Search PubMed⌕ Search

Biomedical subjects

M Wada

Publications and source records attributed to M Wada.

At least 361 records · Page 20Linked to original sources

[Occurrence of ileus after voglibose treatment in an elderly diabetic patient with gait disturbance caused by cerebral hemorrhage].

Alpha-glucosidase inhibitor can suppress postprandial hyperglycemia by delaying the absorption of carbohydrates in the intestine, and may be useful in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and preserved insulin secretion. We encountered an obese elderly patient with NIDDM in whom gait disturbance had developed after cerebral hemorrhage and who suffered from ileus after treatment with voglibose. The patient had received voglibose which is reported to cause fewer abdominal symptoms than acarbose, for 15 days. The patient, a 63-year-old woman, was given a diagnosis of NIDDM in February 1995, and was treated with a sulfonylurea agent. However, her glycemic control remained poor and she was admitted to our hospital in April 1995. Her body mass index was 30.5 kg/m2 and laboratory investigation revealed a fasting plasma glucose level of 211 mg/dl, a postprandial (2 h) plasma glucose level of 288 mg/dl, HbAlc of 9.9%, a fasting insulin level of 9 microU/ml, urinary C-peptide excretion of 95.7 micrograms/ day, and an coefficient of variation of R-R value of 2.1%. Fifteen days after glibenclamide was replaced by to voglibose, abdominal pain, nausea, constipation, and ausculatory sounds of gurgling developed, and niveau were noted on an abdominal roentgenogram which indicated that simple ileus had developed. Voglibose was discontinued and the patient was treated with an enema and hot air. She recovered from simple ileus on the next day. This patient had had two abdominal surgeries and a cerebral hemorrhage, and her daily physical activities were limited, which might have contributed to ileus. In elderly patients with NIDDM, a history of abdominal surgery and the amount of daily exercise must be considered when deciding whether or not to give alpha-glucosidase inhibitors.

Cerebral Hemorrhage↗

Effects of dietary n-3/n-6 and polyunsaturated fatty acid/saturated fatty acid ratios on platelet aggregation and lipid metabolism in rats.

We studied the effects of dietary lipids on platelet aggregation and lipid metabolism in rats by varying the n-3/n-6 ration while maintaining the polyunsaturated fatty acid/saturated fatty acid (P/S) ratio fixed, and vice versa. After two weeks, the platelet counts decreased as the dietary n-3/n-6 ratio rose, and platelet aggregation was sufficiently suppressed at the ratio of 0.2. Differences in the dietary P/S ratio, however, did not affect either the platelet counts nor platelet aggregation. As the dietary n-3/n-6 ratio rose, the proportion of arachidonic acid (AA) in the plasma and the phospholipids (PL) of the platelets and aorta decreased gradually, whereas the proportion of eicosapentaenoic acid (EPA) in each tissue increased gradually. The proportion of EPA was higher in the platelets than in the aorta, while that of docosahexaenoic acid (DHA) was higher in the latter. The production of platelet thromboxane A2 (TXA2) and aortic prostacyclin (PGI2) showed sharp declines, from the values for the n-3/n-6 ratio of 0.02 (control) to those for 0.5. These results suggest that the n-3/n-6 ratio of dietary fats necessary to ensure the suppression of platelet aggregation in normal rats would be at least 0.2 and no more than 0.5.

Animals↗

[The relation of age, gender and sex-role identity to role expectation in same-sex friends].

The purpose of this study was to examine the relation of age, gender, and sex-role identity to role expectation in same-sex friends (SSF). Role expectation in SSF consisted of ten categories (Wada, 1993): Cooperation, information, similarity, self-enhancement, sensitivity, companionship, authenticity, self-disclosure, respect, and interdependence. Subjects were 129 (67 male and 62 female) junior high school, 243 (118 male and 125 female) senior high school, and 168 (88 male and 80 female) college students. Major findings were as follows: Senior high school and undergraduate students expected more self-enhancement from SSF than junior high students. Junior and senior high school students expected more companionship than undergraduates. Undergraduates expected more authenticity and less self-disclosure than junior high school students. And male students expected more companionship, information, and similarity, but less self-disclosure, self-enhancement, and respect from SSF than female. Clear results of the relationship between sex-role identity and role expectation in SSF weren't found.

Adolescent↗

[Carotid screening with duplex scanning before coronary artery bypass].

Seventy-one patients undergoing scheduled coronary artery bypass were preoperatively evaluated for the presence of carotid stenosis by duplex scanning. Prevalence of a moderate degree of stenosis (peak systolic flow velocity of internal carotid artery > 130 cm/sec) or a high degree of stenosis (peak systolic flow velocity > 250 or < 25 cm/sec) was 12.7% (nine patients). Predictive risk factors for carotid stenosis were diabetes mellitus and history of stroke. Compared with carotid angiogram, hemodynamically critical stenosis greater than 90% was found in three patients, severe stenosis (75-90%) in four, moderate stenosis (50-75%) in two. Bilateral carotid occlusion, complete occlusion of an internal carotid artery with contralateral 99% stenosis, was found in one patient. In the critical stenosis group (n = 3), simultaneous carotid endarterectomy and coronary artery bypass were performed in two and coronary artery bypass alone in one patient with unilateral complete occlusion of the internal carotid artery. There was neither operative death nor postoperative stroke in this series of patients. In conclusion, carotid screening with a duplex scan is very helpful to evaluate the presence of carotid occlusive disease in coronary artery bypass candidates. When significant carotid stenosis is detected, further examination should be done to clarify the carotid hemodynamics and brain protection during the operation should be employed.

Adult↗

Augmentation of epirubicin cytotoxicity by cycloheximide.

The effect of cycloheximide (CH) on the cytotoxic activity of the anthracycline antibiotic epirubicin (EPI) was examined in cell cultures of murine leukemia doxorubicin (DOX)-sensitive P388 and -resistant P388 cells. The addition of CH (0.002 mu g/ml) to the growth medium markedly enhanced the EPI-induced cytotoxic effect in sensitive cells as well as that observed in resistant cells. CH, however, did not affect the intracellular content of EPI. The inhibition of DNA synthesis in leukemia cells was remarkable with the combination of EPI and CH compared with each drug alone. These results suggest that the combination of EPI and CH appears to be useful in killing mouse leukemia cells.

Animals↗

[FLAIR images of patients with head injuries].

FLAIR (fluid-attenuated inversion recovery) images are MR images obtained with an inversion recovery sequence, which has a long inversion time (TI) and a long echo time (TE). We examined 29 cases (49 graphics) of cerebral contusion, 11 cases (22 graphics) of diffuse axonal injury (DAI) and 11 cases (11 graphics) of traumatic subarachnoid hemorrhage (t-SAH) with FLAIR sequence consisting of a repetitive time (TR) of 6500 msec, TI of 1700 msec and TE of 110 msec, and these graphics were compared with T2-weighted images by spin-echo sequence (TR 2500 msec, TE 90 msec) and computed tomographic (CT) scans. Some lesions of DAI were demonstrated more clearly with FLAIR images than with conventional T2-weighted images. Although contusion could be detected with FLAIR images as well as with conventional T2-weighted images, lesions adjacent to cerebral sulci were better delineated with FLAIR images. Because the cerebrospinal fluid signals in cerebral sulci were low-intensity, FLAIR images were useful in detecting lesions of the cerebral cortex adjacent to cerebral sulci. Although it has been reported that detection of SAH is difficult with standard T1- and T2-weighted images, the presence of t-SAH could be confirmed with FLAIR images as seen in CT scans.

Adult↗

[FLAIR images of cerebral and brain stem infarction].

FLAIR (fluid-attenuated inversion recovery) images are MR images obtained with an inversion recovery sequence having a long inversion time (TI) and a long echo time (TE). We examined 47 cases (56 graphics) of lacunar infarction (LI), 28 cases (32 graphics) of cortical infarction (CI) and 16 cases (23 graphics) of stem infarction (SI) with a FLAIR sequence having a repetitive time (TR) of 6500 msec, a TI of 1700 msec and a TE of 110 msec, and compared these graphics with T2-weighted images by spin-echo sequence (TR 2500 msec, TE 90 msec). LI and CI were better demonstrated with FLAIR images than with conventional T2-weighted images. FLAIR images were very useful in detecting lesions adjacent to the lateral ventricles and the cerebral sulci in particular, because the cerebrospinal fluid signals in the lateral ventricles and the cerebral sulci were low-intensity, with brain tissue appearing as high-intensity areas. In a number of old infarctions, FLAIR images revealed cystic structures, constructed out of internal low-intensity areas and peripheral high-intensity areas. These structural changes suggested that FLAIR images can provide information on pathological changes.

Aged↗

Recovery of interphase nuclei from extreme structural alterations in centrifuged fern protonemal cells.

Nuclear ability to recover morphologically and physiologically from tremendous elongation induced by centrifugation was investigated in single-celled protonemata of the fern Adiantum capillus-veneris. Basipetal centrifugation at a strength of ca. 2000 g for more than 1 h caused an extremely long (more than 500 microns), thread-like chromatin-containing extension of the nuclear envelope in the centrifugal direction. The nucleolus was either located inside a terminal widening of the extension, or it was detached from the thread and located outside the nucleus. Such enucleolation occurred in about half of the nuclei during 3 h of basipetal centrifugation. After centrifugation, the nuclei recovered morphologically by completely reducing the chromatin thread. One day after the end of centrifugation, all nuclei again contained a nucleolus, indicating that nucleolar regeneration had taken place in the interphase nucleus. Almost all basipetally centrifuged cells were still able to divide under white light conditions. A strong delay in the division time course may be attributed to recovery processes of the nuclear internal order. The remarkable ability of the Adiantum interphase nuclei to recover morphologically and physiologically is assumed to be due to processes which also drive the maintenance of the functional nuclear structure during interphase.

Cell Fractionation↗

[Polycythemia vera progressing to acute lymphoblastic leukemia after 13 years].

A 54-year-old woman with leukocytosis, was referred to our clinic in February 1982. Based on findings of pancytosis, high NAP score, high serum vitamin B12, increase in total red cell volume and splenomegaly, she was diagnosed as having polycythemia vera (PV). Since then, she has been treated with pipobroman, hydroxycarbamide and phlebotomy. Leukocytosis with increase in blastic cells and thrombocytopenia was noted in August 1995, and she was admitted to our hospital. Since the blastic cells were CD10(+)19(+)20(+), she was diagnosed as having acute lymphoblastic leukemia and treated with vincristine and prednisolone, resulting in remission. This case suggests that PV is a disease of multipotent stem cells including those with a lymphoid lineage.

Antineoplastic Combined Chemotherapy Protocols↗

Detection of heparan sulfate in spinal spheroids of beta, beta'-iminodipropionitrile (IDPN)-treated rats.

Beta,beta'-Iminodipropionitrile (IDPN) is known to produce a massive accumulation of neurofilaments in the proximal portion of axons of spinal anterior horn cells. The spinal cords of 20 Wistar rats treated with IDPN were examined immunohistochemically with a monoclonal antibody against heparan sulfate (HepSS-1). Virtually all axonal swellings were intensely labeled with HepSS-1. This immunoreactivity was almost completely absorbed by the presence of CDSNS-HS (completely desulfated, N-sulfated heparan sulfate). Western blot study revealed that HepSS-1 recognized four distinct bands at the positions of approximately 17 kDa, approximately 20 kDa, approximately 21 kDa, and approximately 25 kDa. The present study suggests that the deposit of heparan sulfate in spheroids is related to the pathomechanism for the formation of axonal swelling.

Animals↗

Allelotype analysis of childhood acute lymphoblastic leukemia.

To identify the genetic events that may play an important role in leukemogenesis of childhood ALL, we report for the first time the allelotyping of childhood ALL. Twenty-four cases of childhood ALL were screened for loss of heterozygosity (LOH) using 101 highly polymorphic microsatellite markers, which are distributed among all autosomal chromosomes. For LOH analysis on both chromosomes 9 and 12, 54 childhood ALL samples were examined. The most frequent allelic loss was found on chromosomal arm 9p, where 20 of 50 (40%) informative samples showed LOH. Moreover, nearly 30% of samples that did not have either homozygous deletions or point mutations of the putative tumor suppressor genes CDKN2/INK4A/p16 and INK4B/p15 on chromosomal arm 9p had LOH at D9S171. Loss of chromosomal arm 12p was also frequent (26%). Mutational analysis suggested that the altered gene on 12p is not the cyclin-dependent kinase inhibitor p27/Kip1, which is also on 12p. Several other regions that had LOH included 1p, 4q, 5p, 6q, 7p, 8p, 9q, 10q, 13q, 17p, 17q, 18q, 19q, and 22q. Of 24 patients, 19 (79%) showed allelic loss on at least one chromosomal arm. Samples of two patients (8%) showed LOH on almost all chromosomes. Fractional allelic loss, calculated for each sample as the total number of chromosomal arms lost/total number of arms with information, showed a median value of 0.04 and a mean of 0.123 (range, 0 to 0.95). This fractional allelic loss is lower than those reported for many solid tumors. This analysis shows the extreme power of LOH analysis using microsatellite markers in childhood ALL.

Adolescent↗

Cellular levels of thioredoxin associated with drug sensitivity to cisplatin, mitomycin C, doxorubicin, and etoposide.

Thioredoxin, a cellular thiol, functions as a self-defense mechanism in response to environmental stimuli, including oxidative stress. We first determined cellular levels of thioredoxin in several human bladder and prostatic cancer cell lines resistant to cis-diamminedichloroplatinum(II) (cisplatin). All cisplatin-resistant cell lines had much higher levels of thioredoxin than those in their drug-sensitive parental counterpart. We then, by introducing thioredoxin antisense expression plasmids into human bladder cancer T24 cells, established two bladder cancer cell lines that had decreased levels of thioredoxin. These thioredoxin antisense transfectants showed increased sensitivity to cisplatin and also to other superoxide-generating agents, i.e., doxorubicin, mitomycin C, etoposide, and hydrogen peroxide, as well as to UV irradiation, but not to the tubulin-targeting agents, vincristine, and colchicine. Cellular levels of thioredoxin thus appear to limit sensitivity to various superoxide-generating anticancer drugs in cancer cells.

Antineoplastic Agents↗

DNA topoisomerase II alpha gene expression under transcriptional control in etoposide/teniposide-resistant human cancer cells.

We previously isolated etoposide/teniposide-resistant cell lines from human cancer KB cells, designated KB/VP-2 and KB/VM-4, respectively, and we found that decreased expression of topoisomerase II alpha was associated with the acquisition of etoposide/teniposide resistance in both resistant cell lines. In this study, we studied how the expression of the DNA topoisomerase II alpha gene is regulated in drug-resistant cell lines at the transcriptional level. We first examined whether the decreased topoisomerase II alpha mRNA level was due to a shorter lifetime of mRNA molecules in drug-resistant cell lines. A comparison of the degradation kinetics of topoisomerase II alpha mRNA demonstrated that there was no difference in mRNA stability between both resistant cell lines and their parental counterpart. A run-on experiment with isolated nuclei showed that the transcriptional activity of topoisomerase II alpha gene of both resistant cell lines constituted less than 20% of the parental KB cells. The activity of DNA topoisomerase II alpha promoter in resistant cells was also less than 20% of that in KB cells when transient transfection assays were performed with the promoter-driven bacterial chloramphenicol acetyltransferase gene. Among the several transcription factors that might be involved in DNA topoisomerase II alpha gene expression, expression of Sp3, an inhibitory member of the Sp1 family, was elevated to about 3-fold higher in both resistant cell lines than their parental counterpart. These results indicated that the expression of DNA topoisomerase II alpha gene decreased at the transcriptional level through the enhanced expression of Sp3 in our two etoposide/teniposide-resistant cell lines.

Antigens, Neoplasm↗

Markedly decreased expression of glutathione S-transferase pi gene in human cancer cell lines resistant to buthionine sulfoximine, an inhibitor of cellular glutathione synthesis.

Buthionine sulfoximine (BSO) is a synthetic amino acid that irreversibly inhibits an enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), which is a critical step in glutathione biosynthesis. We isolated three BSO-resistant sublines, KB/BSO1, KB/BSO2, and KB/BSO3, from human epidermoid cancer KB cells. These cell lines showed 10-to 13-fold higher resistance to BSO, respectively, and had collateral sensitivity to cisplatin, ethacrynic acid, and alkylating agents such as melphalan and nitrosourea. Cellular levels of glutathione S-transferase pi (GST-pi) and its mRNA in BSO-resistant cell lines were less than 10% of the parental cells. Nuclear run-on assay showed that the transcriptional activity of GST-pi was decreased in BSO-resistant cells, and transient transfection of GST-pi promoter-chloramphenicol acetyltransferase constructs revealed that the sequences between -130 and -80 base pairs of the 5'-flanking region wer at least partially responsible for the decreased expression of the GST-pi gene. By contrast, gamma-GCS mRNA levels were 3-to 5-fold higher in resistant cell lines than in KB cells, and the gamma-GCS gene was found to be amplified in the BSO-resistant cells lines. GST-pi mRNA levels appeared to be inversely correlated with gamma-GCS mRNA levels in BSO-resistant cells. We further established the transfectants, KB/BSO3-pi1 and KB/ BSO2-pi2, that overexpressed GST-pi, from KB/BSO3, after introducing a GST-pi expression plasmid. These two transfectants had similar levels in gamma-GCS mRNA, drug sensitivity to alkylating agents, and glutathione content at those of KB cells. These findings suggest that the cellular levels of GST-pi and gamma-GCS might be co-regulated in these novel BSO-resistant cells.

Blotting, Southern↗

Maintenance of normal imprinting of H19 and IGF2 genes in neuroblastoma.

H19 and insulin-like growth factor II (IGF2) are among a few genes which have been confirmed to be imprinted in normal human embryonal tissues. This results in monoallelic expression of maternal H19 and paternal IGF2. Loss of imprinting of these genes producing biallelic expression has been observed in Wilm's tumor and embryonal rhabdomyosarcoma, suggesting that an epigenetic change of DNA, in addition to a genetic change in oncogene(s) and/or tumor suppressor gene(s), may be involved in the development of these childhood cancers. Neuroblastoma, which is an embryonal tumor originating from neural crest-derived cells, occasionally occurs in individuals with the Beckwith-Wiedemann syndrome; Wilm's tumor and embryonal rhabdomyosarcoma occur even more frequently in the Beckwith-Wiedemann syndrome; and paternal uniparental disomy of H19 and IGF2 loci (chromosome 11p15) is present in the Beckwith-Wiedemann syndrome. Furthermore, neuroblastoma cell lines express IGF2, and autocrine/paracrine effects of IGF2 have been demonstrated in these cells. Thus, we examined for imprinting of both H19 and IGF2 in primary untreated neuroblastomas using the RsaI and ApaI polymorphisms within these genes, respectively. Seven of 15 tumors were informative for H19 and for IGF2, and all of these cases showed monoallelic expression of both of these genes. These results indicate that loss of imprinting of H19 and IGF2 does not occur in neuroblastomas.

Base Sequence↗