Biomedical subjects

H S Lin

Publications and source records attributed to H S Lin.

At least 73 records · Page 4Linked to original sources

PubMed1991

Effect of retinoids and carotenoids on prostaglandin formation by oral squamous carcinoma cells.

Several studies have correlated the excessive production of prostaglandins (PGs) with tumor promotion and the suppression of the immune response. Inhibition of PGs by pharmacological agents has been demonstrated to enhance immunocompetence, and to suppress growth of tumors in animals and humans. In this study we examined the effect of retinol (I), all-trans-retinoic acid (II), N-(4-Hydroxyphenyl) retinamide (N-4-HPR) (III), canthaxanthin (CTX) (IV), and beta-carotene (beta-CT) (V) on the bioconversion of 14C-arachidonic acid (AA) to PGE2 by squamous carcinoma cells of the tongue, SCC-25. Agents (I), (II), (III), (IV) inhibited while (V) stimulated PGE2 formation in a dose related manner. N-4-HPR was the most potent inhibitor of PGE2 synthesis. The data suggest that certain retinoids and carotenoids have the potential of inhibition of PG synthesis by oral squamous carcinoma cells. Inhibitory effects such as those described here and antioxidant properties might in part contribute to the antiinflammatory and anticarcinogenic activity of retinoids in vivo.

Canthaxanthin↗

PubMed1991

Ultrastructural localization of cytochrome oxidase and monoamine oxidase on microcylinders, a Long-Evans rat-specific mitochondrial inclusion.

The presence of a unique inclusion body, the microcylinder, in the intracristal space of mitochondria was previously reported in various types of cells from spotted rats of the Long-Evans strain, but was not found in cells of albino rats. The microcylinder is about 30 nm in diameter and of indefinite length, and is composed of six filamentous subunits surrounding a central one. We performed electron microscopic cytochemical studies on the cells of uriniferous tubules and the corpus striatum in normal spotted rats of the Long-Evans strain and albino rats of Wistar and Sprague-Dawley strains. On the basis of oxidative polymerization of 3, 3'-diaminobenzidine by cytochrome oxidase (CYO) an cupric ferrocyanide deposition by monoamine oxidase (MAO), microcylinders were demonstrated to exhibit activity of these enzymes. Reaction products of other mitochondrial enzymes, such as succinate dehydrogenase and lactate dehydrogenase, were not deposited on microcylinders. We conclude that microcylinders are rat strain-specific mitochondrial inclusions and consist of protein components, particularly containing the mitochondrial enzymes CYO and MAO.

Animals↗

PubMed1991

An immunocytochemical study of effects of light deprivation on prolactin cells in the adenohypophysis of the golden hamster.

Population ratio and morphology of prolactin cells were studied by employing immunohistochemical methods in the adenohypophysis of normal and experimental golden hamsters of both sexes at 16 weeks of age. Prolactin cells occupied 29% of the total adenohypophyseal cells in the intact males exposed to 14/10 h light/dark schedule. After stimulation of the pineal activity by binding or exposure of males to continuous darkness for eight weeks, prolactin cells became atrophic and were reduced in population to 17% and 13%, respectively. Pinealectomy prevented to some extent the effects of the above treatments; thus, prolactin cells constituted 27% in the pinealectomized and blinded hamsters, and 19% in the pinealectomized and darkness-treated group; and their morphology was comparable with that of the intact controls. Prolactin cells in the normal females were apparently larger in size and more numerous as compared with those of the normal males, comprising 47% of cell population in the anterior pituitary. In response to light deprivation, prolactin cells were atrophic with a diminished cytoplasm and decreased in cell number as reflected in the population ratio of 27% in the blinded and 21% in the darkness-treated groups. In pinealectomized females combined with binding or darkness-treatment, prolactin cells contained an abundance of secretory granules in the cytoplasm and maintained the population ratio comparable to that in the intact females. The present study revealed that light deprivation exerts an inhibitory effect on the secretory activity of prolactin cells and also causes hypoplasia of prolactin cells in the hamster adenohypophysis, the effects being mediated by the pineal gland.

Animals↗

PubMed1990

Growth factor-dependent regulation of transferrin receptor in proliferating and quiescent macrophages.

Transferrin receptor (TfR) expression in a population of murine macrophages was investigated during the colony-stimulating factor-1 (CSF-1)-induced proliferation and quiescence. Depletion of CSF-1 from the culture medium of bone marrow cell-derived macrophages (BMM) resulted in a simultaneous decrease in the total (cell surface + intracellular) amount of TfR and complete cessation of proliferating activity [( 3H]thymidine incorporation). The addition of CSF-1 to quiescent BMM resulted in a bimodal increase in surface TfR activity. A rapid but transient twofold increase only on the cell surface due to changes in the cycling of TfR was followed by a steady increase of total cellular TfR due to de novo synthesis. A similar transient increase in surface TfR was also induced by another hemopoietic colony-stimulating factor, GM-CSF, which is mitogenic for BMM. IL-3, which did not stimulate the clonal growth of these cells, failed to modulate surface TfR. In contrast to its effect on the cycling rate of TfR in quiescent cells, CSF-1 had little effect on the TfR distribution on proliferating BMM as well as on the J774 cells (a macrophage-like tumor cell line) despite the latter expressing high levels of CSF-1 receptor. This study showed that (i) cell surface modulation by growth factor is a function of state of cellular proliferation, and (ii) rapid changes in the cell surface distribution of TfR result from changes in its cycling rates.

Animals↗

PubMed1990

Non-peptide angiotensin II receptor antagonists discriminate subtypes of 125I-angiotensin II binding sites in the rat brain.

We have utilized quantitative autoradiography to define subtypes of 125I-angiotensin II (AII) binding in rat brain. AII-1 binding (displaced by DuP 753) was found in the nucleus of the solitary tract and the hypothalamus, while AII-2 binding (displaced by WL 19) was found in the thalamus and lateral septum. These results indicate that subtypes of the AII receptor are present in the brain and the AII-1 receptor subtype is present in regions consistant with the known actions of angiotensin.

Angiotensin II↗

PubMed1990

The treatment of progressive non-Hodgkin's lymphoma with intensive chemoradiotherapy and autologous marrow transplantation.

Intensive chemoradiotherapy, with or without additional local radiotherapy, and unpurged autologous marrow transplantation was given to 68 patients with progressive non-Hodgkin's lymphoma. Responses were attained in 44 patients (65%, 95% confidence intervals [CI], 52% to 76%), including 37 who achieved complete responses. Fifteen patients (22%, 95% C.I. 13% to 34%) remain free of disease (including 11 continuously) at a median of 5.3 (range 3.1 to 9.1) years later. Higher Karnofsky scores (P less than .01, Mann-Whitney U test) and the absence of a history of prior radiotherapy (P = .02, chi 2 test) were associated with achievement of complete plus partial responses. Higher Karnofsky scores (P less than .01, Mann-Whitney U test) and less resistant disease status at transplantation (P = .04, chi 2 test) were significant when calculations were limited to complete responses. Karnofsky scores were also associated with the probability of freedom from progression (P = .02, log-rank) for responding patients. Also, Karnofsky scores and the absence of prior radiotherapy (P less than .01 and P = .01, respectively, log-rank) were associated with improved survival. Progressive lymphoma was the chief cause of failure; progression usually occurred less than 6 months after transplantation, most often at the sites of active disease before the transplant. However, five patients (including four with high-grade non-Hodgkin's lymphoma) suffered hematogenous patterns of relapse; four of these five patients had no prior history of marrow involvement. Other causes of mortality included interstitial pneumonitis, sepsis, hemorrhage and renal failure. Intensive chemoradiotherapy and autologous marrow transplantation produces durable remissions in some patients with progressive non-Hodgkin's lymphoma. Since such therapy is more effective when given to patients with signs of less advanced disease, earlier treatment would be the simplest way to produce improved results. However, improved conditioning regimens will also be needed, and measures to reduce occult lymphoma stem cell contamination with the autograft may also be required to increase the likelihood of cure in some patients.

Adolescent↗

PubMed1990

An immunoelectron microscopic study of corticotrophs in the golden hamster.

The ultrastructure of corticotrophs in the pituitary of golden hamsters was studied by immunocytochemistry. Corticotrophs were classified into three types according to the different size of the secretory granules. Type A and B cells were oval or polygonal in shape containing small (158 +/- 38 nm) and medium-sized (250 +/- 53 nm) secretory granules, respectively. Type C cells were usually pyramidal or irregular in shape, and contained large secretory granules (380 +/- 78 nm). The cytoplasmic organelles of type B and C cells were fairly well developed. In all types of corticotrophs, the secretory granules varied in electron density, and were either arranged in a single row along the cell membrane, or concentrated in the vascular pole of the cytoplasm. Many of the corticotrophs sent processes to encircle neighboring somatotrophs. In the female, the proportions of type A and B cells were higher than those in the male, whereas that of the type C cells was lower. All three types of corticotrophs were observed in the early postnatal stage. The population of type A cells decreased with the advancement of postnatal development, with a concomitant increase of that of the type C cells. Thus, type A cells might represent the immature type of corticotrophs which would evolve to become the type C cells. One to 2 weeks after adrenalectomy, the number of type C cells was drastically increased. This was accompanied by their prominent changes in ultrastructure as in the type B cells. The cytoplasm became hypertrophic with extensive dilated cisternae of rough endoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1990

Comparison of the inhibitory effect of polyunsaturated fatty acids on prostaglandin synthesis. II. Fibroblasts.

In a previous publication we reported that PUFAs of the n-6 and n-3 series caused significant inhibition of synthesis of both PGE2 (28.4-92.8%) and PGF2 alpha (24.4-84.0%) in the oral squamous carcinoma cell line SCC-25. In this report we describe the inhibitory effect of the same acids on PG synthesis in normal human gingival fibroblasts under the same experimental conditions. It was found that a combination of EPA + DCHA (6:4), DCHA and ALA caused significant reduction in synthesis of PGE2 (10.1-87.8%) and PGF2 alpha (14.0-54.6%) at the four dose levels studied. The rank order of potency of acids in reduction of PG synthesis was: EPA + DCHA greater than DCHA greater than EPA greater than ALA greater than LA greater than DGLA greater than GLA. The data suggest that although PUFAs are effective inhibitors of PG synthesis by gingival fibroblasts and SCC-25, the fibroblast is less susceptible to the inhibitory effect of fatty acids.

Adult↗

PubMed1990

In vitro inhibition of prostaglandin biosynthesis in squamous cell carcinoma by retinoids.

The aim of this study was to evaluate the effect of four natural and synthetic retinoids: Ro 12-7310 (I), Ro 13-7410 (II), 13-cis-retinoic acid (III), and Ro 13-7652 (IV) on the synthesis of PGE2 in human squamous cell carcinoma (SCC) of the tongue (SCC-25). 5 X 10(6) cells were plated and labeled with 0.2 microCi of (14C)-arachidonic acid (AA) in 2 ml of DMEM/F12 containing 0.1% BSA for 4 h. The cells were then washed, and incubated in serum-free medium with the retinoids (10,20,30,40 microM) for 1 h. The cells were further stimulated with melittin an additional hour. Radioactive metabolites released in media were then extracted with diethyl ether. The ether extracts were separated by TLC and radioactive PGE2 zone was quantitated by means of liquid scintillation counting. The rank order of percent inhibition of PGE2 synthesis by retinoids at four concentration levels was (I) greater than (II) greater than (III) greater than (IV). Since inhibition of PG production has been demonstrated to suppress growth of tumors in animal models and humans, further study on the effect of retinoids on growth of SCC in vitro as well as in vivo seems warranted.

Acitretin↗

PubMed1989

A sandwich enzyme-linked immunoadsorbent assay for detection of murine macrophage colony-stimulating factor (CSF-1).

A simple three-layer sandwich enzyme-linked immunoadsorbent assay (sandwich-ELISA) has been developed for murine macrophage colony-stimulating factor-1 (CSF-1) using the two monoclonal antibodies on which we recently reported (J. Immunol. (1988) 141, 483). The anti-CSF-1 monoclonal antibodies used in this assay recognize different epitopes of the same antigen, thereby permitting the detection of low amounts of CSF-1. This assay is specific to murine CSF-1. Recombinant human macrophage colony-stimulating factor, murine GM-CSF, or IL-3, either alone or together with CSF-1, does not interfere with the assay. The advantage of this assay over other reported immunoassays for CSF-1 is that radiolabeled or large quantities of purified CSF-1 are not required. This sandwich-ELISA compares favorably with other assays in its rapidity, simplicity, and sensitivity.

Animals↗

PubMed1989

Both granulocyte-macrophage CSF and macrophage CSF control the proliferation and survival of the same subset of alveolar macrophages.

The effect of granulocyte-macrophage (GM)-CSF on the proliferation of murine pulmonary alveolar macrophages in vitro was investigated. About 20% of freshly isolated alveolar macrophages formed colonies in both liquid and soft agar cultures in the presence of GM-CSF. GM-CSF was also found to be capable of maintaining the survival of these colony-forming cells in vitro. Moreover, GM-CSF could substitute for CSF-1 in maintaining the survival of CSF-1-responding pulmonary alveolar macrophage colony-forming cells in the absence of CSF-1. The concentration of GM-CSF required for maintaining the survival of colony-forming cells without proliferation was much lower than that required for the proliferation of these cells in vitro. It also enhanced the CSF-1-dependent clonal growth of alveolar macrophages. These data suggest that the colony-forming cells that respond to GM-CSF are the same subset of macrophages that form colonies in the presence of CSF-1. GM-CSF did not inhibit the binding of 125I-CSF-1 to alveolar macrophages at 0 degrees C. However, the preincubation of macrophages with GM-CSF at 37 degrees C resulted in a transient down-regulation of CSF-1 binding activity.

Animals↗

PubMed1989

Regulation of systemic macrophage IL-1 gene transcription: the involvement of tumor-derived macrophage growth factor, CSF-1.

Previous data indicated that progressive growth of the C57BL/6J sarcoma, MCA/76-9, was associated with a systemic increase in the level of IL-1 activity in peritoneal and tumor-associated macrophages. In this paper, the hypothesis was tested that macrophage IL-1 alpha and beta gene expression was regulated by the specific macrophage growth factor, CSF-1, produced by tumor cells. The data indicated that all of the nine C57BL/6J, BALB/cJ, and C3H/HeJ sarcomas tested transcribed the CSF-1 gene. The tumor cell culture supernates induced proliferation of bone marrow cells that differentiated into macrophages. Moreover, proliferative activity of conditioned medium and the ability to induce macrophage differentiation were abrograted by neutralization with the 5A1, rat-anti-mouse monoclonal anti-CSF-1 antibody. Conditioned medium from tumor cell cultures, as well as recombinant CSF-1 and L cell-conditioned medium, induced transcription of the IL-1 alpha and beta genes, the latter being more strongly expressed. IL-1 gene transcription was not induced after neutralization of the culture supernates by the monoclonal antibody, 5A1. The overall data would support the hypothesis that the pathway in vivo leading to the increased IL-1 expression by macrophages is regulated by at least one tumor cell product, CSF-1.

Animals↗

PubMed1989

Purification and characterization of a benzodiazepine-like substance from mammalian brain.

An endogenous brain ligand which competes with [3H]-flunitrazepam for the binding to benzodiazepine receptor has been isolated and purified to homogeneity. The purification procedures involve the extraction of the endogenous ligand by homogenizing the brain tissue in water containing various protease inhibitors followed by filtration through a PM 10 membrane (exclusion limit: 10,000-dalton), column chromatographies on Sephadex G-50, Bio-Rad P2 and a series of C18 reverse phase HPLC columns. The purified endogenous ligand was eluted as a single and symmetrical peak monitored at either 220 or 280 nm. Furthermore, the ligand activity coincided with the absorption peak. The purified endogenous ligand is thermostable, insensitive to various peptidases and proteolytic enzymes, resistant to DNAse, RNAse, and carbohydrate enzyme e.g. neuraminidase (EC 3.2.1.18) and acid treatment. It has a major absorption peak at 220 nm and a minor one at 313 nm. The endogenous ligand appears to be quite specific since it only inhibits the binding of ligand to the central type benzodiazepine receptor but not to other receptors, e.g. peripheral type benzodiazepine receptor, alpha 1-adrenoceptor, alpha 2-adrenoceptor, beta-adrenoceptor and muscarinic cholinergic receptor. Furthermore, the inhibition of the receptor binding by the endogenous ligand is enhanced by GABA suggesting that the endogenous ligand is a benzodiazepine receptor agonist. The structure of the endogenous ligand is unknown.

Animals↗

PubMed1989

Comparison of the inhibitory effect of polyunsaturated fatty acids on prostaglandin synthesis I oral squamous carcinoma cells.

Polyunsaturated fatty acids (PUFAs) have been shown to suppress the growth rate of human osteogenic sarcoma cells and to have selective cytotoxic activity against human cancer cells. The purpose of this study was to investigate the efficacy of various PUFAs on inhibition of prostaglandin (PG) synthesis by oral squamous carcinoma cells (SCC-25). A significant inhibition of PGE2 and PGF2 alpha synthesis in SCC-25 was observed by all PUFAs tested except in the case of linoleic acid (LA) at 10 microM level. At 10 microM level the rank order of inhibition of PG synthesis by PUFAs was docosahexaenoic (DHA) greater than eicosapentaenoic (EPA) + DHA greater than dihomogamma-linolenic (DGLA) greater than EPA greater than alpha-linolenic (ALA) greater than linoleic (LA). At 50, 75, 100 microM the rank order of inhibition was DGLA greater than EPA greater than EPA + DHA greater than DHA greater than ALA greater than LA.

Administration, Oral↗

PubMed1989

Unusual ultrastructural features in the superficial pineal gland of the yellow-bellied country rat (Rattus losea Swinhoe).

The ultrastructure of the superficial pineal gland of the yellow-bellied country rat (Rattus losea Swinhoe), living under natural climatic conditions at the margin of the tropical region, was studied with special reference to the seasonal changes. In the rainy season with average monthly rainfall of 400 mm (light phase of 13.5 h, and temperature of 28 degrees C) the gland was characterized by the presence of frequent large vacuoles containing flocculent material (LVFs), large condensed inclusions (LCIs) in the pinealocytes, and extensive accumulations of presumptive secretion in the extracellular compartment, suggesting an enhanced secretory activity. In the dry season with average monthly rainfall of 13 mm (light phase of 11 h, and temperature of 19 degrees C), however, the pinealocytes were characterized by the presence of numerous clear spindles, which exhibited acid phosphatase activity; at this time there were few LVFs and LCIs and rare extracellular accumulations, suggesting a declined glandular activity. We conclude that the cellular activity of the pineal gland in R. losea, living under tropical climatic conditions, is synchronized with the annual changes of rainfall, which is apparently more important than the annual changes of photoperiod and temperature.

Animals↗

PubMed1989

A unique microvesicular sphere associated with the Golgi complex of gonadotrophs in the golden hamster.

A spherical accumulation of numerous, closely packed, minute vesicles, tentatively called a microvesicular sphere (MVS), was often found at the cis side of the Golgi complex in the gonadotroph of the hypophysis of the golden hamster. After prolonged impregnation with OsO4, the cis saccules of the Golgi stack and the MVS were stained with osmium. In gonadotrophs from normal and castrated hamsters, reaction products of thiamine pyrophosphatase (TPPase) and inosine diphosphatase (IDPase) were intensively localized in the trans and intermediate cisternae of the Golgi complex, respectively, but not in the MVS. Acid phosphatase (AcPase) reaction products were patchily distributed in the trans cisternae of the Golgi stack, but were not localized in the MVS in normal and castrated hamsters. However, in the blinded hamsters, in which gonadotrophs and their Golgi complexes were atrophic, AcPase reaction products were seen consistently in the MVS, and also in many of the Golgi cisternae in addition to those on the trans side. In such cells TPPase and IDPase activities were greatly decreased; the endoplasmic reticulum and Golgi complexes might be engaged in production of lysosomal proteins rather than secretory products. The MVS may represent an accumulation of special transfer vesicles between the endoplasmic reticulum and the Golgi complex, and may constitute an adjunct of the latter in certain cell types.

Animals↗

PubMed1989

Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation.

Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease-free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.

Adolescent↗

PubMed1989

Biochemical mechanisms underlying the development of radioresistance by cultured peritoneal exudate macrophages.

We investigated changes in radiosensitivity of peritoneal exudate macrophage colony-forming cells (PE-CFC) when exudative peritoneal macrophages were cultured in vitro. The change in the shape of the dose-response curve of PE-CFC to ionizing irradiation was partly dependent on the concentration of oxygen in the gas phase of the incubators. When cells were incubated in an environment containing 20% oxygen, the value of both Dq and D0 for PE-CFC increased. The dose-response curve of PE-CFC cultured for 3 days resembled that of alveolar macrophage colony-forming cells (AL-CFC). The changes in radiosensitivity were accompanied by an increase in the level of three antioxidant enzymes: superoxide dismutase, catalase, and glutathione peroxidase. However, when they were cultured in a 6% oxygen environment, only the value of Dq increased. When alveolar macrophages were incubated in vitro, no significant change in the shape of the dose-response curve of AL-CFC was noted whether they were cultured in gas phase containing either 20 or 6% oxygen. It is concluded that the radiosensitivity of PE-CFC changes when they are cultured in vitro. The increase in D0 appears to be related to the intracellular level of antioxidant enzymes.

Animals↗