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Biomedical subjects

T Shitara

Publications and source records attributed to T Shitara.

At least 55 records · Page 3Linked to original sources

Dipyridamole enhancement of drug sensitivity in acute lymphoblastic leukemia cells.

The effect of dipyridamole (DPM) on cell sensitivity to anticancer drugs was examined in acute lymphoblastic leukemia (ALL) cell lines. We established two ALL cell lines (KMO-90 and KMO-R) from bone marrow samples of a 12-year-old girl with ALL. The drug concentrations needed to reduce optical density to 50% of that of control cells (IC50) showed that KMO-R was about twofold more resistant to doxorubicin (DOX), mitoxantrone (MIT), vincristine (VCR), and etoposide (VP-16) than was KMO-90. Considering that both KMO-90 and KMO-R were established from a patient with ALL at the time of presentation and relapse, respectively, these two cell lines might be novel and useful models for research into the acquisition of drug resistance in ALL cells. Although cytotoxicity of DPM in KMO-90 was about 6% at 1 microgram/ml, DPM enhanced cell sensitivity to DOX, MIT, VCR, and VP-16 at this concentration. Cytotoxicity of DPM in KMO-R was less than 5% at 1, 5, and 10 micrograms/ml. In KMO-R, DPM enhanced cell sensitivity to these four drugs in a dose-dependent manner. The plasma concentrations achieved by oral administration of DPM is about 1 microgram/ml. At clinically achievable concentrations, DPM enhanced cell sensitivity to DOX, MIT, VCR, and VP-16 in both KMO-90 and KMO-R, thus showing DPM to be a useful agent for potentiating anticancer chemotherapy of hematopoietic malignancy.

Administration, Oral↗

Infrequent involvement of p53 mutations and loss of heterozygosity of 17p in the tumorigenesis of renal cell carcinoma.

Restriction fragment length polymorphism (RFLP) analysis and the polymerase chain reaction of the single-strand conformation polymorphism (PCR-SSCP) method were conducted to assess the loss of heterozygosity of chromosome 17p and mutations of the p53 gene in 30 surgical specimens of human renal cell carcinoma. Six of 29 tumors (20.6%) showed loss of heterozygosity on chromosome 17p in RFLP analysis, and in none of 21 tumors could a mutation be found on exons 5 to 8 of the p53 gene in PCR-SSCP analysis. We conclude that the p53 gene mutation does not play a role in the development of the majority of cases of renal cell carcinoma and that there may be another tumor suppressor gene on 17p.

Carcinoma, Renal Cell↗

Infrequent involvement of p53 gene mutations in the tumourigenesis of Japanese prostate cancer.

A study was made of the incidence of p53 mutations in Japanese males with prostate cancer or benign prostatic hyperplasia. Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) was used as a primary screening technique with gene sequencing being carried out in positive cases. Two out of 21 prostate cancers (9.5%) were found to have p53 mutations. These were stage B2 and D2 prostate cancers. No abnormalities were found in the remaining cases or benign prostatic hyperplasia. Mutations of the p53 gene would thus appear infrequent in the tumourigenesis of primary prostate cancer.

Adenocarcinoma↗

[Cholesteatoma in children--sex differences].

It has been reported that cholesteatoma is more aggressive in children than in adults and that it affects boys more often than girls. We found particularly prominent sex differences in the clinical characteristics and behavior of cholesteatoma in children, by comparing them with those of acute otitis media (AOM), otitis media with effusion (OME) and adult cholesteatoma. We retrospectively analyzed the clinical records of children diagnosed as having cholesteatoma by comparing their courses with those of AOM, OME, chronic otitis media, microtia and congenital malformation of the ossicles. The boy-dominant tendency were observed in OMA, OME, pediatric cholesteatoma, microtia and congenital malformation of the ossicles. Cholesteatoma has a tendency to fill the middle ear cleft in boys, in whom the most extensive cholesteatomas were observed. If OMA, OME, and cholesteatoma in children are considered to be a series of inflammatory middle ear diseases, a common factor must be involved in the boy-dominant tendency for this series of inflammatory middle ear diseases. We have proposed six factors contributing to sex differences in pediatric cholesteatoma. Among these, immunological, environmental and congenital factors were thought to be responsible for the sex differences.

Acute Disease↗

[Idiopathic bilateral sensorineural hearing loss: clinical study of cases with rapidly progressed deafness].

In a series of 127 patients with idiopathic bilateral sensorineural hearing loss (IBSH) at the Hearing Clinic in the Department of Otolaryngology, Kitasato University Hospital, 20 cases showed rapid progression of hearing impairment. These patients had been treated with the same therapeutic regimen used in sudden deafness (S.D.). Improvement of hearing loss after treatment was generally less effective in the cases with rapidly progressed IBSH than in the cases with S.D. However, hearing improvement was achieved in some cases with rapidly progressed IBSH when the treatment had started in the early stages after the onset of rapidly progressive hearing loss. The mode of fluctuating hearing loss in the cases with rapidly progressed deafness was assumed to be similar to that in the group of all cases with IBSH.

Adolescent↗

Establishment of a new human pre-B acute lymphoblastic leukemia cell line (KMO-90) with 1;19 translocation carrying p53 gene alterations.

A new human pre-B acute lymphoblastic leukemia cell line (KMO-90) was established from the bone marrow sample of a 12-year-old girl with acute lymphoblastic leukemia (ALL) carrying 1;19 chromosome translocation. KMO-90 cells expressed HLA-DR, CD10, CD19, and CD22 antigens. These cells had also cytoplasmic immunoglobulin lacking surface immunoglobulin, indicating that these had a pre-B phenotype. Chromosome analysis of this cell line showed 48, XX, +8, +19, t(1;19)(q23;p13). Southern blot analysis showed the same sized rearrangements of the E2A gene in KMO-90 cells as those in the original leukemic cells. By means of reverse transcriptase-polymerase chain reaction analysis, we detected E2A/PBX1 fusion transcripts in KMO-90 cells. KMO-90 is useful when studying the role of the 1;19 translocation in the etiology of pre-B ALL. Furthermore, we studied alterations of the p53 gene in this cell line by polymerase chain reaction, single-strand conformation polymorphism analysis. KMO-90 cells were identified to have a point mutation at codon 177 (CCC-->TCC) of the p53 gene, suggesting that alterations of the p53 gene may have an important role in the establishment of this cell line.

Antigens, Surface↗

Treatment of standard risk acute lymphoblastic leukemia in children with the Tokyo Children Cancer Study Group (TCCSG) L84-11 protocol in Japan.

During the period June 1984 through February 1989, 207 children, newly diagnosed with standard-risk acute lymphoblastic leukemia (ALL), were treated with the Tokyo Children Cancer Study Group L84-11 protocol. The patients were randomized into two regimen groups (S1 and S2). All patients received identical induction therapy with vincristine, prednisolone, and L-asparaginase. For central nervous system (CNS) prophylaxis, the patients in regimen S1 received cranial irradiation (18 Gy) and intrathecal chemotherapy starting at 5 weeks, while those in regimen S2 received this therapy starting at 24 weeks. Consolidation consisted of cyclic therapy with vincristine and dexamethasone, and then, after 128 weeks, with medium-dose methotrexate, CNS chemoprophylaxis, and dexamethasone. Regimen S2 employed early consolidation with three doses of medium-dose methotrexate and CNS chemoprophylaxis. The treatment duration was 3.5 years. Complete remission was achieved in 96.0% and 99.0% of the patients in regimens S1 and S2, respectively. Event-free survival (EFS) rates were 80.0 +/- 3.5% in total, 74.5 +/- 5.7% in regimen S1, and 85.1 +/- 5.7% in regimen S2 at a median follow-up of 42 months (< 85 months). There was no significant difference in the EFS between the two regimens. As compared with recently reported results of treatment for this disease, our protocol can yield similar EFS rates with mild toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Synthesis of 5-deoxy-5-fluoro and 5-deoxy-5,5-difluoro derivatives of kanamycin B and its analogs. Study on structure-toxicity relationships.

5-Deoxy-5-fluoro- (1), 5.3'-dideoxy-5-fluoro- (2), and 5,3',4'-trideoxy-5-fluoro-kanamycin B (3) have been prepared by treatment of 5-epihydroxyl precursors (prepared by the Mitsunobu reaction) with DAST as the key step. 5,3'-Dideoxy-5,5-difluoro- (26) and 5,3',4'-trideoxy-5,5-difluoro-kanamycin B (27) were also prepared by treatment of the corresponding 5-oxo derivatives with DAST. These 5-deoxy-5-fluoro and 5-deoxy-5,5-difluoro derivatives showed markedly decreased toxicity as compared with the parent compounds.

Carbohydrate Sequence↗

A case of congenital leukemia with monosomy 7.

A case of congenital leukemia with monosomy 7 is reported. Immunological study of the blast cells using monoclonal antibodies was suggestive of both myelomegakaryocytic and T-lymphoblastic leukemia. Chromosomal analysis of the bone marrow cells showed monosomy 7. Chemotherapy was initiated with a combination of adriamycin, cytosine arabinoside, 6-mercaptopurine, and prednisolone. The patient obtained complete remission, which has been maintained for 4 years and 1 month. He receives no chemotherapy now. Our case shows that monosomy 7 in congenital leukemia is rare, but the presence of monosomy 7 in congenital leukemia does not necessarily indicate a poor prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

Reversal of the malignant phenotype by an anti-ras ribozyme.

In this study a ribozyme (catalytic RNA) was designed to site specifically cleave the mRNA of the activated H-ras gene expressed in human bladder carcinoma EJ cells. The optimal conditions for catalytic cleavage by the ribozyme were demonstrated in vitro. A synthetic DNA encoding the ribozyme was cloned into a mammalian expression vector (pH beta APr-1) and transfected into EJ cells. The expressed ribozyme significantly altered the morphology and suppressed the growth of EJ cells in vitro. These cell lines were examined for their malignant potential in athymic (nude) mice by an orthotopic (transurethral) implantation model, which recapitulates the invasive potential of various bladder carcinomas. EJ tumors expressing the H-ras ribozyme were characterized by a marked reduction in tumor take and invasion compared to those formed by control EJ cells. These differences resulted in almost a twofold increase in survival of mice implanted with ribozyme-containing EJ cells. These results further elucidate the role of ras genes in tumorigenicity and invasion, as well as introduce ribozymes as a new class of anticancer agents.

Animals↗

[The effect of aging on observation in hearing in the same individuals over a 5 year period].

The purpose of this study was to investigate the process of changes in hearing of pure tones with aging. Among individuals who had undergone thorough medical examination for the purpose of annual health-checks, 293 males (586 ears) whose hearing level had been examined for five years or more were enrolled in this study. Cases having conductive deafness or known sensori-neural deafness were excluded. Since the most typical change with aging is observed at 8 kHz, the investigation was carried out only on hearing at 8 kHz. Hearing level increasingly declined with advancing age. Hearing distribution for young subjects showed a peak in the normal hearing level range. This peak decreased with aging, and another peak appeared at 50 dB. Investigation of differences in hearing in the individuals over the five years showed that most subjects had a hearing level difference of 0 dB up to 54 years of age. From 55 years old onward, however, the difference was 5 dB. This indicates that gradual deterioration of hearing level with aging occurs most frequently. On the other hand, in some subjects, deafness progressed faster. Thirty-four and a half percent of the subjects had deteriorations of 20 dB or more in a single year during the entire observation period. A deterioration of 20 dB or more was noted in 4% of the young and 8% of the elderly. Such rapid progression of deafness was believed to be involved in formation of the 50 dB peak in the hearing distribution.

Adult↗

Erythroleukemia in a child associated with monosomy 7.

A case of erythroleukemia (EL) associated with monosomy 7 is reported. The EL was diagnosed 20 months after the initial diagnosis of monosomy 7 was made. An immunologic study of the blast cells using a monoclonal antibody was positive for glycophorin A, which suggested that they were of erythroid origin; this was confirmed by electron microscopy. Chemotherapy was started with low dose cytarabine. However, the patient had severe bone marrow suppression and died of pneumonia. Our case shows that monosomy 7 is an abnormality of the pluripotential stem cells, including erythroid cells, that resulted in a true erythroid neoplasm.

Child, Preschool↗

[Primary carcinoid tumor of the testis with metastasis to the upper vertebrae. Report of a case].

A case of primary carcinoid tumor of the right testis with metastases to the cervical and thoracic vertebrae and epidural is reported. A 53-year-old man was first recognized as being with dysthesia of the left arm and shoulder in April 1986. In June, 1987, he was admitted to the Neurology service, complaining of sudden occurrence of abasia. Myelography and computerized tomography demonstrated an epidural mass and several high density areas in the vertebral bodies of Th1 and Th2. The patient underwent laminectomy from C7 to Th2. At operation, the neurosurgeons noticed a tumor mass in the right scrotum and requested our consultation. Thus right high orchiectomy was performed. Pathological examination including Grimerius' and Fontana-Masson's stain revealed carcinoid tumor of the right testis associated with metastases to the spinal column. Postoperatively, tumor maker studies revealed elevation of blood 5-hydroxytryptophan and marked increase of urinary 5-hydroxy-indoleacetic acid excretion. They showed remarkable decreases after a course of PVB chemotherapy. The patient has been under our observation as an out-patient for the past 27 months with metastases. This is the first case of primary carcinoid tumor of the testis with metastases so far reported in the domestic literature.

Carcinoid Tumor↗

[Incidental renal cell carcinoma].

We reviewed the cases of incidental renal cell carcinoma that had been treated at the Kitasato University Hospital between July, 1971 and December, 1989. Forty one of the 170 (24.1%) cases were found without any direct signs of renal cell carcinoma. The patients were between 30 and 78 years old (mean 55.0 years) and consisted of 29 males and 12 females. Fifteen cases were detected at the general health check-up and the remaining 26 during the postoperative follow-up for other malignant tumors or other diseases. Twenty three cases were identified by ultrasonography followed by computed tomography (CT) and excretory pyelography in 4 cases each. Especially, the number of patients incidentally found by ultrasonography had increased in the recent 8 years. Urinalysis did not show any microhematuria in 31 of the 37 cases (83.7%), and no tumor mass could be detected by excretory pyelography in 3 cases. We believe that ultrasonography may be valuable as a screening modality for early detection of renal cell carcinoma and should be used as a screening method at the routine health check-up.

Adult↗