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Biomedical subjects

Y Akasaka

Publications and source records attributed to Y Akasaka.

At least 19 recordsLinked to original sources

Different effects of pemphigus antibody and plasmin on the distribution of keratin intermediate filaments and desmoplakins between cultured oral and epidermal keratinocytes.

In order to clarify the molecular mechanism of blister formation in oral mucosa in pemphigus vulgaris (PV) comparing with that in epidermis, we analyzed the effects of PV serum on the distribution of keratin intermediate filaments (KIFs) and desmoplakins in oral as well as epidermal cultured keratinocytes by immunofluorescence microscopy using anti-keratin and anti-desmoplakin I/II monoclonal antibodies. After incubation with PV serum for 96 h at 37 degrees C, clusters of anti-keratin positive dots were formed around the nucleus in some of the keratinocytes from normal gingiva and soft palate but not in keratinocytes from tongue and skin, and desmoplakins also changed their distribution from linear arrangement at cell-cell contacts to clusters of dots around the nucleus in gingiva but not in epidermal keratinocytes. The dotted structures similar to those induced by pemphigus serum were formed also by incubation with human plasmin in gingival keratinocytes. However, no dot-formation of keratins was induced in these cells after incubation with trypsin. Furthermore, in epidermal keratinocytes, no keratin-dot formation was observed even after incubation with plasmin or trypsin. These results suggest that the dotted structures of KIFs caused by PV serum and plasmin might be a feature characteristic for the response of oral keratinocytes to PV serum and that there are some distinct differences in susceptibility to, and mode of, bulla formation between oral epithelium and epidermis.

Antibodies

Primary esophageal non-Hodgkin's lymphoma.

A 77-year-old woman with primary esophageal non-Hodgkin's lymphoma in clinical stage IEA (Ann Arbor Classification) developed pain and difficulty in swallowing. An upper gastrointestinal examination revealed a submucosal tumor from the upper to the middle portion of the esophagus. Histopathological examination at endoscopic biopsy with endoscopic partial incision showed non-Hodgkin's lymphoma (diffuse type--large cell). Immunohistological examination of tumor cells disclosed LCA (+), CD3(DAKO) (+), MT1 (+), UCHL1 (+), MB1 (+), MxPanB (-) and EMA (-) reactivity and showed T cell lymphoma. The clinical stage was determined to be IEA after further work-up. Improvement of swallowing difficulty and esophageal findings on upper gastrointestinal series were noted after modified CHOP therapy and radiotherapy (total 50 Gy).

Aged

Genomic changes in the WT-gene (WT1) in Wilms' tumors and their correlation with histology.

The authors studied genomic changes in unilateral Wilms' tumors by using WT33, a candidate cDNA for the tumor, and their correlation with histology. By Southern blot analysis, three cases of genomic deletions of both alleles were found in 25 tumors. The three tumors that showed genomic deletions were histologically classified as triphasic nephroblastic Wilms' tumor and one of them was associated with intralobar nephroblastomatosis and a rhabdomyomatous component. In one case, the WT1 gene was totally deleted, in another case, the 3' region of the gene was partially deleted, and in the last one, the deletion of DNA was intragenic. This is the first report of a comparison of genomic alteration with histopathology. These findings show new aspects of the role of the WT1 gene in the development of Wilms' tumor.

Blotting, Southern

[Clinical evaluation of ondansetron (injection of a single intravenous dose) against nausea and emesis associated with anti-cancer drugs--dose-finding study in patients receiving cisplatin].

We examined anti-emetic effects, safety and the optimal dose of Ondansetron Injection given in a single intravenous dose in patients receiving a single high dose of cisplatin in randomized controlled comparative study using telephone registration. Ondansetron was injected intravenously in a single dose of 4 mg, 8 mg or 12 mg, at 15 minutes before administration of cisplatin. Nausea and emesis were observed for 24 hours after administration of cisplatin. Efficacy rate of inhibitory effects on nausea and emesis were 76% (19/25 cases) in the 4 mg dose group, 57% (12/21 cases) in the 8 mg dose group and 83% (20/24 cases) in the 12 mg dose group, without a statistically significant difference among 3 dose groups. Hence, it was estimated that the low dose of 4 mg was adequate to exert satisfactory anti-emetic effects. No clear relationship between onset time of the initial emetic episode and plasma concentrations of Ondansetron was found in 16 cases of the 4 mg dose group, 11 cases in the 8 mg dose group and 15 cases in the 12 mg dose group. Side effects observed during this study period were headache and diarrhea in 1 case in the 12 mg dose group. Both symptoms were mild and resolved without treatment. No abnormal findings attributable to Ondansetron were observed in clinical laboratory test. From the above, it was considered that Ondansetron given by a single intravenous injection was highly effective to inhibit nausea and emesis induced by cisplatin, and was highly safe. As to the dose, 4 mg once daily was considered to be adequate for prophylaxis of cisplatin-induced nausea and emesis.

Adult

[Examination of anti-emetic effect, safety and usefulness of single oral dose of ondansetron tablet in nausea and emesis induced by anti-cancer drugs--dose-finding study of ondansetron tablet in patients receiving non-platinum anti-cancer drugs].

Inhibitory effects on acute nausea and emesis, safety and usefulness of a single oral dose of Ondansetron tablet were evaluated in 3 different dose levels for comparison by telephone registration system, in patients receiving non-platinum anti-cancer drugs. A single dose of ondansetron at 4 mg, 8 mg or 12 mg was given orally at 2 hrs before the initial administration of anti-cancer drugs. The patients were observed for 24 hours after administration of anti-cancer drugs, for occurrence of nausea and emesis. Efficacy rates of inhibitory effects on nausea and emesis were 83.3% (10/12 cases) in 4 mg dose group, 78.6% (11/14 cases) in 8 mg dose group and 84.6% (11/13 cases) in 12 mg dose group, without statistically significant difference. Side effects were observed in 3 cases (headache, cold feeling and trembling in limbs, sleepiness) in 12 mg dose group, but these symptoms were not severe and disappeared after several hours or several days. No abnormality in clinical laboratory findings attributable to Ondansetron was observed. From the above, it was considered that Ondansetron was a clinically useful anti-emetic for nausea and emesis induced by non-platinum anti-cancer drugs and that 4 mg once daily was the optimal dose.

Administration, Oral

[Anti-emetic effect and safety of consecutive use of ondansetron injection in cisplatin-induced nausea and emesis].

Anti-emetic effect, safety and clinical usefulness of Ondansetron injection given in the dose of 4 mg once daily by intravenous administration for 3-5 consecutive days were examined in patients receiving a high single dose (not less than 50 mg/m2 or over 75 mg/body) and lower multiple doses (over 15-20 mg/m2 once daily, for 3-5 consecutive days) of cisplatin. Efficacy rates of inhibitory effects on nausea and emesis in patients receiving the high single dose of cisplatin were 76% on the 1st day, 67% on the 2nd day and 78% on the 3rd day, the average being 71% (86/121 cases) for the 3 days. Those in patients receiving lower multiple doses of cisplatin were 83% on the 1st day, 78% on the 2nd day, 61% on the 3rd day, 65% on the 4th day and 57% on the 5th day, the average being 72% (13/18 cases) for the 3-5 days. Side effects were observed in 15 cases out of 207 (1st course, 182 cases; 2nd course, 21 cases; 3rd course, 4 cases), and major symptoms were headache and fever. Also, abnormalities in clinical laboratory findings attributable to Ondansetron were observed in 13 cases, mainly consisting of elevation of the hepatic function values. From the above, Ondansetron injection which showed sufficient anti-emetic effects on acute emesis and delayed emesis induced by a high single dose or lower multiple doses of cisplatin with its once daily intravenous dose given for 3-5 consecutive days, were considered a safe and clinically useful anti-emetic.

Aged

[Examination of anti-emetic effect and safety of multiple intravenous doses of ondansetron in patients receiving nonplatinum anti-cancer drugs].

Anti-emetic effects, safety and usefulness of Ondansetron given intravenously at 4 mg once daily for consecutive 3-5 days were investigated against nausea and emesis induced by non-platinum anticancer drugs. Efficacy rates in control of nausea and emesis were 59% (20/34 cases) and 68% (23/34 cases), respectively. The efficacy rate for inhibition of nausea and emesis, calculated based on the control of nausea and emesis, was 68% (23/34 cases). Adverse events (headache and constipation) were observed in 1 case and abnormal change in clinical laboratory findings (increase in eosinophil count) in another case. Out of 42 cases in which safety was evaluated, 41 (98%) cases were assessed as "no problem in safety." However, one case with side effect was assessed as a "Minor problem in safety." From the above, it was confirmed that Ondansetron injection exerted excellent inhibitory effects against nausea and emesis induced by non-platinum anti-cancer drugs, and this drug was a highly safe and useful anti-emetic.

Adolescent

[Investigation of anti-emetic effect of ondansetron tablet in multiple doses on nausea and emesis associated with cisplatin].

The anti-emetic effects, safety and usefulness of ondansetron, a 5-HT3 receptor antagonist, given orally once daily for 3-5 consecutive days, were investigated in patients receiving a high single dose (greater than or equal to 50 mg/m2 or 75 mg/body) or lower multiple doses (greater than or equal to 15-20 mg/m2/day for 3-5 consecutive days) of cisplatin. Ondansetron 4 mg was administered orally once daily for 3-5 consecutive days. Efficacy rates in controlling nausea and emesis over the 3-5 days were 77.3% (17/22 cases) and 66.7% (6/9 cases) in patients receiving a high single dose and lower multiple doses of cisplatin, respectively. Side effects were observed in 2 cases (headache and elevation of blood pressure in one case and only headache in the other case.). Abnormality in clinical laboratory findings was observed in 1 case. From the above, ondansetron, showing high efficacy by oral administration 4 mg once daily for 3-5 consecutive days, without any problem in safety, was considered to be a useful anti-emetic agent.

Administration, Oral

[Examination of inhibitory effect, safety and usefulness of SN-307 (ondansetron) administered orally once daily for 3-5 consecutive days on nausea and emesis associated with non-platinum anti-cancer drugs].

We examined the anti-emetic effect, safety and usefulness of ondansetron hydrochloride, a selective 5-HT3 receptor antagonist, given orally once daily at the dosage of 4 mg, for 3 to 5 consecutive days to patients with nausea and emesis induced by non-platinum anti-cancer drugs such as cyclophosphamide, doxorubicin and carboplatin. Out of 84 cases where anti-emetic effects were evaluated, numbers of cases assessed as excellent and good were 36 (83.3%) and 34 (40.5%), respectively, the efficacy rate being 83.3% (70/84). Side effects, such as moderate constipation (3 cases) and mild headache (3 cases), were observed in 8/85 cases (9.4%). Abnormalities in clinical laboratory findings including elevation of hepatic function and uricacid values and increase in eosinocyte counts, were observed in 3/85 cases (3.5%). As to overall safety, 78/85 cases (91.8%) were evaluated as having no problem in safety, and 7/85 cases (8.2%), as having minor problem in safety. As to clinical usefulness based on anti-emetic effect and overall safety, out of 79 cases the drug was assessed as very useful in 29 cases (36.7%) and useful in 35 cases (44.3%), the rate of "useful" or above being 81.0% (64/79). Furthermore, when ondansetron was administered in 3 courses of chemotherapy, though the number of patients was small, it was shown that anti-emetic effect of ondansetron did not decline and no problem in safety was observed. From the above, ondansetron which exerted adequate anti-emetic effect in 4 mg once daily doses was considered as a useful and safe anti-emetic in treatment of nausea and emesis associated with cancer chemotherapy.

Administration, Oral

[Evaluation of SN-307 (ondansetron), given intravenously for the treatment of nausea and vomiting caused by anticancer drugs including cisplatin-open study].

The anti-emetic effect, safety and clinical usefulness of ondansetron for the treatment of nausea and vomiting caused by anticancer drugs including cisplatin, was evaluated by a multi-institutional study in patients with various malignancies. In this study, ondansetron was given intravenously with mainly a single dose of 4 mg to intervene nausea and vomiting. 1. Efficacy ratio of overall effects on nausea and emesis observed for 24 hours after treatment was 69.8%. 2. No side effect was observed. Laboratory tests showed temporary elevation of serum uric acid level in 1 patient in the group given 4 mg. 3. From these results, it seems that ondansetron, given intravenously after initial vomiting, was highly safe and clinically useful anti-emetic for the treatment of nausea and vomiting associated with anti-cancer drugs.

Adult

[Anti-emetic effect and safety of single dose of ondansetron injection in double-blind comparison study with placebo].

In order to make an objective evaluation of anti-emetic effect, safety and usefulness of ondansetron injection in nausea and vomiting associated with cancer chemotherapy, we carried out a double-blind placebo controlled comparative study in patients receiving high-single dose (50 mg/m2 or more) of cisplatin. Either 4 mg of ondansetron or saline injection was given intravenously at 15 min. before administration of cisplatin. If anti-emetic effect of the test drug was insufficient, an additional dose of 4mg of ondansetron was given intravenously, as the rescue medication. Ondansetron was significantly superior to placebo in anti-emetic effect (p < 0.001). Efficacy rates were 66.7% (22/33 cases) in ondansetron and 20.0% (6/30 cases) in placebo groups. Seven and 21 cases required rescue medication with 4 mg single intravenous dose of ondansetron due to insufficiency of anti-emetic effect, in ondansetron group and placebo group, respectively. Thus the number of patients who required rescue medication was obviously greater in placebo group than that in ondansetron group. The rates of inhibitory effect of rescue medication on nausea and emesis were 14.3% (1/7 cases) in ondansetron group and 61.9% (13/21 cases) in placebo group. Side effects were observed in 1 case (eruption) in ondansetron group and in 2 cases (headache, diarrhoea; 1 case each) in placebo group. Furthermore, fever developed in 1 case in placebo group after the rescue medication. Elevation of total bilirubin value was observed in 2 cases in ondansetron group and 1 case in placebo group, however, these changes were mild and did not pose noteworthy clinical problem. From these results, ondansetron was shown to possess an excellent anti-emetic effect on nausea and emesis induced by highly emetogenic anti-cancer drugs, such as cisplatin, and to have no problem in safety, and thus it was considered to be a useful anti-emetic agent.

Adult

[Anti-emetic effect and safety of ondansetron tablet in double-blind comparison with placebo].

Ondansetron, a selective 5-HT3 receptor antagonist, has already been reported to have a marked effect to alleviate or prevent nausea and vomiting associated with cancer chemotherapy, after its intravenous administration. The present study was planned to examine the usefulness of its tablet form, which was prepared for the convenient use in outpatients receiving chemotherapy. In order to make an objective evaluation of anti-emetic effect and safety of ondansetron 4 mg tablet, this study was conducted in double-blind comparison versus placebo in patients receiving cisplatin at a single dose of 50mg/m2 or higher. Either 4 mg of ondansetron or placebo (lactose tablet) was administered orally once at 2 hrs prior to administration of cisplatin. If any satisfactory anti-emetic effects were not obtained, 4 mg of ondansetron injection was given once intravenously as a rescue medication. The inhibitory effect on nausea and vomiting was assessed in 4 grades as "excellent", "good", "fair" and "poor" based on severity of nausea and number of vomiting that occurred during the first 24hrs after administration of cisplatin. When rescue medication was conducted, the case was assessed as "poor". Ondansetron was significantly superior to placebo in inhibition of nausea and vomiting, in which efficacy rates (excellent+good) of ondansetron and placebo groups were 58.1% (25/43 cases) and 16.7% (7/42 cases), respectively. Number of cases requiring rescue medication with ondansetron injection was obviously greater in placebo group (31 cases) than that in ondansetron group (12 cases). In those patients given ondansetron injection as the rescue medication, satisfactory effects were obtained in 5 cases in ondansetron group and in 18 cases in placebo group. Although side effects including chest itching (ondansetron group), headache and dull headache (placebo group) were observed after the rescue medication with ondansetron injection, these symptoms were not severe and disappeared after 1-2 days. As mentioned above, ondansetron tablet was shown to possess excellent anti-emetic effect on nausea and emesis induced by high dose of cisplatin and to have no problem in safety. Hence ondansetron was proven to be clinically very useful anti-emetic.

Administration, Oral

[Evaluation of SN-307 (ondansetron), given intravenously in the treatment of nausea and vomiting caused by anticancer drugs including cisplatin--a placebo-controlled, double-blind comparative study].

Clinical usefulness of ondansetron as an antiemetic for the treatment of nausea and vomiting induced by anticancer drugs including cisplatin (> or = 50 mg/m2) was evaluated by a multi-institutional, double-blind comparative study with placebo with inpatients with various malignancies. In this study, efficacy, safety and usefulness of single dose of ondansetron (4 mg) or placebo (physiological saline), given intravenously for initial nausea and vomiting were observed for 24 hours after treatment. Clinically, very effective or effective response was seen in 64% (16/25) of the group O (ondansetron) and 5.9% (1/17) of the group P (placebo). No clinically significant adverse effects or abnormal laboratory test values were reported in the group of O. Diarrhea (1 case) and the elevation of laboratory test values (GOT.GPT, T-bilirubin, LDH, in 3 cases) were reported in the group of P. General safety assessment was considered "safe" in 100% of both group O and group P, and there was no statistical difference between two groups. Usefulness was considered as "useful" in 64% (16/25) of group O and 6.3% (1/16) of group P, and O was significantly better than group P (p < 0.001) level. In conclusion, ondansetron provides a safe and effective antiemetic measure when employed therapeutically against nausea and vomiting induced by regimens including cisplatin.

Adult

Free muscle transplantation combined with intercostal nerve crossing for reconstruction of elbow flexion and wrist extension in brachial plexus injuries.

Complete paralysis due to traumatic brachial plexus injury is extremely difficult to treat when the injury affects whole nerve roots and when motor function fails to show any signs of recovery. Seddon has suggested that arthrodesis of the shoulder and amputation at the humerus, combined with the use of a functional upper extremity prosthesis, was the most practical procedure available. Since 1965, in cases of irreparable lesions such as complete root avulsion type injuries, we have performed direct intercostal nerve crossing to the musculocutaneous nerve without free nerve graft to achieve elbow flexion. However, it is necessary to operate on the patient within 6 months following the injury to obtain good results. In the past there was no procedure for dealing with delayed cases of complete brachial plexus palsy. However, with the advent of microsurgical techniques, new approaches have become open to us. Since 1978, we have reconstructed the elbow flexor by the combined surgery of free muscle transplantation with intercostal nerve crossing in delayed cases of complete paralysis. This article introduces the operative technique and the results we have obtained.

Adolescent

Monoclonal antibody against bone marrow stromal cells. Its production and characterization.

Bone marrow stromal cells play an essential role in the proliferation and differentiation of hematopoietic stem cells (1, 2). As a means of analyzing of the bone marrow microenvironment immunohistochemically, we attempted to produce a rat monoclonal antibody against the murine preadipocyte line H-1 derived from long-term bone marrow culture (LTBMC) of C57BL/6 mice (3, 4). A newly established monoclonal antibody, designated R4-A9, was obtained from a hybridoma prepared by fusion of Y.B2/3.0Ag20(YO) rat myeloma cells with spleen cells of LEW rats immunized with H-1 cells. The immunofluorescence of live H-1 cells showed that the antigen reacting with this antibody was strongly expressed on the cell surface. The specificity of R4-A9 was assessed immunohistochemically on frozen sections of various tissues from normal adult mice. R4-A9 demonstrated specificity for hematopoietic stroma in bone marrow and spleen. No staining was observed in thymus, lymph nodes or other tissues examined, with the exception of Leydig cells in the testis and the endothelium of small arteries in several organs. Detailed immunohistochemical observations at both the light microscopy and electron microscopy level showed that R4-A9 selectively reacted with the sinusoidal endothelium, perisinusoidal adventitial cells (5) (adventitial reticular cells (6] and intersinusoidal reticular cells (5) and the reticular cells of the splenic red pulp. These findings indicate that reticular cells and the endothelium of the bone marrow possess the common cell surface molecules recognized by R4-A9. SDS-PAGE analysis showed that R4-A9-immunoprecipitated proteins had a molecular mass of 100 kDa under reducing conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[A case of mesothelioma of perinephric space origin].

Cystic mesothelioma of perinephric retroperitoneum origin are very uncommon tumors and considered potentially malignant. We report one such case and discuss the clinical and pathological findings. A 70-year-old man was seen with complaint of discomfort in the right flank and hospitalized in May 1989. Computerized tomography revealed multiple cystic masses in the right retroperitoneal space which appeared to be infiltrating the kidney and the iliopsoas muscles. Magnetic resonance imaging showed deformation of the right kidney with many impressions in the parenchyma. The cystic lesions and the right kidney were extirpated on June 2, 1989. Grossly the specimen was 16 x 10 x 8 cm in size and 630 g in weight. The multiple cysts surrounding the kidney were each approximately 10 mm in diameter and had thin outer walls. The cyst fluid was clear and serous. The kidney had not been infiltrated but had only external impressions caused by the cystic lesions. Microscopically, the cysts were lined by a single layer of cuboidal cells accompanied by some hobnail-shaped cells, and no evidence of malignancy was found. The epithelium was focally positive for periodate acid Schiff and slightly positive for Alcian blue. It was strongly positive for cytokeratin and vimentin, and slightly positive for EMA but negative for lectins. The diagnosis was diffused benign multicystic mesothelioma. However, CT taken four months after the operation revealed local recurrence and radiotherapy (40 Gy) was instituted. Since the cystic mass tended to grow in size thereafter, the lesion appeared to be malignant clinically. We consider this is the first case of cystic mesothelioma of perinephric retroperitoneum origin reported in Japan.

Aged

[A randomized trial of PVB, VAB-6, BVP regimen versus PEB chemotherapy in patients with disseminated testicular tumors].

During 2 years and 7 months from June, 1985 to December, 1987, a randomized multi-center trial of PVB, VAB-6, BVP regimen (group A) without etoposide versus PEB chemotherapy (bleomycin, etoposide and cisplatinum) (group B) was given to patients with disseminated testicular tumors. Of 34 patients registered, 10 patients were with minimal disease in stages IIA, IIIO and IIIA and 24 with extensive disease in IIB, IIIB2 and IIIC. Seminomas were found in 10 patients, while non-seminomatous tumors in 24. Among groups A and B, there was no statistical difference in clinicopathological profiles. A group patients were given either PVB, VAB-6 or BVP according to the physician's discretion. In groups A and B, 35% and 43% of the patients achieved complete response, and 45% and 50% achieved partial response, respectively. The difference in CR rates among both groups was not statistically significant even when calculated according to the stage or histologic grouping. Salvage treatments mainly with surgical resection of residual tumors after the chemotherapy, however, were more successful in group B (88%) than group A (61%). It appears likely that the higher response of induction chemotherapy in patients with extensive disease made the salvage surgery more successful in group B than in group A. The 3 year survival rate was 100% in group B, whereas it was 76% in group A. Although the incidence of myelosuppression and alopecia was significantly higher in group B, neuropathy was significantly more frequent in group A. From the above results, PEB seems to be a better induction chemotherapy than the conventional one for advanced testicular tumors.

Antineoplastic Combined Chemotherapy Protocols