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Biomedical subjects

T Akiyoshi

Publications and source records attributed to T Akiyoshi.

At least 127 records · Page 7Linked to original sources

Epidermal ridge formation in the human fetus: a correlation to the appearance of basal cell heterogeneity and the expression of epidermal growth factor receptor and cytokeratin polypeptides in the epidermis.

This paper aims to clarify an expression of epidermal growth factor receptor (EGFR) and cytokeratin 10 and/or 11 in relation to primary and secondary epidermal ridge formation of the human fetus. Firstly, scanning electron microscopy revealed heterogeneity in basal cell morphology during epidermal ridge formation. Basal cells had a uniform, smooth, and polygonal dermal surface until formation of the primary epidermal ridges. Thereafter, the dermal surface became ruffled and elliptic except at the primary epidermal ridges. Secondly, EGFR was detected by monoclonal antibody and autoradiography using 125I-EGF. The antibody reacted with primary epidermal ridge, stratum basale, stratum intermedium, and outer layer of sweat duct. The reactivity became stronger at the primary epidermal ridge than at the secondary one. The binding of 125I-EGF was concentrated in the primary epidermal ridge and sweat duct. Thirdly, cytokeratin 10 and/or 11, a maturation marker of keratinocytes, was detected by monoclonal antibody. The antibody reacted only with the stratum intermedium before secondary epidermal ridge formation. Afterward, it also reacted with the stratum basale of the secondary epidermal ridge but never reacted with that of primary epidermal ridge. The results indicate that basal cells of the secondary epidermal ridge enter the maturation process and suggest a localization of epidermal stem cells on the primary epidermal ridges. Concerning epidermal ridge formation, we suppose that the formation of the primary epidermal ridge causes the segregation of the epidermal stem cells, and that the increased density of the basal cells between the two primary epidermal ridges brings about the change in their dermal surface shape and the formation of the secondary epidermal ridge.

Cell Differentiation↗

Differential effects of ursodeoxycholic acid and ursocholic acid on the formation of biliary cholesterol crystals in mice.

The preventive effect of 3 alpha, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid (ursocholic acid) and ursodeoxycholic acid on the formation of biliary cholesterol crystals was studied in mice. Cholesterol crystals developed with 80% incidence after feeding for five weeks a lithogenic diet containing 0.5% cholesterol and 0.25% sodium cholate. When 0.25% ursocholic acid or ursodeoxycholic acid was added to the lithogenic diet, the incidence as well as the grade (severity) of the gallstones were reduced. Plasma and liver cholesterol levels were decreased by ursodeoxycholic acid but not by ursocholic acid. Gallbladder cholesterol and phospholipid levels were decreased by both bile acids. The biliary bile acid level was decreased by ursocholic acid but not by ursodeoxycholic acid. After feeding ursocholic acid, its level in the bile was about 25% and the levels of cholic acid and beta-muricholic acid decreased. Fecal sterol excretion was not changed by ursocholic acid, but was increased by ursodeoxycholic acid. After feeding ursocholic acid, fecal excretion of deoxycholic acid, cholic acid, and ursocholic acid increased. No differences were found between mice, with or without gallstones, in plasma and liver cholesterol levels, biliary phospholipid and bile acid levels, fecal sterol and bile acid levels, and biliary and fecal bile acid composition. The results suggest that the lower incidence of crystal formation after treatment with ursocholic acid is probably by a different mechanism than with ursodeoxycholic acid. In the mouse model, ursodeoxycholic acid exerts its effect at least partially, by decreasing cholesterol absorption. Ursocholic acid is well absorbed and excreted into bile and transformed into deoxycholic acid by the intestinal microflora in mice.

Animals↗

Inhibitory effects of prostaglandin F2 alpha on mammary carcinogenesis induced by ethyl methanesulphonate in rats.

The effect of prostaglandin F2 alpha (PGF2 alpha) on mammary carcinogens was examined for a new system in female rats, using ethyl methanesulphonate (EMS). The rats were given EMS orally for a period of 12 weeks starting at age 4 weeks. Mammary carcinomas were first detected at the 16th week and were found in all surviving rats at the 32nd week. The concomitant administration of PGF2 alpha for 8 weeks made the development of tumor retarded; i.e., the carcinomas were first detected at the 30th week and final tumor incidence at the 44th week was 61.1%. The incidence of developing mammary carcinomas and multiplicity (number of mammary carcinomas per rat) were significantly lower in PGF2 alpha treated rats than in those given EMS alone. The inhibitory effect of PGF2 alpha on tumor development was apparent when PGF2 alpha was concomitantly given to the rats with EMS at age 4 weeks, while PGF2 alpha injections after oral administration of EMS at age 16 weeks did not significantly retard tumor development. Histologically, no significant difference in morphology was observed between PGF2 alpha-treated and PGF2 alpha-non-treated rats in either the cancerous or noncancerous mammary tissues. The finding demonstrates that PGF2 alpha inhibits the development of EMS-induced mammary carcinomas when given to younger rats, presumably by affecting the hormonal status rather than by direct action on the mammary glands.

Animals↗

Extraskeletal osteosarcoma in the axilla associated with breast carcinoma.

A case of extraskeletal osteosarcoma arising in the axilla in a 77-year-old woman is described. Because of its association with an ipsilateral breast carcinoma, the axillary mass was at first assumed to be a lymph node with metastatic breast carcinoma. The occurrence of extraskeletal osteosarcoma in the axillary is rare and association with breast carcinoma has never, to our knowledge, been described.

Aged↗

[Gene analysis in human hematopoietic malignancies].

We analyzed the T-cell receptors and immunoglobulin genes in 140 cases of hematopoietic malignancies, including ALL/LBL, malignant lymphomas, AILDs, Hodgkin's disease, ATL and CLL. In many cases, the findings obtained by immunoassociated gene analysis were in parallel to the phenotypic findings. Gene analysis is useful to determine the clonality and the lineage of malignant cells. However, 10-30% cases appeared bigenotype. In some cases, oligoclonalities were recognized. The relationship to the prognosis in these cases was discussed. The development of gamma delta- and alpha beta-cells on T-cell ontogeny was elucidated. Some T-cell leukemic lines were found to be pre-alpha beta T-cells with some consensus characteristics. We also analyzed the V beta family of 15 alpha beta T-cell leukemia cell lines using six V beta cDNA probes. This approach may be useful to determine the clonality of T-cell malignancies. The method of using a PCR system on immunoassociated genes has been described. The PCR method, using the super variable region as a tumor specific fragment, is valuable in the detection of the residual cells of lymphoma and leukemia at a concentration of 1/10(5) cells.

Gene Rearrangement, B-Lymphocyte↗

Inhibitory effects of estrogen on the growth of a human esophageal carcinoma cell line.

In order to accurately determine sex hormone dependency and hormone responsiveness in human esophageal carcinoma, the effects of sex hormones on the growth of esophageal carcinoma cell lines, KSE-1 and KSE-2 cells, were examined in vitro and in vivo. Cell proliferation of cultured KSE-1 cells was inhibited by treatment of estradiol and enhanced by dihydrotestosterone (DHT), whereas KSE-2 cells were unaffected by these sex hormones. The heterotransplanted tumors of KSE-1 cells in nude mice possessed estrogen receptor (ER) and androgen receptor (AR), while the tumors of the KSE-2 cells had neither ER nor AR. When the tumor growth rates and serum hormone levels were monitored during the continuous administration of either estradiol or DHT, no significant differences were observed in either the serum hormone levels or tumor growth rates between male and female mice. The administration of estradiol significantly inhibited the growth of ER-positive and AR-positive KSE-1 tumors in both males and females in conjunction with an increase in the estradiol levels and a decrease in the DHT levels in the serum. However, the growth of ER-negative and AR-negative KSE-2 tumors was not influenced by either estradiol or DHT administration. These results suggest that the in vivo growth of human esophageal carcinoma cells with sex hormone receptor is influenced by circulating hormone levels and can be manipulated by systemic estradiol administration.

Animals↗

Estrogen receptor status and effects of endocrine ablative surgery in ethyl methanesulphonate-induced rat mammary carcinoma.

An experimental model of rat mammary carcinoma induced by oral administration of ethyl methanesulphonate (EMS) was characterized with reference to estrogen receptors (ER) and hormone dependency. After the administration of EMS, the mammary carcinomas developed more rapidly in the 4-week old rats than in the 16-week old rats. The developed mammary carcinomas were related to the ER status. Tumor development was prevented by ablative oophorectomy prior to EMS administration, but only partially, by adrenalectomy. These inhibitory effects on tumor development were more obvious when ablative surgery was performed on younger rats at age 4 weeks. In rats subjected to oophorectomy at after EMS administration at age 16 weeks, tumor induction was retarded but not completely prevented. Thus, it appears that mammary tumors induced by EMS are dependent on ovarian hormones and that mammary glands of the younger female rats are more sensitive to carcinogenic actions of EMS.

Adrenalectomy↗

Preoperative cell-mediated immune function and the prognosis of patients with gastric carcinoma.

The cell-mediated immune function of 83 patients with gastric carcinoma was assessed preoperatively and the results were compared to that of 52 patients with benign lesions. The data were subjected to an analysis in order to evaluate their prognostic significance. The abilities to induce allogeneic cytotoxicity and to produce interleukin 2 (IL2) in patients with stage IV carcinoma were significantly depressed, as compared to those in patients with benign lesions, whereas natural killer (NK) cell activity was not significantly impaired. There was no significant correlation among these immune functions. When the patients were stratified into two groups, those who had high (greater than the mean value in patients with benign lesions) and low (less than the same value) values of these immune reactivities, the survival of patients with high NK activity (greater than or equal to 43%) was significantly better, as compared to that of patients with low cytotoxicity (less than 43%). However, there was no correlation between the survival and allogeneic cytotoxicity in these patients. The high ability to produce IL2 (greater than or equal to 1.3 U/ml) correlated with the better survival in the patients, but not in the group of patients who underwent curative resection.

Cytotoxicity, Immunologic↗

Bile acid composition in brown pigment stones.

The bile acids in brown pigment stones and gallbladder bile were fractionated into free acids, glycine and taurine conjugates, and sulfates using diethylaminohydroxypropyl Sephadex LH-20 (DEAP-LH-20) column chromatography and were quantitated by gas chromatography. Twenty-eight cases of brown pigment stones were studied and divided into two groups: those with and those without bacteria possessing bile acid-deconjugating activity. In the former, free bile acid amounted to 62 +/- 34% of the total bile acid, while in the latter, only 0.1% of total bile acid was free bile acid. The fraction of total bile acid made up of free bile acids was found to be consistently higher in brown pigment stones than in the corresponding bile, irrespective of the presence or absence of biliary infection. Free bile acid is present in negligible amounts in normal bile. Total bile acid concentration in the bile of patients with brown pigment stones was significantly less than that of controls (13 vs 50 mg/ml). Biliary infection is almost always present in cases with brown pigment stones. These findings suggest that bacterial infection is present at the initiation of brown pigment stone formation as well as during the period of ensuing stone growth.

Bacterial Infections↗

The effect of recombinant interleukin 2 in combination with mitomycin C on advanced cancer.

We recently discovered that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C (MMC) administration. Based on our clinical findings, we designed a treatment regimen comprised of MMC 12 mg/m2 given intravenously on day 1 and recombinant interleukin 2 (rIL 2) 700 U/m2 given intravenously every 12 hr from day 4 through day 8, when the generation of LAK cells had been shown to be markedly increased. Ten patients with various advanced carcinomas for which standard therapy had failed or no standard therapy was available, were treated with this regimen. Of these ten, three had a partial response and three others had a minor response. Fevers were common and anemia occurred in four patients, but nevertheless, severe toxicity was not encountered. These results indicated that rIL 2 in combination with MMC might be effective against advanced carcinoma without causing severe toxicity when these drugs are used in an appropriate combination.

Aged↗

Clinical and microangiographic studies on rupture of the E.P.L. tendon after distal radial fractures.

The authors have treated 14 cases of spontaneous rupture of extensor pollicis longus tendon after fractures of the distal end of the radius, most of which were undisplaced or only slightly displaced. A microvascular study on five cadavers revealed that this tendon is subject to mechanical bending and attrition, has no mesotenon and has a poorly vascularised portion about 5 mm in length, which may be a cause of spontaneous rupture of the tendon.

Adolescent↗

Consistently nonoverlapping distribution of epidermal growth factor receptors in adult human skin detected by various monoclonal antibodies.

We tested three monoclonal antibodies, Ab1, Ab2 and Ab3, against epidermal growth factor receptors (EGFR) of human A431 epidermal carcinoma cells. EGFR immunoreactive to Ab1 (EGFR1) were localized in basal cells, especially at the epidermal sweat duct ridges, suprabasal cells, the peripheral cell layer of the sudoriferous duct, outer root sheaths of hair follicles, hair bulbs and sebaceous glands in all cases. On the other hand, EGFR immunoreactive to Ab2 (EGFR2) and EGFR immunoreactive to Ab3 (EGFR3) appeared in about half of the cases. They were situated on granular layers of the epidermis, especially in skin covered by hair, endothelial cells and the superficial layer of the sudoriferous duct. These results indicate that EGFR takes multiple forms in normal human skin and in A431 cells and that the form depends on the type of cells in the skin.

Adult↗

Inactivation of cis-diamminedichloroplatinum (II) in blood by sodium thiosulfate.

The mode of inactivation of cis-diamminedichloroplatinum (II) (DDP) in the bloodstream by sodium thiosulfate (STS) was investigated experimentally and clinically by a bioassay system using the phytohemagglutinin stimulation assay of human peripheral blood mononuclear cells. Active DDP in the plasma of dogs after 3 mg/kg of DDP injection, assessed by the bioassay system, was almost completely inactivated, when the level of STS in the plasma was more than 500 times higher at molar STS/DDP ratios than that of DDP. In 6 patients with hepatic malignancies who were treated with hepatic artery infusion of 3 mg/kg DDP and systemic STS, active DDP in the plasma was not detectable in the concurrent presence of STS at molar ratios of more than 500. Severe DDP toxicity in these patients was completely protected. The results indicate that an inactivation of DDP in the bloodstream after DDP injection and, further, an effective protection against DDP toxicity can be achieved by the concurrent presence of STS at molar ratios of more than 500 in the plasma of these patients.

Animals↗

Clinical correlations with chemosensitivities measured in a simplified tritiated thymidine incorporation assay in patients with malignant effusion.

Utilizing a simplified tritiated thymidine incorporation assay, in vitro chemosensitivity of tumor cells obtained from malignant effusions was assessed and, in these patients, chemotherapeutic drugs were administered directly into the peritoneal or pleural cavity. Then, correlations between in vitro sensitivity and clinical response were investigated. Fifteen (88%) of 17 patients with various carcinomas gave evaluable chemosensitivity results. All 15 patients were evaluable for in vitro-in vivo correlations. This assay had an accuracy of 75% for prediction of response (3 of 4) and an accuracy of 82% for prediction of resistance (9 of 11), when the peak achievable plasma concentrations were selected as the concentrations used for in vitro sensitivity testing, adopting 80% inhibition of thymidine incorporation as cutoff level.

Adult↗