasonic diagnosis of the pelvis. The prostate and the urinary bladder were identified easily on longitudinal section by ultrasound examination. The prostate (ventral, lateral, and dorsal lobes) was located in the midline of the pelvis cavity on transverse sections and the caudal side of the urinary bladder on longitudinal sections. The urinary bladder was positioned at the cranial side of the prostate on longitudinal sections and in the midline of the pelvis cavity on transverse sections. The seminal vesicles were located at right and left positions of the urinary bladder. Ultrasonic diagnosis was estimated to be useful for experimental studies and we hope that ultrasound techniques may reduce the number of rats used for the treatment of prostate and urinary bladder cancers.

Animals↗

PubMed1990

A case of adenocarcinoma of the renal pelvis.

A 28-year-old female had adenocarcinoma arising from the renal pelvis with ascites containing adenocarcinoma cells. The primary site was treated with radical nephrectomy, resection of the remnant ureter with a bladder cuff. Combination chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (CAP) was performed as an adjuvant therapy. Approximately 3 years after the nephrectomy, she is currently alive with no clinical evidence of recurrence. CAP seems to have been effective in the treatment of the disease.

Adenocarcinoma↗

PubMed1989

Osteonectin inhibiting de novo formation of apatite in the presence of collagen.

The effect of bone matrix protein of osteonectin on de novo formation of apatite was studied in a wide range of calcium phosphate solutions in the presence of collagen. In every solution, from which amorphous calcium phosphate, octacalcium phosphate, or apatite precipitated as a possible initial phase, osteonectin at concentrations less than 1 microM retarded the precipitation, subsequent transformation to apatite, and ripening crystal growth of apatite. Collagen present as either reconstituted or denatured form had no effect on the osteonectin-associated reactions as well as osteonectin-free reactions, and no structural correlation was observed between collagen fibrils and any of the calcium phosphates that appeared in our system. Direct measurement of free calcium levels in the solutions suggested that the reduction in calcium activity due to complexing with osteonectin hardly explained the inhibitory activity of osteonectin in retarding the formation of apatite. Instead, our transmission electron microscopic (TEM) observation strongly suggested that the primary mechanism for osteonectin to inhibit the formation of apatite is to block growth sites of calcium phosphates nucleated. The apatite thus formed in the presence of osteonectin showed less resolved X-ray diffraction patterns, partly because of smaller crystallites as suggested by TEM.

Animals↗

PubMed1989

[Self-setting apatite cement. 6. Possibility as bone substitute].

Self-setting apatite cement was investigated to evaluate its use as a possible bone substitute in the rat femur. The implant sites were recovered at intervals up 12 weeks postoperatively and investigated by the use of x-ray diffraction, contact microradiography, light and electron microscopy. By x-ray diffraction analysis, the cement placed for at least one day in the medullary canal of rats was found to be completely converted to a set phase of hydroxyapatite resembling the main inorganic phase of bone. In any specimens prepared at 1, 4, 12 weeks after implantation, no appreciable foreign body response was observed in the tissue around the set cement. At four weeks after implantation the set cement was in tight contact with the newly formed bone which appeared to involve osteocytes in lacunae and osteoblastic cells on its surface. At twelve weeks after implantation, the newly formed bone tended to grow into the interior of the set cement. With scanning electron microscopy, the newly formed bone was found to be directly deposited on the set cement. The newly formed bone consisted of fine needle-like crystals. These results strongly suggest that this cement is well tolerated by bone tissue and osteogenesis when used as a bone substitute. The advantage of the present material as a promising bone substitute is that it can be filled in surgical or traumatic bone defect as a slurry or paste.

Animals↗

PubMed1989

[Self-setting apatite cement. 8. Dissolution and remineralization behavior of 45Ca-apatite cement].

Self-setting apatite cement hardens into a mass of single phase apatite when mixed with diluted phosphoric acid. Structurally this mass consists of two types of apatite, i.e. the seed apatite used as a setting accelerator and the matrix apatite formed afterward in the reaction of dicalcium phosphate dihydrate (DCPD) and tetracalcium phosphate (Te-CP). To investigate the dissolution behavior of self-setting apatite cement in detail, two types of 45Ca labeled apatite cement were prepared. In one, the seed apatite was labeled with 45Ca (45Ca-HAp cement) and in the other the matrix apatite was labeled with 45Ca through use of 45Ca-DCPD (45Ca-DCPD cement). Solubility, estimated from the concentration of 45Ca released in 1 mM of organic acid (e.q. acetic, lactic, or citric acid) with initial pH adjusted to 4.0 at 37 degrees C, was approximately zero for 45Ca-HAp cement, whereas the solubility of 45Ca-DCPD cement was approximately the same as unlabeled cements used so far. This finding suggests that dissolution of the matrix apatite governs dissolution of the set cement, though comparison of X-ray diffraction patterns and electron micrographs of the seed apatite and apatite in the set cement showed no essential difference in crystallinity and crystal shape. The fact that the matrix apatite was formed by enveloping the seed apatite may account for the preferential dissolution of matrix apatite. In synthetic saliva labeled with 45Ca having a degree of supersaturation with respect to apatite comparable to rest saliva, 45Ca concentration in solution decreased once the cement pellet was introduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Apatites↗

PubMed1989

[Self-setting apatite cement. VII. Barium-apatite as radio-opaque medium].

Addition of barium hydroxyapatite (BaAp) successfully bestowed clinically acceptable radioopacity to the self-setting apatite cement consisting of an equimolar mixture of tetracalcium phosphate and dicalcium phosphate dihydrate. To accelerate the setting reaction which was retarded by Ba2+ released from BaAp at a lower pH during first stage of spatulation with 20 mM phosphoric acid, calcium hydroxyapatite (CaAp) was added to the cement mixture. At about 20 wt% of BaAp and 20 wt% CaAp, the setting reaction proceeded at a neutral or weak alkaline pH, which is one of the most promising aspects of the self-setting cement and assures that this type of cement may be the least irritating of the dental cements presently available. The cement spatulated at L/P = 0.4 set within 10 minutes and its radiopacity was comparable to or more than that of tooth enamel. The wet compressive strength of the set cement stored for one day in synthetic saliva at 37 degrees C was approximately 100 kgf/cm2. Although this value is almost one fourth that of 40 wt% CaAp cement, this cement appears to be strong enough to apply as root canal filling material.

Barium↗

PubMed1989

[Studies on physico-chemical properties of self-setting apatite cement].

A new dental cement was developed by use of tetracalcium phosphate monoxide (Te-CP) and dicalcium phosphate dihydrate (DCPD). When an equimolar mixture of the two calcium phosphates was mixed with diluted phosphoric acid, it hardened into a phase of hydroxyapatite (HAp) resembling the main inorganic phase of hard tissues. The present study was undertaken to investigate physico-chemical properties of this newly developed apatite cement and to evaluate its potential as dental cement to clinical application. The setting time was reduced in the presence of synthetic HAp, indicating added HAp to be an accelerator in the setting reaction. The pH of paste rapidly increased to a neutral range from initial solution acidity of about 2.0 and the subsequent setting reaction proceeded in a neutral and weak alkaline pH range. The hardened solid 4 hours after saturation was identified as single phase of apatite by X-ray diffraction. The HAp crystallinity of the set cement varied with the crystallinity of HAp added as setting accelerator. The wet compressive strength of the cement stored for one day in synthetic saliva at 37 degrees C increased to 400 kg/cm2 as added HAp crystallinity decreased. Moreover no disintegration took place when the cement was stored at 37 degrees C in synthetic saliva, which was undersaturated with respect to DCPD but well supersaturated for HAp. In clinical application to animals, no significant cleavage was observed between the hard tissues and the cement by SEM even three months after the cement paste was filled in the tooth cavity of monkeys. In the specimen prepared one week after implantation in the medullary canal of rats, no inflammatory cell appeared. The specimen prepared one month after implantation showed that the set cement was tightly contacted with newly formed bone. These findings strongly suggest that the newly developed self-setting apatite cement is useful as a pulp capping agents, root canal fillings and bone substitute.

Animals↗

PubMed1989

Effect of intravesical instillation of antitumor drugs in the development of N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tumors in rats.

We examined the effects of intravesical instillation of adriamycin (ADM) and cis-diammine-dichloroplatinum (CDDP) on the development of bladder tumors induced by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in 115 rats. Intravesical instillation was performed in two ways; continuous administration (5 times a week for 5 weeks) and intermittent administration (once a week). Group 1 (control group) did not receive intravesical instillation. Group 2 I(ADM), group 3 (CDDP) and group 4 (physiological saline) were continuous type. Group 5 (ADM), group 6 (CDDP) and group 7 (physiological saline) received intermittent administration. Bladder weight was significantly higher in group 4 than in groups 1 or 7, and that in groups 2 and 3 than that in group 5 and 6. In groups 2, 3, 5 and 6 bladder weight was almost normal or higher than in the control group, and in group 3 histologically cancer was not seen in one rat. Physiological saline had promoting activity, and ADM and CDDP had both inhibitory and promoting activities. Also, intravesical instillation itself was suggested to promote tumor development under carcinogenic circumstances. We conclude that intermittent intravesical instillation should be performed to inhibit tumor recurrence and intravesical instillation therapy should not be performed clinically for a long period.

Administration, Intravesical↗