Biomedical subjects

Y Kaburagi

Publications and source records attributed to Y Kaburagi.

47 records · Page 3Linked to original sources

PubMed1992

In vitro association of phosphatidylinositol 3-kinase activity with the activated insulin receptor tyrosine kinase.

We previously have shown that insulin treatment of cells greatly increases the activity of phosphatidylinositol (PI) 3-kinase in immunoprecipitates made with an antibody to phosphotyrosine. However, the association of PI 3-kinase activity with the activated insulin receptor is not significant under these conditions. In the present study, we have attempted to reconstitute the association of PI 3-kinase activity with the activated insulin receptor in vitro. PI 3-kinase activity does indeed associate with the autophosphorylated insulin receptor in our in vitro system. The autophosphorylation of the insulin receptor and/or its associated conformational change appear to be necessary for the association of PI 3-kinase activity with the receptor, since kinase negative receptor failed to bind PI 3-kinase activity. After binding, PI 3-kinase or its associated protein seems to be released from the activated receptor after the completion of its tyrosine phosphorylation by the receptor. Tyr960 in the juxtamembrane region of the insulin receptor beta-subunit seems to be involved in the association of PI 3-kinase activity with the receptor, but not C terminus region of the beta-subunit including two tyrosine autophosphorylation sites (Tyr1316 and Tyr1322). The in vitro assay system for the association of PI 3-kinase activity with the insulin receptor can be utilized to study the mechanism of interaction of these molecules and will be an useful method to detect other associated molecules with the insulin receptor.

Animals↗

PubMed1991

Infant botulism with Down syndrome.

A 4-month-old boy with Down syndrome and infant botulism is reported. He was admitted to our hospital with stridor and developed respiratory failure and generalized paralysis. Laboratory examination revealed botulinal toxin type A in his blood and feces. Clostridium botulinum organisms were found in the feces and in the honey which he had been fed. Anti-botulinal toxin was administered on the 10th day of illness. Artificial ventilation was given for 87 days and he survived. This is the 11th known case of infant botulism in Japan. It is possible that other cases remain undiagnosed.

Botulinum Antitoxin↗

PubMed1989

[Photodynamic therapy--its application for the treatment of esophageal cancer].

Effect of Photodynamic therapy (PDT) for esophageal cancer was discussed in this study. PDT has been performed on 9 cases of superficial esophageal cancer. All cases were followed periodically by endoscopy for 2 years 2 months to 6 years and no case has any local recurrence. But in 2 cases invaded submucosal layer, lymph node metastasis was recognized. We think PDT is one of the very effective therapies in the treatment of intramucosal cancer.

Aged↗

PubMed1989

[Efficacy of extended radical operation based on preoperative staging].

From 1985 to 1988, we have resected 203 cases of the thoracic esophageal cancer with right thoracotomy. Those 203 cases were classified as R3 (bilateral cervical, thoracic and abdominal node dissection), R2 + alpha (left cervical, thoracic and abdominal nodes dissection) and R2 (thoracic and abdominal node dissection) based on preoperative staging. The background of R3 mainly contained Iu cases, advanced cases, positive cases of upper mediastinal metastasis, and that of R2 mostly contained high aged and risk cases, though this group showed low LN metastasis. The incidence of postoperative complications were higher R3 greater than R2 greater than R2 + alpha in order. Pneumonia had no relationship to neck dissection. Recurrent nerve palsy was recognized in R3 group about 16%. Operative mortality mostly belong to high aged group over 70 y.or., noncurative cases and R3 group. The survival rate of C greater than 0 resected cases with right thoracotomy after 1985 showed some improvement compared with the cases of standard R2 dissection by right thoracotomy from 1980-1984. It showed no difference of the curative survival curve among R3, R2 + alpha and R2 groups. Thus, it is effective to improve the survival rate of resected esophageal cancer with our indication based on preoperative staging.

Abdomen↗

PubMed1988

[Multidisciplinary treatment of thoracic esophagus carcinoma based on preoperative staging].

Recently, with developments in CT scanning and endoscopic ultrasound (EUS), in addition to conventional ultrasound (US), significant advances have been made in the evaluation of preoperative staging. Evaluation of the presence of A3 invasion is made on the basis of X-ray, CT and EUS findings. In superficial cases of ep, mm or sm, EUS with particular reference to the X-ray and endoscopic appearance is very effective, and in our department the diagnostic accuracy in cases of mucosal lesions is 88%, while it is 84% in sm cases. Diagnosis of metastasis to cervical and abdominal lymph nodes is performed by US, while diagnosis of mediastinal lymph node metastasis is performed by EUS. The accuracy of US for detecting cervical and abdominal lymph node metastases, including those approximately 0.5 cm in size, is 95%, while that of EUS in the diagnosis of metastasis to mediastinal nodes is 89%. The 5-year survival of patients with lymph node metastasis significantly affects prognosis. Based on this, since 1985, extended dissection in the cervical, thoracic and abdominal regions has been carried out. Since 1985, some resected cases have been treated with pre- or postoperative adjuvant chemotherapy regimens, centered primarily on CDDP (majority of cases with CDDP + VDS). A significant improvement has been obtained in the 1-2-year survival of C greater than O resected cases treated since 1985, compared with cases in 1980-1984. This improvement is thought to be due to dissection of lymph nodes in the three major regions, based on more accurate preoperative evaluation and the introduction of postoperative adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

The possibility of aromatization of androgen in human prostate.

Aromatase in human prostate tissue was determined in homogenized human prostate (three BPH and two normal specimens) incubated with [1-beta-3H]androstenedione (radiometric method) or [1,2,6,7-3H]androstenedione (estrogen production analysis method) in the presence of NADPH. Using the former procedure, significant amounts of 3H2O, resulting from the release of 3H at the C-1 position during aromatization, were measured and these increased with incubation time and amount of tissue, whereas the amount of estrone and estradiol-17 beta resulting from the latter method and calculated from the 3H/14C ratio in preparations of purified crystal was very small. The preliminary results, which suggest that an androgen aromatase system exists in the human prostate, point to the need to further investigate the identity and properties of the metabolic products resulting from the conversion of androgen to estrogens and other metabolites.

Androstenedione↗

PubMed1986

[The regulation system of brain aromatase activity; effects of androgens on hypothalamic aromatase in the male rat].

Recently, some studies have found the greatest aromatase activity in brain areas associated with sexual differention and sexual behavior, namely the hypothalamic and limbic structures. We studied the regulation of aromatase activity in the hypothalamic area of male rats, using a sensitive in vitro assay which measures the amount of 3H2O formed by tissue homogenates during the conversion of [1 beta-3H] androstenedione to estrogen. After castration, hypothalamic aromatase activity was significantly decreased (P less than 0.01), and seminal vesicle (SV) and prostate (PR) weights were also significantly decreased (P less than 0.01). Castrated male rats were given testosterone (T), 5 alpha-dihydrotestosterone (DHT), 5 alpha-androstane-3 alpha, 17 beta-diol (A3 alpha), 5 alpha-androstane-3 beta and 17 beta-diol(A3 beta) in various doses (200-1000 micrograms/day) for 10 days, and were given 600 micrograms/day T, DHT, A3 alpha and A3 beta for various durations (1-10 days). We found that T, DHT and A3 alpha but not A3 beta reversed the effects of castration on the hypothalamic aromatase activity. The order of this reversible effect of androgens was as follows: T greater than or equal to DHT greater than A3 alpha. T, DHT, A3 alpha and A3 beta increased SV and PR weights, and the order of this effect was as follows: DHT greater than T greater than A3 alpha much greater than A3 beta. We administered the antiandrogen (flutamide) to intact male rats (8 mg/day for 6 days). Flutamide decreased hypothalamic aromatase activity at the same level as that of castrated rats. Likewise, administration of both flutamide and T to castrated rats blocked the T-induced increase in hypothalamic aromatase activity and accessory sexual organ weight. From these results, we suggest that T, DHT and A3 alpha regulated hypothalamic aromatase activity, that T was the most effective of the androgens, and that was different from peripheral androgen target organs.

Androgens↗

PubMed1984

[The metabolism of testosterone in the central nervous system (1). Analysis of testosterone metabolites in the anterior pituitary and hypothalamus using gas chromatography-mass spectrometry (GC-MS), and subcellular localization of testosterone converting enzyme].

The aim of this study was to identify accurately the structure of testosterone metabolites in the anterior pituitary and hypothalamus for the investigation of the mechanism of androgen action in the central nervous system. Tissue homogenate and cellular fraction of male rat anterior pituitary and hypothalamus were incubated with testosterone-4-14C and testosterone-19-CD3 (14C/D3 = 1) in the presence of NADH and NADPH. The incubation media were extracted, and they were separated using thin layer chromatography (TLC). Using autoradiogram of TLC, four main radioactive fractions were found on the TLC. The TFA or TMS derivatives of every fraction were analyzed using GC-MS. The main metabolites in the anterior pituitary were identified as 5 alpha-androstan-17-ol 3-one; androst-4-ene-3, 17-dione, 5 alpha-androstane-3 alpha, 17 beta-diol, 5 alpha-androstane-3 beta, 17 beta-diol, androst-4-ene-3 alpha, 17 beta-diol and androst-4-ene-3 beta, 17 beta-diol. The result in the hypothalamus was the same as that in the pituitary. The subcellular localization of metabolites in the anterior pituitary was as follows: 5 alpha-androstan-17-ol-3-one, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol were found in microsome; 5 alpha-androstane-3 alpha, 17 beta-diol and androst-4-ene-3 alpha, 17 beta-diol were found in soluble fraction. The result in the hypothalamus was the same as that in the pituitary.

Androstane-3,17-diol↗

PubMed1983

[Experimental and clinical studies on intravesical instillation therapy for bladder cancer].

Intravesical instillation therapy was performed in 155 cases of urinary bladder cancer. In 60% of the patients treated by therapeutic intravesical instillation, antitumor effects were observed. The patients who were given only the instillation therapy frequently had recurrence of the tumor in the same site within one year. Therefore, in such cases prophylactic instillation seems to be necessary. The preventive effect of intermittent instillation therapy given over a long period was superior to that of concentrated instillation therapy given during a short period. The rate of recurring bladder tumors decreased after instillation therapy. Eight cases that were cystoscopically nonvisual tumors but indicated positive cytology were treated by intravesical instillation therapy. In 5 of these cases cytology was negative after treatment.

Adolescent↗

PubMed1983

[Clinical study on prophylaxis of diacetyl-glucaro-(1-4) (6-3) dilactone for recurrence of bladder cancer].

In order to investigate the effect of Diacetyl-glucaro-(1-4) (6-3) dilactone to prevent post-operative recurrence of bladder cancer, we estimated the recurrent rate of 34 patients who were diagnosed as having bladder cancer and treated by several surgical methods and oral administration of the drug in our hospital during 1971 and 1980. The following results were obtained: The 6, 12, 18, 24, 30, 36 and over 36 months-recurrent rates were 3.1%, 26.4%, 32.5%, 32.5%, 32.5%, 46% and 46%. In control group, they were 10%, 23.3%, 34.8%, 46.2%, 73.1%, 73.1% and 100% In a 24 month follow-up, there was no difference of recurrent rate between the group receiving the drug and control group: a recurrent rate of administrated group was lower than that of the control after 24 months. The recurrent rate of the group receiving Diacetyl-glucaro-(1-4) (6-3) dilactone combined with instillation was lower in a 2 year follow-up. It was anticipated that the combined therapy (Diacetyl-glucaro-(1-4) (6-3) dilactone administration and intravesical instillation of anticancer drugs) was useful in order to prevent recurrence of bladder cancer.

Adult↗

PubMedDate not supplied

The potential significance of aromatase in the etiology and treatment of prostatic disease.

Prior to the present conference on aromatase, reports in the literature on prostatic aromatase have been scattered over time, few in number, and the results have been widely divergent. Moreover, several participants at this conference have reported unpublished data that failed to detect the existence of androgen aromatase in the prostate of man and other species. While papers and posters presented at this conference have added new information to this field, there would still appear to be no consensus as to the biological significance, if any, of the putative androgen aromatase system or the practical importance of inhibitors of prostatic and/or peripheral aromatase as a treatment modality for benign prostatic hyperplasia (BPH). Thus, it would be difficult to predict at this time the ultimate impact which current prostatic aromatase investigations will eventually have on our understanding and treatment of prostatic disease. To summarize the status of our current understanding of aromatase as it relates to prostatic function and disease, it would be safe to note that this field is virtually wide open for researchers to explore, both in terms of the future role that aromatase inhibitors may have in clinical investigations and in terms of the functional significance of aromatase, if any, in the normal prostate as well as in the pathogenesis of BPH and prostate cancer. Clearly, the widely divergent results currently available in the literature must reflect, in part, differences in methodology, anatomy, tissue types, the relative amounts of stroma and epithelium in specimens analyzed, the cellular and tissular (normal, BPH, and carcinomatous) heterogeneity encountered in clinical specimens, and the pharmacologic features of aromatase inhibitors tested.

Aromatase↗