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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 487 records · Page 27Linked to original sources
PubMed1995

[A dose-comparative study on TAP-144-SR, an LH-RH agonist depot formulation, in premenopausal patients with advanced or recurrent breast cancer. TAP-144-SR Breast Cancer Study Group].

A comparative phase II study was performed with different doses of TAP-144-SR in ER-positive or ER-unknown premenopausal patients with advanced or recurrent breast cancer. One hundred and six patients were randomly allocated to either 3.75 mg or 7.5 mg treatment by a centralized telephone registration system. TAP-144-SR was administered sc at 4-week intervals for 12 weeks (a total of 3 injections). Ninety-five cases were evaluated with the response rate of 30.4% (14/46) in the 3.75 mg group and 24.5% (12/49) in the 7.5 mg group, respectively. Serum estradiol was decreased to postmenopausal level (< 30 pg/ml) within 3-4 weeks after the first dose in the both dose groups, and this suppression was maintained throughout the treatment period. The adverse reactions most frequently observed were climacteric disturbances like hot flashes which was likely to be due to the hypoestrogen status. In conclusion, there was no significant difference between both dose groups in terms of response rates, adverse effects, and hormonal suppression. Therefore, the lower dose is recommended for the further study.

Adult↗
PubMed1995

[Long-term clinical study on TAP-144-SR, an LH-RH agonist depot formulation, in premenopausal patients with advanced or recurrent breast cancer. TAP-144-SR Breast Cancer Study Group].

Efficacy and safety of long-term treatment with an LH-RH agonist, TAP-144-SR were studied in premenopausal patients with advanced or recurrent breast cancer. The drug was given sc every 4 week at the dose of 3.75 or 7.5mg. The best objective response rates were 37.0% (17/46) in 3.75mg group, 30.6% (15/49) in 7.5mg group, respectively. The median duration of 12 PR patients in 3.75mg group was 280 (range: 84-830+) days. Serum estradiol level was maintained at < 30pg/ml in most patients given 3.75mg or 7.5mg as scheduled. There was no adverse reactions specific to the longterm administration subsequent to the foregoing 12-week administration study in both dose groups. In conclusion, TAP-144-SR is expected to be one of the first line therapies for patients with premenopausal breast cancer.

Adult↗
PubMed1995

[Laparoscopic unroofing of a renal cyst].

Laparoscopic unroofing of a renal cyst was performed in 13 cases of simple cysts of 48 ml. to 678 ml. (mean: 217 ml.) preoperatively measured by ultrasonography from April, 1994 through April, 1995 at our Department of Urology. Under general anesthesia, the renal cyst wall was resected as close as possible to the renal parenchyma by the laparoscopic technique. The postoperative outcome was evaluated in 12 of 13 cases, except for the one case converted to laparotomy because of uncontrollable bleeding from the resected site of the renal parenchyma. Three months after the operation, complete disappearance of the renal cyst was noted by CT scanning in 10 of the 12 cases. In the remaining 2 cases, the renal cyst was still in existence despite the apparent reduction of the cyst volume. In one case in which a somewhat large cyst remained, sclerotherapy using minocycline was carried out. No serious complications during the operation were observed, but in one case with uncontrollable bleeding as mentioned above, the postoperative course was uneventful. These findings indicate that, the laparoscopic unroofing of a renal cyst is a safe and useful procedure for a relatively large renal simple cyst, therefore this approach seems to be acceptable, and before long it will be an ordinary urological operation.

Aged↗
PubMed1995

[Dose-volume histogram comparison among techniques of linac stereotactic radiosurgery].

The aim of this study was to analyze the three-dimensional dose distributions produced by various techniques used in current radiosurgery treatments by means of dose-volume histograms (DVH). Off-center ratio and tissue-peak ratio from 6-MV X-rays through additional cylindrical collimators were measured in advance for dose calculation. The use of the diamond detector and beam profile film dosimetry in small fields were certified. The impact of arc number, arc geometry, and field size on the dose distribution in a spherical phantom was evaluated through the use of DVH. These were calculated for a) four arc irradiations with collimator sizes of 5, 10, 20 and 30 mm in diameter, and b) for single-plane rotation, four or eleven multiple non-coplanar convergent arcs, dynamic rotation and precessional converging radio-therapy (PCR) with a field size of 20 mm. PCR is performed in the sitting position with the patient seated on a special treatment chair, which is rotating continuously while the gantry moves from the top to the center of the chair rotation. Most of the differences between techniques were found in a range of less than 40% of the maximum dose. Multiple non-coplanar convergent arcs with four or eleven arcs and PCR performed similar result in DVH, while single-plane rotation revealed almost unacceptably shallow dose falloffs. The DVH of dynamic rotation was between that of single-plane rotation and the other three methods.

Humans↗
PubMed1995

Synthesis of oligonucleotide having a bent structure by incorporation of an interresidually cyclized uridylyl (3'-5')uridine unit.

The chemical synthesis and conformational properties of interresidually cyclized uridylyl(3'-5')uridine derivatives were studied in order to introduce a stable turn structure into oligonucleotides. These cyclized molecules were analogs of uridylyl(3'-5')5-[methylamino(methyl)]-uridine which is the component of the U turn structure of tRNAarg E. coli. The conformational properties of these cyclic dinucleoside monophosphates were studied using NMR and CD spectroscopy with the aid of molecular mechanics and molecular dynamics simulations. These experiments indicated that the turn conformation could be stabilized by introducing a cyclic structure as expected. On the basis of these results, the chemical synthesis of phosphoramidite units of these cyclic dinucleoside monophosphate derivatives were studied to construct oligonucleotides having a stable bent structure.

Circular Dichroism↗
PubMed1995

Synthesis and properties of oligo-omega-amino acids derivatives containing nucleosides.

Nucleic acid analogs, that consist of oligo-omega-amino acids as main chains were synthesized. At first, hydroxyl group of deoxy and ribonucleic acid was converted into amino or carboxylic acid group. Then, amino acid derivatives containing aminonucleoside or nucleoside-5'-carboxylic acid at alpha-position were synthesized. Amino acids used in this paper were L-glutamic acid, L-2-amino adipic acid (L-homo glutamic acid), L-ornithine, and L-lysine. These amino acid derivatives containing nucleoside were oligomerized by activated ester methods and Merrifield's solid phase synthesis. The properties of these analogs were studied and compared with oligo-alpha-amino acid derivatives containing nucleoside at omega-position.

Amino Acids↗
PubMed1994

Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis.

Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The pathophysiological role of interleukin 8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), was explored in an animal model of acute immune complex-mediated glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but significant number of neutrophils in glomeruli and the fusion of epithelial cell foot processes. Concomitantly, urinary levels of protein and albumin increased markedly (3.20 +/- 0.97 and 1.39 +/- 0.53 mg/h, respectively) compared with those of untreated animals (0.77 +/- 0.21 and 0.01 +/- 0.01 mg/h, respectively). Anti-IL-8 antibody treatment decreased the number of neutrophils in glomeruli by 40% and dramatically prevented the fusion of epithelial cell foot process. Furthermore, treatment with anti-IL-8 antibody completely normalized the urinary levels of protein and albumin (0.89 +/- 0.15 and 0.02 +/- 0.01 mg/h, respectively). These results indicated that IL-8 participated in the impairment of renal functions in experimental acute immune complex-mediated glomerulonephritis through activating as well as recruiting neutrophils.

Acute Disease↗
PubMed1994

Conventional Dose CAF Therapy versus Low Dose Adriamycin Therapy in the Treatment of Advanced Breast Cancer.

A controlled randomized trial was conducted to compare the effectiveness of a conventional dose of CAF therapy with that of a low dose of adriamycin (ADR) therapy for the treatment of advanced Breast Cancer. The doses of medication for the conventional CAF therapy were 100 mg/body of cyclophosphamide (CPA) p.o. daily fort wo weeks, 30 mg/m(2) of ADR and 500 mg/m(2) of 5-fluorouracil (5-FU) i.v. on days 1 and 8 for induction, and 200 mg/body of 5-FU and 20 mg/body of tamoxifen (TAM) p.o. daily for maintenance. Those for the low dose ADR therapy were 15mg/m(2) of ADR i.v. at two-week intervals for one year and 200 mg/body of 5-FU and 20 mg/body of TAM p.o. daily. Eighty patients were entered in this trial. All patients were randomly divided into two groups with stratification for estrogen receptor status. Of 78 patients among them, 38 undergoing the CAF therapy and 40 undergoing the low dose ADR therapy, were evaluated for efficacy assesment. The background factors analyzed were well balanced in both groups. The response rate was 47%(6CR, 12PR out of 38) in the CAF group and 43% (3CR, 14PR out of 40) in the low dose ADR group. There was no significant difference in response rates and survival rates as determined by the Kaplan Meier method between the two groups. The CAF therapy had significantly more toxicity than the low dose ADR therapy. Therefore, it was concluded that this low dose ADR therapy can be regarded as a treatment of choice for advanced breast cancer.

Journal Article↗
PubMed1994

Effect of an angiotensin II receptor antagonist, CV-11974, and its prodrug, TCV-116, on production of aldosterone.

In dispersed rabbit adrenocortical glomerulosa cells, a non-peptide angiotensin II (AT1) receptor antagonist, CV-11974 (10(-10)-10(-5) M), competitively inhibited angiotensin II- or angiotensin III-stimulated aldosterone production, whereas PD123177, an angiotensin AT2 receptor antagonist, did not. CV-11974 inhibited aldosterone production induced by 4 mM K+ but not by 12 mM K+. CV-11974 had no effect on adrenocorticotropic hormone-stimulated aldosterone or corticosterone production, but inhibited angiotensin II-stimulated corticosterone production. In the rat, TCV-116, the prodrug of CV-11974, (0.1 and 1 mg/kg, p.o.) markedly reduced the elevation of both plasma aldosterone concentration and blood pressure induced by i.v. infusion of angiotensin II. In spontaneously hypertensive rats, TCV-116 at daily p.o. doses of 0.1, 1 and 10 mg/kg for 2 weeks caused a dose-dependent reduction of blood pressure and plasma aldosterone concentration without affecting plasma corticosterone. Thus, TCV-116 inhibited the induction of aldosterone production by not only exogenous but also endogenous angiotensin II.

Administration, Oral↗
PubMed1994

Phorbol 12-myristate 13-acetate stimulates proliferation and ductal morphogenesis and inhibits functional differentiation of normal rat mammary epithelial cells in primary culture.

The effect of the tumor promoter phorbol 12-myristate 13-acetate (PMA) on proliferation and differentiation of normal mammary epithelial cells from 50-day-old virgin rats was investigated using a model system that allows for full morphological and functional development of the cells. In this model, mammary epithelial cells are grown within a reconstituted basement membrane in a defined serum-free medium. PMA at a concentration of 10(-6) M effected translocation of protein kinase C from cytosol to membrane. At the same concentration, it stimulated cell proliferation both in the presence and absence of EGF, and this stimulation was observed even when PMA exposure was limited to 15 min at the time of each media change. In contrast to the effect on proliferation, PMA at concentrations of 10(-7) and 10(-6) M inhibited functional differentiation as assessed by casein accumulation. Phorbol 12,13-dibutyrate at 10(-6) M also stimulated proliferation and inhibited casein accumulation and was more effective than PMA in both cases. In contrast, the nonactive tumor promoter 4-alpha PMA had no effect on either proliferation or differentiation. One of the most striking effects of PMA was its ability to stimulate an atypical ductal morphogenesis, as manifested by the formation of intricate web-like colonies, and to inhibit the development of the well-differentiated alveolar-like multilobular colonies. PMA was also shown to completely suppress the growth of the squamous-like colonies that develop when EGF is absent or deficient. These effects of phorbol esters in mammary epithelial cells to stimulate proliferation, inhibit functional differentiation, and stimulate the development of ductal colonies are consistent with the suggestion that the signal transduction pathways evoked by PMA could act to stimulate the growth of initiated cells or render normal cells more sensitive to carcinogen.

Animals↗
PubMed1994

Risk factors influencing the short-term results of gastroduodenal perforation.

The purpose of this study was to evaluate the risk factors influencing the short-term results of gastroduodenal perforation to determine the optimal treatment for reducing mortality. A total of 136 patients were retrospectively reviewed and the prognostic factors were examined. Seven patients died within 30 days, with an overall mortality rate of 5.1%. Mortality was significantly worse in those aged 50 years or more, when the leukocyte count was less than 9,500/mm3, when treatment was delayed more than 12h after perforation, in cases of preoperative shock and renal failure, and when associated with liver cirrhosis or an immunocompromised state. Tolerance to the time delay was inversely proportional to age, while the deaths in patients aged 65 years or younger were related to serious concurrent diseases. Shock and renal failure occurred most often in elderly patients as a result of delayed surgery, and the leukocyte count was an age-dependent prognostic indicator. Thus, age, the time interval between perforation and treatment, serious concurrent disease, shock, and renal failure were presumed to be the most important prognostic factors. Although definitive operations were performed on low-risk patients with an acceptably low mortality, it remains to be determined whether simpler procedures should be adopted for high-risk patients.

Adolescent↗
PubMed1994

An immunohistochemical study of glucagonoma conducted on the metastatic lymph nodes from a patient with recurrent metastatic glucagonoma: report of a case.

In this report, we briefly present the case of a 67-year-old woman who developed recurrent glucagonoma with lymph node metastasis. An immunohistochemical study of the metastatic tumor revealed immunoreactivity of glucagon and protein kinase C (PKC)-alpha, -beta, and -gamma in the tumor cells, two types of which were seen by electron microscopy. One type had abundant secretory granules and mitochondria, while the other had few granules and mitochondria. Some granules were similar to typical A cell granules and others were atypical. An immunoelectron microscopic demonstration revealed PKC-alpha, -beta, and -gamma immunostaining in the cytoplasm of all the tumor cells, while some secretory granules had PKC immunostaining, and others had no immunostaining. Thus, it appears that metastatic glucagonoma and its associated granules are composed of two types of mature and immature cells or granules. As immunoreactivity of PKC-alpha and -gamma was found in the tumor cells, but not in the normal A cells of the islets of Langerhans, the PKC subspecies alpha and gamma, which are not present in normal pancreatic A cells, may exist in human glucagonoma cells.

Aged↗
PubMed1994

Coexistence of ochronosis and rheumatoid arthritis.

We describe a 64-year-old female patient with ochronosis and rheumatoid arthritis. Magnetic resonance imaging of the spinal column disclosed the destruction of vertebral disks, and a bony bridging in Th12 to L2. In addition, we observed joint space narrowing in the wrists as well as among the carpal bones, positive rheumatoid factor and the presence of rheumatoid nodules, in which the histological findings were compatible with those of rheumatoid arthritis. The co-existence of these two diseases has not yet been previously reported. Pre-existing ochronotic arthropathy might have masked the manifestation of rheumatoid arthritis and made the diagnosis of rheumatoid arthritis rather difficult.

Arthritis, Rheumatoid↗
PubMed1994

Additive two DMARD therapy of the patients with rheumatoid arthritis.

From the beginning of 1987 to the end of 1989, 72 rheumatoid arthritis patients (RA) whose disease could not be controlled by a single disease modifying antirheumatic drug (DMARD) were selected for the trial treatment. They continued the DMARD treatment used initially at its regular dose, and then started another DMARD regimen at 1/3 to 1/2 of the regular dose as an additive DMARD treatment, which we have designated as Additive Two DMARD Therapy (ATDT). The patients were followed until the end of 1992. In the 3 months of ATDT, the effectiveness of ATDT was obtained in 42 (58.3%) patients who showed more than a 30% decrease in the initial Lansbury's activity index (AI). The rate of side effects at 3 months were 5.6%. Tiopronin, bucillamine or salazopirine added to gold sodium thiomalate or tiopronin were suggested as the recommended DMARD combinations for ATDT. The suppressive effects on AI, ESR, CRP and rheumatoid factor continued for as long as 18 to 24 months. The mean period of ATDT was 21.7 months and that at which ATDT proved useful was 31.9 months. A discontinuation of the first DMARD treatment without any following disease aggravation was obtained in 10 of 15 patients whose disease activity had been sufficiently suppressed for longer than a year. In conclusion, ATDT was suggested to be a useful way of treating RA patients whose disease activity could not be controlled by a single DMARD treatment, as well as a way of evaluating the next DMARD while the ongoing DMARD was observed to gradually lose its initial drug effect.

Adult↗