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Biomedical subjects

M Ueki

Publications and source records attributed to M Ueki.

At least 217 records · Page 12Linked to original sources

[An immunohistochemical study with monoclonal antibodies on lymphocytes infiltrating in cervical cancer].

We investigated lymphocytes infiltrating cervical cancer by an immunohistochemical method. Frozen sections (20 with frank invasive cancer, 4 with MIC, 5 with CIS, 6 with dysplasia, 3 normal) were stained by the ABC (avidin-biotin-peroxidase complex) method using monoclonal antibodies to identify functional subsets of lymphocytes. The monoclonal antibodies used were anti Leu 1 (T cell), anti Leu 2a (cytotoxic/suppressor T cell), anti Leu 3a (helper/inducer T cell), anti Leu 10 (B cell) and anti Leu 7 (NK cell). The results were as follows: Many lymphocytes infiltrated and surrounded the cancer nests, and there, T cells predominated over B cells. The intensity of infiltration of T cells was not correlated with the grade and prognosis of cervical cancer. The ratio of Leu 2a+ cells to Leu 3a+ cells tended to change with the advance of cancer. Leu 2a+ cells were relatively predominant in early cases and cases with a good prognosis. There were very few B cells close to cancer nests, and they were not correlated with the grade and prognosis of cervical cancer. NK cells were identified in many cases, but they were scattered and were not correlated with grade and prognosis of cervical cancer.

Antibodies, Monoclonal↗

[Hypergonadotropic ovarian failure in three patients with pituitary hyperplasia].

Three patients with ovulatory disturbances associated with increased production of gonadotropins and normal excretion of estrogen were endocrinologically examined. Patient A was 25 years old and had irregular menstruation of 13 years' duration. Patients B and C were 32 and 36 years old, the former with secondary amenorrhea of 19 years' duration and the latter with one of 2 months. Endocrinological analyses revealed a markedly increased plasma concentration of both LH (greater than 117 mIU/ml) and FSH (greater than 113 mIU/ml) in all three patients. The plasma concentration of estradiol was over 56 pg/ml in A and C before medication, and in the other patient (case B) the plasma estradiol level rose to 53 pg/ml after the administration of clomiphene. There was excessive LH and FSH response in the LH-RH stimulation test. Episodic gonadotropin secretions were observed and two weeks' administration of estrogen plasma concentrations of LH and FSH were suppressed. Computerized tomography revealed a high density area about 9-11 mm in diameter in the sella turcica of all three patients. Patient A underwent surgery via the transsphenoidal approach. Histology shows pituitary hyperplasia. After operation, the elevated LH and FSH concentration decreased to below 30 mIU/ml and the plasma concentration of estradiol and progesterone was increased to 260 pg/ml and 2 ng/ml, respectively.

Adult↗

[An ultrastructural study of the rabbit intraovarian lymphatic capillaries after ovulatory stimulus].

Fine distribution and ultrastructural changes in intraovarian lymphatics were studied at accurately timed intervals after the injection of human chorionic gonadotropin (hCG). Four and six hours after hCG injection, edema around the lymphatic capillaries in the theca externa followed that around the blood capillaries. The lymphatic capillaries were markedly dilated and displayed wide openings between neighboring endothelial cells in them. At these stages, lysosome disappeared from the lymphatic endothelium, while macrophages with numerous lysosomes appeared around the lymphatic capillaries and some of them entered the lumen. Eight hours after hCG injection, the ultrastructure of the lymphatic capillaries resumed the appearance of their pre-injection stage. Three days after hCG injection, lymphatic capillaries were observed among the theca lutein cells, but not among the granulosa lutein cells. Edema around the lymphatic capillaries and openings between neighboring endothelial cells reappeared as shown 4 and 6 hours after hCG injection. Five and seven days after hCG injection, macrophages and degenerated lutein cells were observed in the lymphatic capillaries. Fourteen days after hCG injection, lymphatic endothelium began to degenerate, but that of the blood capillaries showed no degenerative signs. These results suggest that the functions of the lymphatic capillaries are absorption and transport of excess fluid, waste products and hormones.

Animals↗

A comparison of preoperative exfoliative cervical cytology with subsequent histology.

A comparison of the preoperative cervical cytology with the subsequent histology in 441 cases showed a wide variation in the prediction of the histological diagnoses by cytology. There was a precise correlation in 66% of cases. The false negative rate was 11.5% and the false positive rate was 11.2%. These data illustrate the difficulty managing premalignant and malignant disease of the uterine cervix using cytology alone for guidance.

Biopsy↗

[Establishment and characterization of TA-4 producing cell line (OMC-1) originating from a human squamous cell carcinoma of the uterine cervix].

A new human cell line designated OMC-1 was established from a metastatic lesion of Virchow lymph node of a large cell non-keratinizing squamous cell carcinoma of the uterine cervix. OMC-1 was successively subcultured 30 times in about 15 months. The monolayer cultured cells appeared to be epithelial with a pavement-like arrangement and tendency to pile up without contact inhibition. Electronmicroscopy showed desmosomes and well-developed tonofilaments. The population doubling time was 43-70 hours, the saturation density was 1.3-1.7 X 10(5) cells/cm2, the plating efficiency was 23-25% and the mitotic index was 3.3-4.8%. Chromosome studies showed aneuploidy and a modal number of 45. After subcutaneous transplantation into nude mice, the cells grew into solid large cell non-keratinizing squamous cell carcinomas. By the flow cytometric analysis, the phase fractions of the cells was G1 + G0 = 40.1%, S = 24.9% and G2 + M = 35.0%. The OMC-1 cells produced TA-4 in culture media. TA-4 was also demonstrated immunohistochemically in the original tumor tissue, cultured cells and tumors in nude mice.

Animals↗

[Sensitivity to etoposide in cultured cells from cervical squamous cell carcinoma].

The anti-cancer effect of Etoposide was tested in in vitro in cultures of cells taken from a squamous cell carcinoma of the uterine cervix (SKG-IIIb). Growth inhibition was tested by the regrowth assay method, inhibition of DNA synthesis by the uptake of 3H-thymidine, and morphological changes by the method of Limburg et al. The concentrations of Etoposide used were similar to the blood levels recommended for clinical use. The regrowth assay showed that the effective concentration of Etoposide for 50% cell kill was 7.5 micrograms/ml in 2-hour and 1.0 microgram/ml in 24-hour cultures. The 3H-thymidine uptake test showed that a concentration of 13 micrograms/ml for 2 hours or of 3.5 micrograms/ml for 24 hours resulted in 50% inhibition of DNA synthesis. Morphological changes were much greater in the 2-hour cultures at the higher concentration of Etoposide than in the 24-hour cultures at the lower concentration. Investigation of the drug sensitivity by cell kinetics disclosed prolongation of the cell cycle occurring after 96 hours at 1.0 microgram/ml and inhibition of cell cycle progression occurring after 24 hours at 10.0 micrograms/ml and after 4 or 8 hours at 50.0 mu/ml. Thus, the anti-cancer effect of Etoposide on SKG-IIIb depends on both the concentration and exposure time and is related to its ability to inhibit cell growth and DNA synthesis and to cause morphological changes in the cancer cells.

Carcinoma, Squamous Cell↗

[Follow-up studies after incomplete excision of cervical carcinoma in situ].

To understand the biological nature and the treatment of cervical carcinoma in situ (CIS), numerous (216) incompletely excised specimens obtained by conization at Auckland University's National Women's Hospital were examined and the histological findings with long-term follow-up were correlated. Follow-up studies were possible in 211 patients for two years or more; 88.4% were followed up for at least five years. There was no evidence of recurrence in 62.9% of the total series. Recurrences were related to the area of CIS in the cervix, and the incompletely excised sites and blocks. Micro-invasive carcinoma was found in four patients (1.90%) and invasive carcinoma (stage Ib "occ") in two (0.95%). The following conclusion has been drawn: If CIS is incompletely excised by conization, follow-up examinations are essential. When the CIS is small in the cervix or it is incompletely excised only outside the endocervix, spontaneous disappearance can be expected. In the entire series, including patients in whom the incomplete excision left a fairly large CIS remnant, the nonrecurrence rate was unexpectedly high. These findings suggest that the continued existence of incompletely excised CIS is significantly inhibited by a considerable damage to the conization.

Carcinoma in Situ↗

Amino acid sequence of histone H1 at the ADP-ribose-accepting site and ADP-ribose X histone-H1 adduct as an inhibitor of cyclic-AMP-dependent phosphorylation.

The ADP-ribosylation site of histone H1 from calf thymus by purified hen liver nuclear ADP-ribosyltransferase was determined and effects of the ADP-ribose X histone-H1 adduct on cAMP-dependent phosphorylation of the histone H1 were investigated. ADP-ribosylated histone H1 was prepared by incubation of histone H1, 1 mM [adenylate-32P]NAD and the purified ADP-ribosyltransferase. N-Bromosuccinimide-directed bisection of ADP-ribosylated histone H1 showed that the NH2-terminal fragment (Mr = 6000) was modified and contained serine residue 38, the site of phosphorylation by cAMP-dependent protein kinase. Digestion of the NH2-terminal fragment with cathepsin D and trypsin, and purification of this fragment, using high-performance liquid chromatography, yielded a radiolabelled single peptide corresponding to residues 29-34 of histone H1, containing the arginine residue as the ADP-ribosylation site. These results indicate that ADP-ribosylation of histone H1 occurs at the arginine residue 34, sequenced at the NH2-terminal side of the phosphate-accepting serine residue 38. Phosphorylation of histone H1 from calf thymus by cAMP-dependent protein kinase was markedly reduced when histone H1 was ADP-ribosylated. Kinetic studies of phosphorylation revealed that ADP-ribosylated histone H1 was a linear competitive inhibitor of histone H1 and a linear non-competitive inhibitor of ATP.

Adenosine Diphosphate Ribose↗

Characteristic of antinociceptive effect of a tetrapeptide, Asn-Ala-Gly-Ala (NAGA).

The characteristic of the antinociceptive effect of a tetrapeptide, Asn-Ala-Gly-Ala (NAGA), was examined. Intracisternal (i.cist.) administration of NAGA to mice produced dose-dependent and long-lasting antinociceptive effect as evaluated by the hot plate and tail flick methods. NAGA-induced antinociception was reversed by naloxone (2 mg/kg), reserpine (2 mg/kg X 2 d) and alpha-methyl-p-tyrosine (100 mg/kg). NAGA (10 microM) did not significantly affect the actions of opioid peptides on the electrically evoked twitches of the myenteric plexus-longitudinal muscle strips from the guinea-pig esophagus and strips of the mouse vas deferens. NAGA-induced antinociception was scarcely affected by p-chlorophenylalanine (PCPA, 300 mg/kg X 2 d) and methysergide (2 mg/kg). From the above results, it was suggested that the antinociceptive effect of NAGA may involve the participation of endogenous opioid peptides and endogenous catecholamines.

Analgesics↗

[A study of bone metastasis of cervical carcinoma by bone scintigraphy].

In carrying out bone scintigraphy in 224 cases over the 5 years from June, 1978 to May, 1983 as a part of the post-treatment management of cervical carcinoma, we obtained the following findings concerning bone metastasis. Bone metastases were seen in 12.5% (28 cases) of the subjects, about 6% of the total post-treatment cases of cervical carcinoma in the corresponding period (466 cases). Bone metastases were seen in 9.3% (16/172) of post-operative cases, compared with 23.1% (12/52) of non-operative cases. Bone metastases were not seen in clinical stages Ia through IIa (49 cases) but were seen in IIb or higher stages. Bone metastasis rates by histological type, according to WHO classification, were 12.8% (26/203) in squamous cell carcinoma, 5.9% (1/17) in adenocarcinoma, and 25% (1/4) in adenosquamous carcinoma. Among the squamous cell carcinoma cases, small cell non-keratinizing type had the highest bone metastasis rate (p less than 0.05). Of 172 post-operative cases, 20.8% (11/53) of those with lymph node metastasis exhibited bone metastasis, higher than the 4.2% (5/119) in cases without lymph node metastasis. As to CPL classification, bone metastasis was seen more often in L type (18.8%) than C(0.0%) or P types (6.6%). Our risk classification of 168 cases demonstrated that bone metastasis was not seen in risk I group (74 cases), but was seen in 6.7% (1/17) of risk II group and in 19.0% (15/79) of risk III group. Twenty-eight cases with bone metastasis included 11 cases with local recurrence, 8 with pulmonary metastases, 4 with hepatic metastases and 4 with Virchow's lymph node metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Possible participation of Ca2+, Mg2+-dependent endonuclease in liver DNA fragmentation after N-methyl-N-nitrosourea treatment.

We examined the fragmentation of DNA treated with N-methyl-N-nitrosourea under conditions in which Ca2+, Mg2+-dependent endonuclease is active. The molecular mass of DNA found in mouse liver slices treated with methylnitrosurea in the presence of Ca2+ plus Mg2+ was 4 X 10(5) Da. Similar results were obtained with a reconstituted system containing partially purified Ca2+, Mg2+-dependent endonuclease and methylnitrosurea-treated DNA. The enzyme extensively cleaved methylnitrosurea-treated DNA, compared with non-treated DNA. The methylnitrosurea-treated nuclear proteins obtained from mouse liver nuclei had no effect on the DNA fragmentation by the enzyme. Using closed-circular DNA treated with methylnitrosurea, the enzyme produced single-strand cuts in the DNA, as was seen in non-treated, closed-circular DNA, however, the rate of hydrolysis was increased. Ca2+, Mg2+-dependent endonuclease thus warrants further investigation, with regard to the precise mechanism of extensive degradation of DNA in cells treated with carcinogenic alkylating agents.

Animals↗

Two new opioid delta-receptor ligands: a highly selective agonist and a potent selective antagonist in in vitro isolated preparations.

N,N-Diallyl derivatives of enkephalin analogues were chemically synthesized, and their biological activities were estimated in vitro isolated preparations. N,N-Diallyl-[D-Ala2, D-Leu5]-enkephalin [test compound I] at doses up to 10 microM did not inhibit the electrically-evoked contractions of guinea-pig ileum, which had been suggested to contain opioid mu- and kappa-receptors, but it significantly depressed the contractions of mouse vas deferens, which had been indicated to contain mu-, kappa- and delta-receptors, suggesting that test compound I did not act on both mu- and kappa-receptors, but acted on delta-receptors. Additionally, the Ke (equilibrium dissociation constant) values against test compound I of naloxone were approximately 30 nM and similar to those of Mr 2266, also indicating that test compound I acted as a delta agonist. Moreover, the Ke values of ICI 154129 against compound I were approximately 340 nM, strongly suggesting that test compound I acted as a delta agonist. The Ke values of bis-[N,N-diallyl-[D-Ala2, Leu5]-enkephalyl]-cystine [test compound II] against [D-Ala2, D-Leu5]-enkephalin in mouse vas deferens and morphine or ethylketocyclazocine in guinea-pig ileum were 44.9 nM and 5.00 or 11.3 microM, respectively, showing that test compound II was a potent selective opioid delta antagonist. In conclusion, among compounds synthesized, two new opioid delta-receptor ligands, one being a highly selective agonist and the other being a potent selective antagonist in in vitro isolated preparations, were found in the present study.

Animals↗

[Peplomycin sensitivity of various types of human gynecological cultured tumor cells].

Various types of human gynecological cultured tumor cells were tested for the sensitivity to Peplomycin (PEP), an effective antitumor antibiotic for squamous cell carcinomas, by the regrowth assay method together with morphological observation. Bleomycin-hydrolase activity of these cell lines was also compared in cell-free extracts by assaying the conversion of Bleomycin into its deamidated from (HPLC method). SKG-I, SKG-II, SKG-IIIb cells derived from squamous cell carcinoma of the cervix and RKN cells derived from myosarcoma of the ovary were much more sensitive to PEP than other cell lines. PEP was found to be mainly a time-dependent drug, but also concentration dependent. The effect of PEP on cell morphology was characterized by the appearance of enlarged cells and swelling nuclei. The specific activities of Bleomycin-hydrolase in SKG-I, SKG-II, SKG-IIIb cells were shown to be relatively lower than that in other cell lines. These results suggested that cervical squamous carcinoma cells and ovarian myosarcoma cells were sensitive to PEP and Bleomycin-hydrolase activity was one of factors which decided the PEP sensitivity of human cultured tumor cells.

Antibiotics, Antineoplastic↗