[Clinical use of the 27015B micro-endoscope].
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Biomedical subjects
Publications and source records attributed to M Maegawa.
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Sixteen patients with advanced evaluable urothelial cancer were treated with a chemotherapy regimen of cyclophosphamide, adriamycin and cisplatin (CAP). Cisplatin 50 mg/m2 and adriamycin 30 mg/m2 were given on the first day and cyclophosphamide 200 mg/m2 was given from the second to the fifth day. This course was repeated every 3 weeks. The objective response rate was 25% (4 of 16 patients), with 1 patient achieving complete remission. The survival time of responders was longer than that of nonresponders, although the difference was not significant (generalized Wilcoxon method). As side effects, nausea with vomiting (43.8%), renal dysfunction (6.3%), anemia (12.5%), leucopenia (12.5%), thrombocytopenia (25.0%), alopecia (68.8%), heart failure (6.3%) and peripheral neuropathy (6.3%) were noticed. One patient died of sepsis due to agranulocytosis and another died suddenly of heart failure.
Fundamental and clinical evaluations of ten anticancer drugs were performed. The required qualities of an anticancer drug ideal for bladder instillation therapy are thought to be as follows: (1) a high sensitivity for bladder tumor cells; (2) a pKa which provides a high percentage of nonionized molecules in a pH 6-7 solution; (3) a log P in the range from -0.4 to -1.2 or from -7.5 to -8.0; and (4) a molecular weight over 200.
The localization of neurons containing immunoreactive thyrotropin-releasing hormone (TRH) was examined in the hypothalamus of intact, propylthiouracil (PTU)-treated, and colchicine-treated adult rats. In intact animals, immunoreactive TRH neurons were occasionally found in the paraventricular and dorsomedial nuclei, and in the anterior and lateral hypothalamic areas. In PTU-treated animals, the cellular appearance of the hypothalamus with the exception of the paraventricular nucleus was almost similar to that of intact animals. In the paraventricular nucleus, only the cells localized in the periventricular and medial parvocellular subdivisions significantly increased in number and became hypertrophic in comparison with intact animals. The distribution of immunoreactive fibers in the hypothalamus was almost equal among the 3 animal groups with the exception of that in the median eminence, in which the fibers were most densely concentrated in intact animals, and most sparse in PTU-treated rats. The fibers projecting into the median eminence were distinguished into the periventricular and lateral pathways, which are derived from the neurons in the periventricular and medial parvocellular subdivisions of the paraventricular nucleus, respectively. Thus, among immunoreactive TRH neurons in the hypothalamus, only those in the periventricular and medial parvocellular subdivisions of the paraventricular nucleus may be involved in the hypothalamic-hypophysial-thyroid axis.
The immunoreactive CRF-neurons of the rat hypothalamus have been examined immunohistochemically employing anti-rat CRF serum. These neurons are confined to the paraventricular nucleus, dorsomedial-lateral hypothalamic area, and suprachiasmatic nucleus, and are, respectively, also immunoreactive to anti-Met-enk, -alpha-MSH, and -VIP sera. Intraventricular administration of colchicine (50 micrograms/5 microliters/rat) induces a dramatic enhancement of the immunostainability of the cell somata, and also accelerates the development of immunoreactivity of other stored peptides, especially in the paraventricular nucleus. The CRF-neurons respond to adrenalectomy by showing increased immunoreactivity and an increase in the number of cell bodies; in the dorsomedial-lateral area and suprachiasmatic nucleus, there is also an enhanced immunoreactivity for alpha-MSH and VIP, respectively. CRF-cells in the paraventricular nucleus become markedly hypertrophied, but do not show any enhanced immunoreactivity for Met-enk. Since the axons of the paraventricular neurons run to the median eminence, it is probable that they are involved with the endocrine control of hypophysial ACTH release. It is concluded that the CRF-containing neurons in rat hypothalamus consist of three types which are functionally and morphologically different.
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Appearance of immunoreactive corticotropin-releasing factor (CRF)-containing neurons was studied in developing hypothalamus of the rat by use of antisera against rat- and ovine CRF. These neurons were first recognized in the lateral and paraventricular nuclei on days 15.5 and 16.5 of gestation, respectively, when antiserum against rat CRF was employed. Antiserum against ovine CRF revealed the cells two days later exclusively in the latter nucleus. In both nuclei, the neurons increased in number with development. The neurons in the paraventricular nucleus appeared to project their immunoreactive processes to the median eminence via the periventricular and lateral pathways. In the median eminence, the immunoreaction with antiserum to rat CRF was first recognized in its anterior portion in the form of dots on day 16.5 of gestation but as beaded fibers in the external layer on day 17.5; these structures increased in amount with development in rostro-caudal direction. Although antiserum to ovine CRF was less potent in immunostainability than antiserum to rat CRF, it also revealed the beaded fibers in the median eminence on day 17.5 of gestation. Since evidence is available that the paraventricular nucleus is involved in corticotropin release, it is concluded that, in rats, the hypothalamic regulatory mechanism controlling the release of corticotropin initially appears on days 16.5-17.5 of gestation.
Our AFC regimen was originally developed to treat superficial bladder tumors. It consists of a daily intravesical administration of 20 mg Adriamycin (ADM) and 200 mg Cytosine arabinoside (CA) dissolved in 20 ml of sterilized distilled water, simultaneously with a daily rectal suppository of 750 mg tegafur (Futraful) for a total of 20 applications. Our study demonstrated the following characteristics of the AFC modality: (1) It is simple; (2) it is completed in 3 weeks, which is shorter than conventional bladder instillation therapy; (3) the effective rate is reasonable (70%); (4) no local side-effects were observed because the concentrations of ADM and CA were low; (5) interruption of therapy was unnecessary, because whatever general side-effects were caused, they disappeared within several days of completion of treatment.
A Tegafur suppository of 750 mg was administered daily to 20 patients with bladder tumors, whose ages ranged from 43 to 84 years (average age 63.7). Histological study revealed transitional cell papilloma in 6 cases, transitional cell carcinoma in 12 cases, squamous cell carcinoma in 1 case and malignant tumor with extensive necrosis in 1 case. The result of staging and grading was as follows: 8 cases of pTa, 5 cases of pT1, 9 cases of pT2, 1 case of pT3a, 2 cases of pT3b and 1 case of T4; an, 6 cases of G0, 6 cases of G1, 5 cases of G2, 2 cases of G3 and 1 case of unknown grade. According to Saitoh and Koyama's criteria, no cases showed complete response (0%), 5 cases partial response (25%), 3 cases minor response (15%), 10 cases no change (50%) and 2 cases progressive disease, making the total effective rate 25.0%. Some side effects were observed in 6 of the cases (30%): General malaise in 4 cases (20%), loss of appetite in 3 cases (15%), diarrhea in 1 case (5%), edema in 1 case (5%), anemia in 2 cases (10%), an elevation of both GOT and GPT in 1 case (5%) and thrombocytopenia in 1 case (5%). A recovery from these side effects was achieved after discontinuing the use of Tegafur suppositories.
A case of rhabdomyosarcoma of the urinary bladder in a child with urethral prolapse is reported. The patient was an 18-month-old girl and was admitted to our clinic with complaints of micturition pain, hematuria and tumor of the vulva. Histological examination revealed that this tumor was urethral prolapse. A grape-like tumor was demonstrated at bladder bottom by cystogram and cystoscopy. The histological pattern was embryonal type of rhabdomyosarcoma of the bladder. Combined chemotherapy with actinomycin D, adriamycin and cyclophosphamide has been started. A survey of Japanese literature on rhabdomyosarcoma of the bladder in children was done with reference to age, sex, site of tumor, symptom, histological findings, treatment and prognosis.
A combination therapy consisting of daily intrarectal administration of 1,500 mg of FT-207 suppository, daily or every three day bladder instillation of 40 mg adriamycin for a total of 20 applications, and once per week intramuscular administration of 5 KE OK-432 was described. The therapy was performed in 30 cases of advanced bladder cancer. The effectiveness evaluated by Karnofsky's criteria was as follows: 8 cases of 0-0, 2 of 0-A, 1 of 0-B, 2 of 0-C, 7 of 1-A and 10 of 1-B, showing an effective rate of 57%. Local pain was observed in 20 cases (67%), pancytopenia in 1 (3%), hepatitis in 4 (13%), stomatitis in 5 (17%) and anorexia in 6 (20%). From this clinical trial, it is presumed that combination therapy administering FT-207 intrarectally, adriamycin intravesically and OK-432 intramuscularly might be used for the treatment of advanced bladder cancer provided sufficient care is taken of general side effects.
The effect of preoperative bladder instillation (POI) and periodic prophylactic bladder instillation (PPI) of anticancerous drugs was evaluated in connection with the prevention of recurrent bladder tumors after surgery. A total of 191 patients with pTa or pT1 tumors including patients submitted to TURbt and partial cystectomy from January, 1967, to December, 1980, was chosen for the study. They were divided into the following 4 groups: Group A (49 cases) was treated with PPI and POI, Group B (11 cases) with PPI but not POI, Group C (46 cases) with POI but not PPI and Group D (85 cases) with neither PPI nor POI. POI was performed three times a week for a total of 20 applications of anticancerous drugs from two months before surgery. PPI was performed twice a month from one month after TURbt or parital cystectomy with a combination of 20mg of Mitomycin C and 1,000mg of 5-FU. The non-recurrence rate in these 4 groups was estimated by the actuarial method. The 3 year non-recurrence rates in Groups A,B,C and D were 95.4%, 90.9%, 44.0%, and 45.6%, respectively. The 5 year non-recurrence rates in Groups A,B,C and D were 82.4%, 81.0%, 32.0% and 35.1%, respectively. It is presumed from our study that PPI was effective in preventing the recurrence of bladder tumors. In comparison, POI showed a very limited effect and only in the first two years after surgery. No carcinogenic action on the bladder epithelium was observed from the topical use of Mitomycin C.
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The application of freeze-substitution (FS) and freeze-drying (FD) techniques and the protein A-gold-antibody complex immunocytochemical methods are described. The two tissue-preparation techniques produced excellent ultrastructure and topographical fixation of antigens when compared with conventional tissue-preparation techniques. In the FS preparation, however, occasional extragranular immunolabeling was recognized. This may suggest the leakage of antigens from the secretory granules. The FD procedure was considered the best, since such labeling was almost negligible. The protein A-gold-antibody complexes are easily prepared and label the antigens clearly. If the protein A-coated gold particles are saturated with antibodies, there is no interaction between gold particles. Thus, multiple antigens can be determined even in single secretory granules. In fact, we demonstrated intragranular colocalization of immunoreactive oxytocin, labeled with 50-nm gold particles, and immunoreactive methionine-enkephalin, labeled with 15-nm gold particles, in the axonal terminals of the FD-prepared rat neurohypophysis. This study demonstrates the value of the use of gold-antibody complexes for immunocytochemical labeling on FS- or FD-treated tissues.
Active immunization with the peptide segments rSMP-230 and YAL-198, corresponding to the hydrophilic extracellular domain of two human sperm antigens (rSMP-B and YWK-II, respectively), reduced fertility in female rats by different mechanisms. The anti-rSMP-230 antibody interferes with human and murine fertilization, and the anti-YAL-198 antibody blocks the development of mouse embryos. The authors examined in vitro at which stage the antibodies to rSMP-230 and YAL-198 were cytotoxic to murine embryos up to morula/blastocyst stage. Anti-rSMP-230 antibody was not cytotoxic to any stages. On the other hand, the anti-YAL-198 antibody arrested the growth of embryos at the 2-cell stage but not at more advanced developmental stages. When the anti-YAL-198 antibody was used, spotty staining was observed only on the surfaces of embryos that had arrested at the 2-cell stage. Unstained embryos, however, continued to develop normally. In contrast, the anti-rSMP-230 antibody stained murine sperm but failed to stain murine ova and embryos. The present results suggest that the human sperm components rSMP-B and YWK-II play important roles in sperm-egg interaction and early development of the embryo, respectively.
Sperm-immobilizing antibodies block human fertilization by interfering with the acrosome reaction (AR). To clarify the mechanism of blockage of AR by sperm-immobilizing antibodies, the authors examined their effects on the increase of intracellular free Ca2+ concentration induced by follicular fluids (Ca2+ influx) in spermatozoa and on their capacitation. Sperm-immobilizing antibodies did not suppress Ca2+ influx induced by follicular fluid, but they inhibited capacitation of human spermatozoa. Namely delta%AR (%AR after addition of an AR inducer--%AR before treatment) induced by progesterone was significantly (p < .0001) lower when spermatozoa were incubated in human tubal fluid medium cotaining antibody-positive serum (1.2%), compared to that when incubated in control medium (19.2%). Furthermore, the proportion of both spermatozoa that became capacitated and ones that had become capacitated decreased significantly (p < .0001) after 2, 4, and 6 h of incubation in medium containing antisperm antibody-positive serum, compared to those of spermatozoa incubated in control medium. In conclusion, sperm-immobilizing antibodies may be closely related to their blockage of capacitation.