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Biomedical subjects

N Wake

Publications and source records attributed to N Wake.

At least 19 recordsLinked to original sources
PubMed1992

Chromosomal deletions and K-ras gene mutations in human endometrial carcinomas.

Forty-two endometrial carcinomas of various stages of progression were analyzed to search for loss of chromosomal regions and for point mutations of ras genes and amplification of Int-2 gene. This approach is particularly favorable for observation of genetic events and their significance in the process of neoplastic conversion by considering the clinico-pathological characteristics of each tumor. At least 3 genetic events, including 18q, 17p deletions, and point mutations at codon 12 of the K-ras gene, are implicated in the development of endometrial carcinomas. Likely targets for allelic losses on chromosomes 18q and 17p are the DCC gene and the p53 gene sequences, respectively. Overall numbers of allelic losses in individual tumors appeared to increase in case of advanced stage tumors, thereby indicating the association of allelic loss accumulation with tumor progression. The genetic features seen in 2 juvenile-type adenocarcinomas and 2 clear-cell carcinomas suggested the possibility that etiological factors providing selective pressure for particular mutation sub-sets during carcinogenesis are probably heterogeneous.

Adult↗
PubMed1992

Chromosome alterations contribute to neoplastic progression of transformed rat embryonal fibroblasts.

Three types of transformants derived from rat embryonal fibroblasts (REFs) corresponding to the different progressional stages were obtained: TF1 (human papillomavirus type 16 E7 (HPV16 E7) transfection alone) and TF2 (E7 plus adenovirus type 12(Ad12) E1b were immortalized, TF3 (E7 plus adenovirus type 5 (Ad5) E1B) was anchorage-independent but not tumorigenic, and TF4 (E7 plus EJ-ras) was tumorigenic. Cytogenetic investigations revealed that the cells carrying specific chromosomal abnormalities expanded clonally in three of the five TF4 tumorigenic clones, in contrast to the TF1-TF3 non-tumorigenic clones, which showed a normal karyotype. By the inoculation of TF4 into syngeneic rats, 8 tumor-derived clones were obtained. Clonal expansion of cells carrying specific chromosome changes was also remarkable in these tumor-derived clones. However, the type of rearrangements and the chromosomes involved in the abnormalities were not identical. In addition, it was shown that chromosome constitutions of the parental TF4 transformants were apparently inconsistent with those of their tumor-derived clones. However, the clonal nature of abnormalities observed in the parental and the tumor-derived clones suggested that these genetic events of cellular genomes corresponded with and possibly contributed to the progression of malignant phenotypes of cells.

Adenoviridae↗
PubMed1992

The characteristics of erythrocyte Na+ transport systems in normal pregnancy and pregnancy-induced hypertension.

OBJECTIVE: To assess the role Na plays in the pathogenesis of pregnancy-induced hypertension (PIH). METHODS: We assessed Na and K content, the maximum number of ouabain binding sites, Na(+)-Li+ countertransport and Na(+)-K+ cotransport in erythrocytes from women with untreated PIH, normal pregnant women and healthy non-pregnant women. RESULTS: In normal pregnancy, the Na content of erythrocytes decreased, accompanied by the activation of Na excretion systems. In women with PIH, the Na content of erythrocytes and the Na(+)-K+ cotransport activity significantly increased, whilst erythrocyte K content and the maximum number of ouabain binding sites significantly decreased, compared with observations in normal pregnancy. In both normal pregnancy and PIH, there were no differences in Na(+)-Li+ countertransport. CONCLUSIONS: These results suggest that the increase of erythrocyte Na content in women with PIH may be contributed to by a reduction in the number of ouabain binding sites, whilst Na(+)-K+ cotransport and Na(+)-Li+ countertransport may compensate for this effect in women with PIH.

Adult↗
PubMed1992

Thyroxine-binding globulin variant (TBG-Kumamoto): identification of a point mutation and genotype analysis of its family.

Thyroxine-binding globulin (TBG) is the major thyroid hormone transport protein. Several inherited TBG variants resulting in partial or complete TBG deficiencies have been shown to be caused by either one or two nucleotide substitutions, or one nucleotide deletion in the coding regions of the TBG gene. In this report, a Japanese female patient (proband) with hyperthyroid state, whose lower TBG levels did not return to normal under the euthyroid state after treatment was examined. Genomic DNA samples from the proband with thyroxine-binding globulin deficiency (termed TBG-Kumamoto) and her family were subjected to the polymerase chain reaction, and the generated DNA fragments were sequenced. A single nucleotide substitution in the codon for the amino acid 363 of native TBG molecule (CCT to CTT) was found, resulting in the replacement of proline by leucine. It was revealed that the proband was a heterozygote and her father was a hemizygote. The mutation was confirmed by the allele-specific amplification of genomic DNAs from the proband and her father using oligonucleotide primers of normal or mutant residues at the 3' position in the polymerase chain reaction. These results indicate that the abnormality of TBG-Kumamoto is the consequence of this mutation. Genetically, this point mutation observed in TBG-Kumamoto might be classified as a new type of TBG deficiency.

Adult↗
PubMed1991

[Identification of a chromosome carrying a putative tumor suppressor gene in human choriocarcinoma by microcell-mediated chromosome transfer].

There are two main mechanisms of origin for complete hydatidiform mole; a) fertilization of an empty egg by a haploid sperm followed by duplication, and b) fertilization of such an egg by two haploid spermatozoa. It is widely accepted that, of all forms of pregnancy that had to choriocarcinoma, the risk associated with moles is by far the highest. Homozygous expression of a recessive mutation of moles has been assumed to associate with this propensity to malignancies. Alterations of several tumor suppressor genes together with activation of oncogenes are assumed to be necessary for choriocarcinogenesis. Genetic characteristics shown in the moles suggest that the former alterations are especially important to explore the multistep conversions to malignancies. Thus, individual chromosomes derived from normal cells were introduced into choriocarcinoma cells via microcell fusion. Evaluation of tumorigenicity in microcell hybrids suggested that chromosome #7 carried a putative tumor suppressor gene for choriocarcinoma. The gene imprinting or recessive mutation may be responsible for the inactivation of such a gene, being able to correspond with the high propensity to malignancy of moles.

Animals↗
PubMed1990

Isolation of clones resistant to 6-thioguanine and G418 from HHUA endometrial carcinoma cells and their application to cell hybridization.

Two kinds of clones were isolated successfully from the HHUA 95 cells that were derived from a human well-differentiated adenocarcinoma of endometrium, with 6-thioguanine (6-TG) selection and transfection with plasmid containing the neo gene (pSV2 neo). One clone was resistant to the 6-TG (6-TGr 95) and the other to both the 6-TG and the G418 (6-TGr-neor 95). Karyotypes of these three kinds of cells were normal, even though random chromosome abnormalities were observed in some cells. Two types of cell fusion were performed: one consisted of the hybridization between 6-TGr 95 cells and normal human fibroblasts (HF), and the other, between 6-TGr-neor 95 and human choriocarcinoma cells (CC1). Tumorigenicity of both hybrid cell types was completely suppressed. Complementation for genetic lesions given by cell hybridization was assumed to be responsible for the suppression of tumorigenicity. These results suggest that genetic losses played an essential role in the evolution of the malignant phenotype of endometrial carcinoma cells. The data obtained from the endometrial carcinoma could not be used directly for the understanding of suppression mechanisms of choriocarcinoma.

Cell Fusion↗
PubMed1990

Bilaterally persistent sciatic arteries.

A very rare developmental anomaly showing bilaterally persistent sciatic arteries was found in a cadaver of 89 year old female. Both right and left sciatic arteries arose from the internal iliac arteries and appeared between the piriformis and superior gemellus muscles at the buttock, being about 10 mm in diameter. Each artery, which accompanied by the companion vein, i.e. sciatic vein, sent the branches to the gluteus maximus and the flexor muscles of thigh. On the other hand, the femoral arteries of both lower limbs were smaller than usual, measuring 4.7 mm in left and 5.2 mm in right. The terminal vessels of those were joined to the sciatic arteries at the popliteal fossa. In addition, the present case also had another developmental anomaly, i.e. superficial brachial artery in the right upper limb.

Aged↗
PubMed1990

[Cytogenetical study on the etiology of partial mole].

The cytogenetical etiology of partial mole (PM) was studied by means of the Q-banding technique in 49 cases during the period between Sep. 1976 and Nov. 1986. Moreover, histological examinations were performed in 39 cases concentrating on the existence of fetal components and trophoblastic hyperplasia, etc. The results were as follows. 1. Karyotype analysis showed triploidy (24 cases), normal diploidy (10 cases), trisomy (9 cases) and other anomalies (mosaic, translocation etc.) (6 cases). These results are quite different from those of many western authors, who reported that most cases of PM are triploidy. 2. The criteria of PM in Japan differ from those of WHO Scientific Group in regard to trophoblastic hyperplasia. 3. Our cases were reclassified on the basis of the definition drawn up by the WHO Scientific Group. Nevertheless, the rate of triploidy was only 54.5%, which is lower than that reported by many western authors. These results show that the development of PM cannot be explained cytogenetically at present, in contrast with complete mole.

Diploidy↗
PubMed1990

Multiple chromosomes carrying tumor suppressor activity for a uterine endometrial carcinoma cell line identified by microcell-mediated chromosome transfer.

Putative tumor suppressor genes can be mapped to specific chromosomes by the introduction of individual chromosomes derived from normal cells via microcell fusion. We have examined whether a highly malignant human uterine endometrial carcinoma cell line, HHUA, can be suppressed by only one normal chromosome or by multiple chromosomes. A library of mouse A9 clones containing different human chromosomes tagged with the pSV2-neo plasmid DNA were constructed. Transfer by microcell fusion of either chromosome 1, 6, 9, 11, or 19 into the HHUA tumor cell line was performed, and the abilities of the microcell hybrids to form tumors in nude mice were examined. The introduction of a chromosome 19 had no effect on the tumorigenicity of the cells, whereas microcell-hybrid clones with an introduced chromosome 1, 6 or 9 were completely suppressed for tumorigenicity. A decrease in tumor-take incidence in some but not all clones was observed following the introduction of a chromosome 11. The nontumorigenic microcell hybrids with an introduced chromosome 1 differed from the nontumorigenic microcell hybrids with an introduced chromosome 6, 9, or 11. A large percentage of hybrids with chromosome 1 senesced and/or showed alterations in cellular morphology and transformed growth properties in vitro. No growth or morphology alterations were observed following transfer of the other chromosomes. These results may indicate that more than one chromosome carries a tumor suppressor gene(s) for this human uterine endometrial carcinoma cell line and support the hypothesis that multiple tumor suppressor genes control the tumorigenic phenotype in the multistep process of neoplastic development.

Cell Fusion↗
PubMed1989

Methotrexate-resistant mechanisms in human choriocarcinoma cells.

Choriocarcinoma cells grown in the presence of methotrexate (MTX) developed resistance in two ways. HCCM-derived sublines (relatively high MTX resistance) produced enhanced levels of dihydrofolate reductase (DHFR) and had impaired transport of MTX. Altered transport was the primary determinant of response in CC1-derived sublines (low MTX resistance). Since the selection procedures used were identical, it was assumed that altered MTX transport was insufficient to account entirely for the various degrees of resistance. An increased level of DHFR activity was necessary for the development of high MTX resistance. The overproduction of DHFR was the consequence of amplification of the DHFR gene sequence. The incidence of double minutes (DMs) in metaphase paralleled the degree of resistance. However, DMs were also present in cells not showing DHFR gene amplification. Mechanisms other than DHFR gene multiplication were responsible for the de novo synthesis of DMs.

Blotting, Southern↗
PubMed1989

[Omentum in the management of thoracic surgery: especially its application to tracheobronchial surgery].

Omentum is now not only policeman of the abdomen but also of the thorax. We applied omental pedicle flap in the management of 14 patients with thoracic surgery including chest wall reconstruction, empyema, thoracic skeletal infection and tracheobronchial problems. Especially, tracheobronchial reconstruction using omental pedicle flap for the patient combined with lung cancer (T4N2M0 STAGE IIIB) and asthma under steroid therapy was reported. The case was 71-year-old man with complaint of hemosputum. He had 5-6 year history of bronchial asthma with disturbed pulmonary function of % VC 44%, FVC1.0% 37%. Bronchoscopic study revealed the tumor invading the right side of trachea originating from right upper bronchus with histological diagnosis of moderately differentiated squamous cell carcinoma. Preoperatively, he experienced a heavy asthma attack which was controlled by steroid administration. Following extended right sleeve upper lobectomy, we applied omental pedicle flap around the reconstructed portion for the protection of infection, impaired wound healing due to postoperative steroid therapy and strong tension at anastomoses. Postoperative course was satisfactory. We suggest omental pedicle flap is an effective surgical armamentarium in the management of tracheobronchial surgery for the patient with strong anastomotic tension, immunocompromised condition, preoperative irradiation at bronchial stump and use of drug causing delayed wound healing (steroid, anticancerous drug etc).

Aged↗
PubMed1989

[Somatic cell hybrids used in cytogenetic analysis of transformation mechanism of uterine endometrial cell].

6-Thioguanine and Neomycin resistant human endometrial carcinoma cells were established from parental HHUA 95 cells in the present study. The karyotype was 46,XX although chromosome abnormalities had been observed occasionally. Cell hybrids between 6-TGr neor 95 and rat immortalized, non-tumorigenic 3Y1 cells were formed to analyze for cosegregation of chromosomes and tumorigenicity. However, the morphology of 3 hybrid clones was a spindle form, similar to the 3Y1 cells. In spite of the consistent presence of human chromosomes, negative anchorage independent growth in these clones suggested that none of the chromosomes involved in fused cells was associated with tumorigenicity of endometrial carcinoma. Loci on a few human chromosomes of a normal cell cause suppression in several hybrid systems. Cell fusion between 6-TGr 95 and normal human fibroblasts (HF) was performed to confirm whether this is also true in endometrial carcinoma. Hybrid cells had four copies of homologous chromosomes (two from each of the parent cells). These had a polygonal appearance, being similar to the HHUA 95 cells. Both anchorage independence and tumorigenesis were negative. Those results suggested that malignant transformation of endometrial cells was the result of multiple genetic changes. In this respect, the loss of genes implicated in the suppression plays an important role in endometrial carcinogenesis.

Adenocarcinoma↗
PubMed1987

Nonsurgical therapy to preserve oviduct function in patients with tubal pregnancies.

Surgical treatment for tubal pregnancies greatly impairs the subsequent fertility of patients because of salpingectomy and its complicated adhesions. Nonsurgical methotrexate therapy was developed to avoid such complications. Although early detection was of prime importance, resolution of ectopic pregnancy was obtained in 22 patients (95.7%) with methotrexate administration alone. Patency of the oviducts was evaluated with hysterosalpingography and/or laparoscopy in 19 patients after termination of methotrexate treatment. In 10 of 19 patients (52.6%), complete patency of the involved oviduct confirmed the validity of this regimen. Severe side effects were not observed in any of the 23 patients.

Adult↗
PubMed1987

Hydatidiform mole: parental chromosome aberrations in partial and complete moles.

The relationship between parental constitutional chromosome abnormalities and the development of hydatidiform mole was evaluated in series from four institutions. Karyotype analysis was performed on blood samples from 237 patients with a pathological diagnosis of complete mole and 217 of their spouses. One patient was found to have a constitutional balanced translocation, t(11;18), while one spouse was found to have a balanced translocation, t(4;20). Among 125 patients with partial mole and 106 of their spouses, one male was found to be a translocation carrier, t(13;14). No significant increase in the frequency of translocations in the parents of complete moles was found in any of the series considered separately or together. Data from the combined series show no evidence of constitutional parental chromosome aberrations as an aetiological factor in the development of molar pregnancies.

Chromosome Aberrations↗