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Biomedical subjects

Y Takezawa

Publications and source records attributed to Y Takezawa.

At least 37 records · Page 2Linked to original sources

[Tissue polypeptide antigen as a biological marker of malignant pleural mesothelioma].

To evaluate the role of tissue polypeptide antigen (TPA) as a biological marker of malignant pleural mesothelioma (MPM), we used immunohistochemical techniques to detect TPA in tumor cells, and we measured the content of TPA in serum from patients with MPM. In 14 of 16 patients with MPM, TPA was detected in the cytoplasm of tumor cells. Epithelial-type cells from 11 of 12 patients were stained positively (91.7%), and sarcomatous-type cells from 7 of 8 patients were stained positively (87.5%). Serum TPA levels were abnormally high in 7 of 9 patients. Two of three patients with stage-I disease had normal serum TPA levels, and all patients whose disease was at stage II or higher had abnormal serum TPA levels. Serum TPA levels increased as MPM progressed. These results suggest that the serum TPA level can be used as a biological marker of MPM.

Adult↗

Small-Angle X-ray Diffraction of Muscle Using Undulator Radiation from the Tristan Main Ring at KEK.

Time-resolved X-ray diffraction of muscle has demanded ever-increasing flux into small sample volumes with low beam divergence. Results are reported of static and time-resolved small-angle X-ray diffraction studies on muscle fibers using a hard X-ray undulator installed in the Tristan main ring at KEK, Tsukuba, Japan, as an innovative source of synchrotron radiation more intense and better collimated than that available with the Photon Factory bending-magnet beamline. Static studies used the low divergence of the source to obtain detailed high-quality diffraction patterns of stable muscle states. The diffraction patterns from live skeletal muscles showed the numerous (over 100) meridional reflections. The well collimated beam from the undulator made it possible to clearly resolve, with an angular resolution of ca 700 nm, the closely spaced diffraction peaks arising from the two halves of the thick filaments centred on the M lines in a sarcomere, in addition, the diffraction peaks from the thin filaments on opposite sides of the Z bands could be resolved with an angular resolution of ca 1000 nm. The detailed structure of the meridional pattern defines the nature of the molecular packing in the thick and thin filaments. Time-resolved experiments using a focusing mirror aimed to prove cross-bridge states in striated muscle fibers by collecting X-ray diffraction data at a 0.185 ms time resolution from sinusoidally oscillating chemically skinned rabbit muscle fibers during active contraction and in rigor. When sinusoidal length changes at 500 Hz with a peak-to-peak amplitude of 0.6% of the muscle length were applied to a small fiber bundle, the tension showed a simple elastic response during the length oscillation. In the active muscle the intensity of the 14.5 nm myosin-based meridional reflection changed out of phase with the tension change during the oscillating length change. In contrast, in the rigor muscle it occurred in phase with the tension change. The high time-resolved experiments provide an insight into the coupling between conformational changes and force generation of the actomyosin cross-bridges. These studies provide a preview of the expected gains for muscle studies from the more widespread use of undulator radiation at third-generation synchrotron sources.

Journal Article↗

Acute renal failure in a patient with chronic glomerulonephritis after the administration of luteinizing hormone-releasing hormone analogue given for rectal obstruction due to prostate cancer.

We report a case in which rectal obstruction due to prostate cancer was exacerbated due to an ileus after the administration of luteinizing hormone-releasing hormone analogue. The obstruction to led to copious vomiting, dehydration and renal failure which necessitated hemodialysis. Improvement of the patient was noted four weeks after the start of hormonal treatment with a decrease in rectal obstruction concomitant with decreases in testosterone and prostate specific antigen levels.

Acute Kidney Injury↗

[The effects of antiandrogen TZP-4238 on plasma testosterone and LH and steroidogenesis in rat and canine testis].

TZP-4238 suppresses plasma testosterone in humans, but its action on the androgen biosynthesis pathway has not been established. Therefore, we researched the testicular testosterone level and the testosterone biosynthesis pathway in vitro in rats before and after receiving a single or continuous oral dose of TZP-4238. The total testosterone fell to 60% of the basal level within 3-8 hr (p < 0.05) and then returned to the control concentration by 24 hr after a single administration of 32 mg/kg. The alteration of the plasma testosterone level correlated well with that of the intratesticular level, which was decreased to 50% at 3-8 hr and recovered to the control level by 24 hr. However, the decrement of the plasma LH level at 3-8 hr after a single oral administration was slight and it then returned to the original level at 12 hr. During the 8 weeks of daily administration of 0.5 mg/kg of TZP-4238 or chlormadinone acetate to dogs, the plasma testosterone levels were slightly lower than the basal extent. In vitro experiments were conducted on the rat testis using the exogenous precursor steroids 20 alpha-hydroxycholesterol, pregnenolone and progesterone, in various steps leading to the biosynthesis of testosterone. Trilostane acted at 3 beta-hydroxysteroid dehydrogenase (50% inhibition concentration, IC50 was 1 microM), ketoconazole inhibited the 17 alpha-hydroxylase, and C20, 22- and C17, 20-lyase activities, with an IC50 of 1-50 microM. Cyproterone acetate inhibited both the 3 beta-hydroxysteroid dehydrogenase (IC50;50 microM) and C17, 20-lyase. On the other hand, TZP-4238 exhibited a weaker inhibition of 3 beta-hydroxysteroid dehydrogenase (IC50; 100 microM) than cyproterone acetate, but not of hydroxylase and lyase. Though TZP-4238 did not inhibit the increased testosterone level induced by hCG, trilostane markedly inhibited the effect induced by hCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effects of a new steroidal antiandrogen, TZP-4238 (17 alpha-acetoxy-6-chloro-2-oxa-4, 6-pregnadiene-3, 20-dione), on spontaneously developed canine benign prostatic hyperplasia.

The effects of the new steroidal antiandrogen, TZP-4238 on spontaneously-developed canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used for the treatment of BPH and prostatic cancer in Japan. Aged beagle dogs (5-9 years old) with spontaneously developed BPH (mean prostate volume, 17.7ml) were treated orally with a placebo, TZP-4238 (0.1 mg/kg/day, 0.01 mg/kg/day), or CMA (3 mg/kg/day), for 25 weeks. Prostate volume was measured by transrectal ultrasonography before treatment and every 5 weeks during treatment. TZP-4238 produced a regression in spontaneously developed canine BPH, its effects being more potent than those of CMA. TZP-4238 reduced the content of testosterone, dihydrotestosterone (DHT) and androgen receptor in the prostates of these animals, suggesting antiandrogenic mechanisms of the agent. TZP-4238 also appeared to reduce 5 alpha-reductase activity by prevention of the androgen action in prostate as described above.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

[Clear cell sarcoma extending into the inferior vena cava].

A 6-year-old boy who had been diagnosed as having Wilms tumor at the prior hospital was admitted to our hospital for investigation of a right flank mass and macrohematuria in October 1990. Magnetic resonance imaging showed Wilms tumor of the right kidney extending into the inferior vena cava. Right radical nephrectomy, lymphadenectomy and thrombectomy were done on October 30th, 1990. Pathological findings indicated clear cell sarcoma of the kidney. One week after the operation, radiotherapy and chemotherapy with actinomycin D (ACTD), vincristine sulfate (VCR), doxorubicin hydrochloride (DXR) and cyclophosphamide (CPM)) were started according to the protocol by National Wilms Tumor Study (NWTS) III. However, he died of bone metastases and pneumomycosis on October 13th, 1992. Clear cell sarcoma of the kidney (CCSK) is a rare tumor accounting for about 4-5% of Wilms tumors. This is the first report on CCSK with tumor thrombus in Japan.

Child↗

[Clinical analysis of ureteral injuries].

Six cases of ureteral injuries were analyzed. Two cases were male and 4 cases were female. The right side was affected in 1 case and the left in 5 cases. The affected portion was the uretero-pelvic junction in 1 case and lower iliac vessels in the other cases. Five cases were iatrogenic injuries in surgical or gynecological pelvic operation, and the other was due to blunt trauma. Intraoperative diagnosis was made in 4 cases. Drain leakage led to diagnosis in one case and pyelonephritis in another. Ureteroureterostomy was performed in 2 cases, pyeloureterostomy in 1 case, ureteroneocystostomy with psoas hitch in 1 case, Boari bladder flap in 1 case and simple suture in 1 case. 4-0 or 5-0 Dexon with an atraumatic needle was used for all anastomoses. Except for case 1, who died of the recurrence of carcinosarcoma, renal functions were preserved in all patients during the follow-up period ranging from 5 months to 7 years 8 months.

Adult↗

Conformational changes of the myosin heads during hydrolysis of ATP as analyzed by x-ray solution scattering.

We have shown for the first time that the myosin head (subfragment-1, S1), the energy-transducing component in the actomyosin motor system undergoes a distinct shape change during hydrolysis of ATP using x-ray solution scattering techniques. Among various analogs for intermediate states of the S1 ATPase cycle, the complexes with MgADP and vanadate (S1.ADP.Vi), MgADP and beryllium fluoride (S1.ADP.BeF3), or MgADP and aluminum fluoride (S1.ADP.AIF4) showed a shape change similar to that in the presence of MgATP, but the complexes with ATP gamma S (S1.ADP gamma S) and MgADP trapped by cross-linking with pPDM (S1.ADP-pPDM) seemed to have a shape similar to that of nucleotide-free S1. These results indicate that the shape of an S1**.ADP.Pi state is more rounded or bent than in other intermediate states of the S1 ATPase cycle. Such changes occur in light chain 2-deficient S1 and also in smooth muscle S1. However, MgADP-fluoride complexes with smooth muscle S1 (without phosphorylation of a regulatory light chain) seemed to have a structure similar to that of nucleotide-free S1. Analysis of x-ray scattering data indicated that a conformational change of S1 in the presence of MgATP might be caused by a hinge-like bending movement between the catalytic and regulatory domains. The global change of S1 is correlated with some specific changes of a nucleotide-binding moiety.

Adenosine Diphosphate↗

[Effects of antiandrogen TZP-4238 on the prostatic androgen receptor and prostatic androgen in rat].

TZP-4238, a new steroidal antiandrogen, is an orally active drug in rats and dogs. The effects of TZP-4238 on the androgen receptor and androgen content were examined in comparison with other antiandrogens in rats. The prostate DHT levels decreased markedly within 4-8 hr after a single oral administration of TZP-4238 8mg/kg. The prostatic testosterone concentrations fell below the detection limit (5pg/g of tissue) at 4-12 hr after the initiation of treatment. The plasma testosterone level also fell to 60% of the control level after 4-8 hr and then returned to the normal range. Eight percent of DHT present in normal prostatic tissue was located in the nuclear fraction. TZP-4238 reduced the concentration of DHT in nuclei to 50% of the normal level. The concentration of the plasma drug which induced a 50% decrease in the prostatic DHT, the IC50, was about 10ng/ml, while the IC50 value for plasma testosterone was 30-50ng/ml. After oral administration of 15-OH TZP-4238, the main metabolite, the level of plasma testosterone was significantly elevated above the control level. The androgen receptor level was markedly reduced at 24 hr following castration and returned to the normal range within 5 hr of a single injection of testosterone. TZP-4238 reduced the nuclear androgen receptor level to 60% at 24 hr after a single oral dose and then, the receptor content returned to its original level. Both 15-OH TZP-4238 and cyproterone acetate also reduced the androgen receptor and DHT contents to 50%. A series of in vivo studies demonstrated that TZP-4238 inhibited the uptake of testosterone and the decrease of DHT and testosterone, and decreased the nuclear androgen receptor in the rat prostate.

Androgen Antagonists↗

Synergistic effects of estrogen with androgen on the prostate--effects of estrogen on the prostate of androgen-administered rats and 5-alpha-reductase activity.

To clarify the effects of estrogen on the prostate of androgen-treated rats, we administered estradiol (E2; 0.01 mg/day) to testosterone (T; 1 mg/day)-treated Wistar rats under various conditions. There were three variable factors: the age of the rat, the untreated period after castration, and the presence of testes. Under all conditions, E2 stimulated the growth of the prostate in T-treated rats compared with growth in rats in treated with T only. To analyze the mechanism underlying this enhancement of prostate growth by estrogen, we measured 5-alpha-reductase activity and calculated its kinetic parameters, i.e., both Vmax and Km. The Vmax of the nuclear fraction was higher in E2-administered T-treated rats than in T only-treated rats. In contrast, the Vmax of the microsomal fraction was lower in E2-administered rats. Km values in the two groups showed no significant differences. Elevation of the nuclear fraction of 5-alpha-reductase activity could explain the synergistic effects of estrogen on the prostate growth of androgen-treated rats.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

X-ray diffraction evidence for the extensibility of actin and myosin filaments during muscle contraction.

To clarify the extensibility of thin actin and thick myosin filaments in muscle, we examined the spacings of actin and myosin filament-based reflections in x-ray diffraction patterns at high resolution during isometric contraction of frog skeletal muscles and steady lengthening of the active muscles using synchrotron radiation as an intense x-ray source and a storage phosphor plate as a high sensitivity, high resolution area detector. Spacing of the actin meridional reflection at approximately 1/2.7 nm-1, which corresponds to the axial rise per actin subunit in the thin filament, increased about 0.25% during isometric contraction of muscles at full overlap length of thick and thin filaments. The changes in muscles stretched to approximately half overlap of the filaments, when they were scaled linearly up to the full isometric tension, gave an increase of approximately 0.3%. Conversely, the spacing decreased by approximately 0.1% upon activation of muscles at nonoverlap length. Slow stretching of a contracting muscle increased tension and increased this spacing over the isometric contraction value. Scaled up to a 100% tension increase, this corresponds to a approximately 0.26% additional change, consistent with that of the initial isometric contraction. Taken together, the extensibility of the actin filament amounts to 3-4 nm of elongation when a muscle switches from relaxation to maximum isometric contraction. Axial spacings of the layer-line reflections at approximately 1/5.1 nm-1 and approximately 1/5.9 nm-1 corresponding to the pitches of the right- and left-handed genetic helices of the actin filament, showed similar changes to that of the meridional reflection during isometric contraction of muscles at full overlap. The spacing changes of these reflections, which also depend on the mechanical load on the muscle, indicate that elongation is accompanied by slight changes of the actin helical structure possibly because of the axial force exerted by the actomyosin cross-bridges. Additional small spacing changes of the myosin meridional reflections during length changes applied to contracting muscles represented an increase of approximately 0.26% (scaled up to a 100% tension increase) in the myosin periodicity, suggesting that such spacing changes correspond to a tension-related extension of the myosin filaments. Elongation of the myosin filament backbone amounts to approximately 2.1 nm per half sarcomere. The results indicate that a large part (approximately 70%) of the sarcomere compliance of an active muscle is caused by the extensibility of the actin and myosin filaments; 42% of the compliance resides in the actin filaments, and 27% of it is in the myosin filaments.

Actins↗

[Concentrations of new quinolone agents in serum and prostate tissue].

Twenty five patients with benign prostate hypertrophy were administered ofloxacin (OFLX) simultaneously with norfloxacin (NFLX) in 6 patients, ciprofloxacin (CPFX) in 10, tosfloxacin (TFLX) in 5 and enoxacin (ENX) in 4 patients. The dose of these new quinolones was 100 mg (except 150 mg of TFLX). Their concentrations in the serum and the prostate tissue were measured by high performance liquid chromatography (HPLC). The serum concentration of OFLX was significantly higher than that of NFLX, CPFX, TFLX or ENX. The prostate tissue concentration of OFLX was significantly higher than that of CPFX or TFLX. The ratio of tissue versus serum concentration of each new quinolone agent was not significantly different. The high OFLX tissue concentration appeared to be caused by the high serum concentration.

4-Quinolones↗

[Clinical analysis of methicillin-resistant Staphylococcus aureus (MRSA) infection].

In 14 patients from which methicillin-resistant Staphylococcus aureus (MRSA) was isolated at the Department of Urology, Tone Chuo Hospital June, 1992 and October, 1993, the site of infection, background of patients, and drug resistance were analyzed. The 14 patients consisted of 11 males and 3 females between 45 and 85 years old with a mean of 71.6 years. The site from which MRSA was isolated was urine in 11, wound in 2, nasal cavity in 1, pharynx in 1, and renal fistula in 1 (detected at 2 or more sites in 2). The underlying condition was prostate hyperplasia in 2, prostate cancer in 4 (after radical prostatectomy in 1, complicated by bladder stone in 1), bladder tumor in 3, (during bladder instillation of BCG in 1), perirenal abscess in 2, renal pelvic tumor in 1, neurogenic bladder in 1, and after Boari's operation in 1. Urethral catheterization had been performed in 3. A fewer of 38 degrees C or above was noted in 3. Mixed infection was observed in 10, and was caused by Escherichia coli in 2, Proteus mirabiris in 1, Candida in 1, Klebsiella in 2, Pseudomonas aeruginosa in 2, and Serratia in 2. Four patients has previously been administered antibiotics, which were third generation cephems in 3 and penicillin in 1. The drug sensitivity was 100% for vancomycin (VCM), 30% for imipenam (IMP), 31% for minomycin (MINO), 31% for amikacin (AMK), and 7% for fosfomycin (FOM). As for chemotherapy, VCM+FOM+sulbactam/cefoperazone were administered to 6, and ceftazidime+ MINO were administered to 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Lupus cystitis. report of a case.

A 42-year-old female with a history of systemic lupus erythematosus (SLE) visited the Department of Internal Medicine at our hospital complaining of anorexia. Hydronephrosis was diagnosed, and she was referred to our department for further evaluation. Intravenous pyelography (IVP) revealed bilateral hydronephrosis and hydroureters. Computerized tomography (CT) showed retention of ascitic fluid and thickening of the intestinal and bladder walls with contrast effects in the serosa and mucosa. Lasix-loaded renography showed that both kidneys were normal. Examination of a biopsy specimen revealed interstitial edema, fibrosis, and infiltration of inflammatory cells. Cystometry showed normal intravesical pressure. A diagnosis of lupus cystitis was made and administration of 40mg of prednisolone was started. The anemia was ameliorated, and thickening of the bladder and intestinal walls was no longer seen on CT. Hydronephrosis of the left kidney was less prominent. However, aggravation of the right ureteral stenosis was noted, and a stent was inserted in the stenosed ureter. Stenosis was successfully relieved by the stent, and internal drainage was established. The patient is still receiving steroids and is being followed at our department. Twenty-two reported cases of lupus cystitis in Japan are reviewed.

Adult↗

[Marked effectiveness of the LH-RH analogue in a case of prostate cancer with large lymph node metastasis].

A 78-year-old man visited our hospital complaining of pollakisuria, dysuria, and edema of lower extremities. Physical examination revealed a hard, fixed and fist size mass in the abdomen Lymph nodes of left supraclavicular fossa were hardly palpable. His prostate was larger than a hen's egg, stony hard and fixed in the pelvis on digital rectal examination (DRE). The prostate specific antigen (PSA) level was elevated to 584 ng/ml. Computerized tomography (CT) revealed enlarged retroperitoneal lymph nodes. Bone scan showed multiple abnormal uptake. Prostate biopsy showed poorly differentiated adenocarcinoma. Treatment with the LH-RH analogue was very effective. The retroperitoneal lymph nodes were no longer enlarged on CT. The prostate had become soft and was reduced to walnut size on DRE. The PSA level had decreased to within the normal range. The multiple abnormal uptake on the bone scan decreased. This is the 21st case of prostate cancer with large lymph node metastasis in Japan.

Adenocarcinoma↗