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Biomedical subjects

Y Akasaka

Publications and source records attributed to Y Akasaka.

At least 55 records · Page 3Linked to original sources

[Chronic eosinophilic pneumonia involving eosinophil cationic protein and bone marrow cells].

A 64-year-old women presented with a dry cough. The common cold was diagnosed and she was given medication, but the symptom did not resolve. She came to our hospital, and multiple patchy shadows were seen on a chest X-ray film. Bronchoalveolar lavage fluid contained an abnormally high percentage of eosinophils. Microscopic examination of transbronchial lung biopsy specimens showed infiltration of eosinophils into the alveoli and alveolar septa. Chronic eosinophilic pneumonia was diagnosed. Analysis of bone marrow cells showed high percentages of mature eosinophilic cells, and blood serum had a high concentration of eosinophil cationic protein. An inhalation challenge test with methacholine revealed bronchial hypersensitivity and hyperresponsiveness. Prednisolone (30 mg/day) was given and the symptoms resolved. After steroid treatment, the patient was asymptomatic, although airway hyperresponsiveness remained. The concentration of eosinophil cationic protein in serum and the results of the methacholine inhalation test reflected the degree of chronic eosinophilic pneumonia, and the production of eosinophils in bone marrow was suppressed by steroid medication.

Blood Proteins↗

A critical mutation in both WT1 alleles is not sufficient to cause Wilms' tumor.

The WT1 gene is a tumor suppressor gene for Wilms' tumor (WT). Inactivation of both alleles has been proposed as the cause of WT. We encountered a patient with Denys-Drash syndrome associated with WT whose WT1 gene had a homozygous point mutation not only in WT but also in renal tissue adjacent to the WT and in the germline. These findings indicate that factor(s) other than the loss of WT1 are required for WT to develop.

Alleles↗

[Pharmacokinetic investigation of 5-day multiple dose of tropisetron capsule in patients who had received cisplatin and the usefulness of tropisetron capsule in the treatment of nausea and vomiting].

We have investigated the pharmacokinetics of a 5-day multiple oral dose of 5 mg tropisetron capsule in patients with malignant tumour who had received cisplatin single administration. Its anti-emetic effects on acute and delayed emesis and vomiting were also investigated. During the 5 days after this administration, changes in the release and metabolism of serotonin were investigated. The results may be summarized as follows: 1) The pharmacokinetic parameters of tropisetron revealed no significant change in the data between day 1 and day 5. Also, the parameters were almost similar to those observed in healthy adult males (clinical phase I study); Cmax. T1/2 and AUC 0-24 hrs on day 1 were 9.1 +/- 2.1 ng/ml, 12.5 +/- 4.2 hrs, 85.5 +/- 22.7 ng.hr/ml, respectively. The urinary excretion of the parent drug up until 24 hours after administration on day 1 was 3.8% of the dose administered and 2.9% of the total dose after the last administration; no difference in the urinary excretion rate was observed in healthy subjects. It was thus suggested that hydration accompanied by cisplatin administration did not affect the pharmacokinetics of tropisetron. 2) The changes in the amount of urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA) during 5 days after cisplatin administration were observed; urinary excretion of 5-HIAA increased 2.3 times (1.3-5.4 times) the baseline on the average during 6 to 12 hours on day 1. In 6 out of 10 patients, the increases in urinary excretion of 5-HIAA showed double or more the baseline during 2 to 5 days after cisplatin administration. Serotonin was thus deemed to be related to the development of delayed emesis. 3) The anti-emetic effects of tropisetron on acute and delayed emesis and vomiting were rated as "markedly effective" in 6 out of 11 patients (54.6%) and "effective" in 1 out of 11 patients (9.1%) on day 1; vomiting did not occur in any of these 7 patients. Tropisetron also controlled emesis and vomiting during days 2-5, and was rated as "almost favorable" in 6 out of 11 patients (54.5%). Further, in 4 out of 6 patients, in whom the urinary excretion of 5-HIAA was increased on day 2 onwards, vomiting did not occur during the time when the urinary excretion of 5-HIAA was increasing. On the basis of the above results, tropisetron is deemed to have certain antiemetic effects on delayed vomiting as well. Its 5-HT3 receptor mediated mechanism was similarly seen to inhibit acute nausea and vomiting.

Adult↗

[Two case reports of retroperitoneal leiomyosarcoma].

Two cases of retroperitoneal leiomyosarcoma are presented. The first case was in a 67-year-old female, whose chief complaint of right upper abdominal mass and dull pain. The tumor, 13 x 12 x 8 cm in size, developing in the retroperitoneum was removed with the right kidney and vena cava. The pathological diagnosis was reported as leiomyosarcoma. The second case was in a 62-year-old male, whose complaint was left abdominal swelling, also with general fatigue. A large tumor mass, invading over all of the left flank organs, was palpable by physical examinations, from which the mass was far beyond surgical approach. Needle biopsy revealed the pathological finding of leiomyosarcoma. One month later, the patient died of cachexia. Review of the literatures for the retroperitoneal leiomyosarcoma, revealed only a few cases; 1.7%, of all leiomyosarcoma to date.

Aged↗

[The antiemetic effect, safety and usefulness of tropisetron capsule in the treatment of nausea and vomiting induced by lower multiple dose of cisplatin].

The antiemetic effect, safety and usefulness of once daily administration of tropisetron 5 mg capsule for 3 to 5 consecutive days was investigated in 37 cases of 12 stations in total, suffering from nausea and vomiting induced by a lower multiple dose of cisplatin. The efficacy ratings assessed every 24 hours on day 1, 2, 3, 4 and 5 were 88.6%, 85.7%, 82.9%, 74.1% and 76.9%, respectively. The final efficacy rating was 82.9% (29/35 cases). Although no adverse event was observed, increases in GOT and GPT, whose cause and relation to the investigational drug were unknown, were noted in 2 cases. Cases rated as useful or better were 82.9% (29/35 cases) of the overall. The above results reveal that tropisetron 5 mg capsule is significantly effective and highly safe in the treatment of nausea and vomiting induced by lower multiple dose of cisplatin. Tropisetron 5 mg capsule is thus deemed extremely useful antiemetic drug.

Antiemetics↗

[Clinical phase II study of tropisetron capsule in the treatment of nausea and vomiting induced by anti-cancer drugs].

A comparative clinical trial of tropisetron capsule was conducted in three dose groups to investigate its optimal dose on nausea and vomiting induced by anti-cancer drugs, including cisplatin. The doses were randomized by the central registration office. In the assessment of clinical efficacy, cases rated as "effective" or better accounted for 61.5% of the 2.5 mg group (16/26), 80.8% of the 5.0mg group (21/26) and 80.0% of the 10mg group (24/30), respectively; the ratings for the 5mg and 10mg groups were almost equivalent, which was higher than that for the 2.5mg group. Adverse events observed were fever, diarrhea, drowsiness, headache and/or facial erythema in 4 out of 97 cases. Abnormal laboratory findings noted were 6 cases of increased GOT, GPT, LDH, total bilirubin and/or creatinine, but none of these was serious or clinically problematic in particular. On the basis of the above results, the optimal dose of Tropisetron (capsule) is considered to be 5mg once daily.

Adult↗

[Clinical phase III study of tropisetron capsule in the treatment of nausea and vomiting induced by anti-cancer drug; a placebo-controlled, multicenter, double-blind comparative study].

A placebo-controlled, double-blind comparative study of tropisetron capsule was conducted to assess its clinical usefulness for nausea and vomiting induced by the anticancer drug, cisplatin, at a single dose of 50 mg/m2 or higher. Either 5mg tropisetron capsule or its placebo was given orally to patients 2 hours prior to cisplatin administration; the clinical efficacy was determined the severity of nausea and the number of emesis that occurred during 24 hours after cisplatin. Tropisetron significantly exceeded the placebo in the assessment of clinical efficacy. The ratings for the tropisetron group and the placebo group were 91.7% (22/24 cases) and 25.9% (7/27 cases), respectively. Adverse events observed were one case of headache in the tropisetron group and one diarrhea in the placebo group, while neither case was serious nor clinically problematic in particular. The above results reveal that tropisetron 5 mg capsule is significantly effective in the treatment of anticancer drug-induced nausea and vomiting. It has also been confirmed that tropisetron is a useful agent without any safety problems.

Administration, Oral↗

[Clinical phase III study of tropisetron capsule in the treatment of nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs].

A clinical phase III study of tropisetron capsule was conducted to assess its efficacy, safety and usefulness on nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs. The study was conducted in patients who experienced vomiting on previous chemotherapy. Tropisetron 5 mg capsule was given to patients once 2 hours prior to the first administration of either carboplatin or non-platinum anti-cancer drugs; the patients were then observed for nausea and/or vomiting during 24 hours after the first administration. Some 56.7% (17/30) of the patients did not vomit after tropisetron administration, and the frequency of vomiting was significantly reduced compared with that during the previous chemotherapy. Further, in the clinical efficacy ratings, in which the efficacy was assessed on the basis of the nausea and vomiting data, 83.3% (25/30) of cases were rated as "effective or better". Adverse events observed were 3 cases of mild headache, but these were not clinically problematic. The above results reveal that tropisetron capsule is significantly effective and safe in the treatment of nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs; in addition, tropisetron proved to be highly useful for its convenience as an oral agent.

Adult↗

[Clear skeletal visualization on whole body 201Tl-chloride scintigraphy: a case of prostatic cancer with diffuse bone metastases].

A 70-yr-old man who was diagnosed as early gastric cancer showed leukocytopenia after total gastrectomy. Osteosclerotic findings on radiography were not remarkable. 99mTc-HMDP bone scintigraphy showed diffusely increased uptake in the axial skeleton, but visualization of the kidney and urinary bladder was apparent. However, whole body 201Tl-chloride scintigraphy showed diffuse abnormal visualization of axial skeleton. Physical and ultrasonographic examination indicated no abnormality in prostate. Afterward, further investigation, including bone marrow biopsy and immunohistochemical study, confirmed the diagnosis of bone metastasis from prostatic cancer. Microscopically, metastatic tumor cells were located in the intertrabecular space. Furthermore, no osteoclastic bone resorption or new trabecular bone formation was seen in this biopsy specimen. These findings suggest that whole body 201Tl-chloride scintigraphy can be a useful non-invasive diagnostic tool to investigate patients with suspicious malignancy in the bone marrow.

Adenocarcinoma↗

[Clinical study of the advanced testicular tumor non-achieved complete response by primary chemotherapy and relapse cases. The East Japan Testicular Tumor Study Group].

The East Japan Testicular Tumor Study group has studied advanced testicular tumors. Treatment and prognosis of the patients who did not achieved complete response on the primary chemotherapy were discussed in this paper. Also 8 patients who had once reached complete response by primary treatments and relapsed later have been clinically analyzed. 1. Concerning the patients non-achieving complete response on the primary chemotherapy: Two cases who had resection of the residual tumors and 4 cases who had radiation therapy had reached NED in 7 cases of seminoma stage II. Nine of 10 cases in non-seminoma stage II reached NED on resection of the residuals. Moreover, 10 out of 17 cases in stage III showed NED on excision of the residuals. On the other hand, recuperating was very difficult in the cases who could not have excision of residual tumor. The histological findings of the residual tumors after chemotherapy were necrosis and fibrosis in 13 cases, viable cells in 4 cases, teratoma in 6 cases and other 2 cases were not clear. Five out of 15 who had teratoma in the primary lesion had teratoma in the resected residuals on metastatic lesion. On the other hand 5 patients who did not have teratoma originally had no any teratoma elements in the residuals. 2. Concerning the relapse cases by primary treatments: Although relapses were possible in any stages, they were more common with stage IIIB and IIIC cases. Those who achieved complete response after chemotherapy alone fewer relapse than those who had partial response after chemotherapy and there after had excision of residual tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy↗

A point mutation found in the WT1 gene in a sporadic Wilms' tumor without genitourinary abnormalities is identical with the most frequent point mutation in Denys-Drash syndrome.

We have analyzed exon 9 of the WT1 gene of 18 non-familial/sporadic unilateral Wilms' tumors (WTs) from Japanese patients, by the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method. After screening these WTs, a nucleotide alternation, which was present on both alleles, was found in only one case. Furthermore, PCR-SSCP analysis of the constitutional DNA revealed that this patient carried the mutation on only one allele in the germline. Sequence analysis showed that the tumor carried a point mutation (C-1180 to T-1180) in WT1 exon 9 of both alleles, resulting in an Arg-394 to Trp-394 amino acid substitution within the third zinc finger domain of the WT1 product. Interestingly, this mutation is identical with the most frequent point mutation associated with the Denys-Drash syndrome. However, the classical triad of Denys-Drash syndrome does not apply to this patient. This is in the first report of the point mutation in the zinc finger domain of both WT1 alleles in a sporadic unilateral WT without genitourinary abnormalities, and the mutation suggests that some sporadic WTs carry the Denys-Drash WT1 mutations.

Base Sequence↗

Fatal herpes simplex hepatitis type 2 in a post-thymectomized adult.

The authors report an unusual case of herpes simplex type 2 (HSV) hepatitis which presented as part of a systemic HSV infection accompanied by disseminated intravascular coagulation (DIC). The patient was a 49-year-old Japanese male who three months prior to admission underwent surgical resection of his thymus for an invasive thymoma. Postoperatively, he received a course of chemotherapy which included prednisone, cyclophosphamide, vincristine, and pinorubicin. After discharge from the hospital, he was put on a maintenance dosage of prednisone and cyclophosphamide. Two weeks prior to this admission, the patient developed rhinorrhea, chills and general fatigue. Routine follow-up laboratory tests revealed markedly elevated liver enzymes which led to his immediate hospitalization. The tentative diagnosis on admission was fulminant hepatitis with DIC. The patient's condition steadily worsened during his hospitalization and acyclovir was initiated on the 4th hospital day due to the possibility of HSV hepatitis. He died on the same day. Histopathology performed on the liver at autopsy revealed hepatic inclusion bodies of HSV with positive immunohistochemical detection of the HSV type 2 antigen. Our case is the first report of HSV hepatitis associated with the removal of the thymus secondary to thymoma. It supports previous observations of disseminated HSV infection being prevalent in those patients with disorders of cell mediated immunity.

Antineoplastic Combined Chemotherapy Protocols↗

Primary embryonal carcinoma of the retroperitoneum.

A 32-year-old man with primary embryonal carcinoma of the retroperitoneum, a very rare condition, is reported. The disease took an acute course with rapid enlargement of cervical and inguinal lymph nodes, and high serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) values were observed. His testes were, however, intact. Remarkable tumor regression was achieved by systemic combination chemotherapy with cisplatin, vinblastine, and bleomycin (PVB therapy). This chemotherapy is beneficial even in advanced cases. In the two years since therapy, no recurrence has been observed.

Adult↗

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↗