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Biomedical subjects

J K Chen

Publications and source records attributed to J K Chen.

At least 109 records · Page 6Linked to original sources

Mitogenic response of rat Schwann cells to fibroblast growth factors is potentiated by increased intracellular cyclic AMP levels.

Rat sciatic nerve Schwann cells either do not proliferate, or proliferate very slowly, in medium containing 10% fetal bovine serum (FBS). They were previously shown to respond only to a limited number of mitogens associated with cells of central and peripheral nervous systems, which appeared to be distinct from FGFs and PDGF, and to agents that raise intracellular cAMP levels. In a basal medium consisting of 75% DMEM, 25% Ham's F-12, 5 nM sodium selenite, 50 microM 2-amino ethanol, and 2 mM histidine, supplemented with 5% FBS, we showed that aFGF, bFGF, and PDGF were all capable of stimulating Schwann cell growth and the stimulation was greatly potentiated by forskolin and dibutyryl-cAMP. In addition, pretreating culture surface with purified matrix proteins such as laminin, fibronectin, or type 1 collagen, was necessary for obtaining a better cellular response to the mitogenesis of these growth factors even in 10% FBS. Our results clearly indicated that providing a suitable medium and substratum, aFGF, bFGF and PDGF are mitogens for rat sciatic nerve Schwann cells in medium with and without forskolin or dibutyryl-cAMP.

Animals↗

Stimulation of human arterial smooth muscle cell chondroitin sulfate proteoglycan synthesis by transforming growth factor-beta.

Human platelet-derived transforming growth factor-beta (TGF-beta) is a cell-type specific promotor of proteoglycan synthesis in human adult arterial cells. Cultured human adult arterial smooth muscle cells synthesized chondroitin sulfate, dermatan sulfate, and heparan sulfate proteoglycans, and the percent composition of these three proteoglycan subclasses varied to some extent from cell strain to cell strain. However, TGF-beta consistently stimulated the synthesis of chondroitin sulfate proteoglycan. Both chondroitin 4- and chondroitin 6-sulfate were stimulated by TGF-beta to the same extent. TGF-beta had no stimulatory effect on either class of [35S]sulfate-labeled proteoglycans which appeared in an approximately 1:1 and 2:1 ratio of heparan sulfate to dermatan sulfate of the medium and cell layers, respectively, of arterial endothelial cells. Human adult arterial endothelial cells synthesized little or no chondroitin sulfate proteoglycan. Pulsechase labeling revealed that the appearance of smooth muscle cell proteoglycans into the medium over a 36-h period equaled the disappearance of labeled proteoglycans from the cell layer, independent of TGF-beta. Inhibitors of RNA synthesis blocked TGF-beta-stimulated proteoglycan synthesis in the smooth muscle cells. The incorporation of [35S]methionine into chondroitin sulfate proteoglycan core proteins was stimulated by TGF-beta. Taken together, the results presented indicate that TGF-beta stimulates chondroitin sulfate proteoglycan synthesis in human adult arterial smooth muscle cells by promoting the core protein synthesis.

Adult↗

Cultured vascular endothelial cells secrete a protein factor(s) that promotes the contraction of collagen lattices made with fibroblasts.

Conditioned media collected from arterial endothelial cells contain protein factor(s) that promotes the contraction of collagen lattices made with skin fibroblasts. Based on the lattice contraction-promoting activity, a protein with an apparent molecular weight of 22 kDa was identified. This 22-kDa protein stimulated lattice contraction in both serum-containing and serum-free media. When assayed at a 30% equivalent of the conditioned medium, the contraction-promoting activity of the purified factor was about 50 to 60% of that elicited by the unfractionated conditioned medium. Some contraction-promoting activity was also present in certain subfractions of the conditioned medium generated during the separation of the 22-kDa protein. Taken together, the results indicate that the lattice contraction-promoting activity in the endothelial cell-conditioned medium is probably aided by multiple active principles. The biochemical and biological characteristics indicated that the 22-kDa protein is not a transforming growth factor-beta-related factor nor a fibroblast growth promoter.

Chromatography, High Pressure Liquid↗

Changing trends in oral cancer in the United States, 1935 to 1985: a Connecticut study.

An extensive epidemiologic study was undertaken in an attempt to analyze patterns of oral cancer distribution and demography in Connecticut between 1935 and 1985. Sources of data for the investigation included both the Connecticut Tumor Registry (CTR) and the University of Connecticut Oral Pathology Biopsy Service. During the 51-year study period, 9,708 cases of primary oral cancer were reported to the CTR. Male age-adjusted incidence rates for overall oral cancer remained stable between 1935 and 1964 (14.5 to 14.8 per 100,000), with a gradual decline to 10.9 per 100,000 in the early 1980s. In contrast, age-adjusted rates for females advanced approximately threefold, from 1.4 per 100,000 in the 1930s to 4.1 per 100,000 in the early 1980s. There was a decrease in age-specific rates of oral cancer in males aged 70 and older; in contrast, age-specific incidence rates in females increased steadily over the same period. It was also found that female birth cohorts born in 1900 and later exhibited higher oral cancer incidence rates than those of previous cohorts. Between the 1960s and the present, male patients 30 to 39 years of age exhibited a nearly fourfold increase in oral cancer incidence; this was not observed among similarly aged females. Connecticut counties with highest oral cancer incidence rates in both sexes were the more densely populated Hartford and New Haven counties. In general, the picture of oral cancer, as revealed through analysis of cases accessioned by the University biopsy service between 1975 and 1986, exhibited similar trends to those disclosed by analysis of CTR data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Localization of bone sialoprotein (BSP) expression to sites of mineralized tissue formation in fetal rat tissues by in situ hybridization.

Bone sialoprotein (BSP) is a major protein in the mineralized matrix of bone and dentine. To study the relationship between the expression of BSP and the formation of mineralized connective tissues, a cDNA probe to rat BSP was prepared for in situ hybridization analysis of developing fetal rat bones and teeth. When used for Northern hybridization analysis of rat bone marrow cells induced to differentiate into osteogenic cells by dexamethasone, the BSP cDNA revealed a specific induction of 1.6- and 2.0-kb mRNA species of BSP. In tissue sections a strong hybridization signal associated with osteoblasts was observed in areas of endochondral bone formation in the long bone metaphysis and condylar cartilage, and in the intramembranous bone of the calvaria and mandible. Hybridization reflecting a lower degree of expression was evident in cells of the transitional zone of mineralizing cartilage and in odontoblasts forming incisor dentine. Expression of BSP was also demonstrated in the hypertrophic cartilage cells in the long bone and condylar process. In contrast, expression of BSP could not be detected in the reserve or proliferative chondrocytes, fibroblasts and muscle cells. These studies demonstrate that the expression of BSP in bones and teeth is essentially restricted to cells directly involved in the formation of mineralizing connective tissue matrices, indicating that BSP has a specific role in biological mineralization and that it is a useful marker of bone formation.

Animals↗

Intraoral squamous cell carcinoma. Epidemiologic patterns in Connecticut from 1935 to 1985.

There were 6181 cases of invasive intraoral squamous cell carcinoma accessioned by the Connecticut State Tumor Registry from 1935 to 1985. Cases were analyzed for age, sex, lesion site, and histologic differentiation. Crude, age-specific, and age-adjusted incidence rates plus birth cohort analyses were also calculated. It was found that incidence rates for both men and women increased over the 51-year period of study. For men, age-adjusted incidence rates (1970 United States standard) increased from 4.9/100,000 in 1935 to 1939 to 8.5/100,000 in 1980 to 1985; for women, rates increased from 0.5/100,000 to 3.3/100,000 for the same period. The male-to-female ratio for intraoral squamous cell carcinoma declined dramatically from 9.8 to 2.6 during the 51-year study period primarily because of the steep rate of increased incidence in women relative to that seen in men. The peak age of intraoral squamous cell carcinoma was the seventh decade. Age-specific analysis showed that the older the age group, the higher the incidence for both sexes. During recent years, there was evidence of slightly increased incidence in men younger than 40. The tongue was the most common site for intraoral squamous cell carcinoma, followed closely by the floor of the mouth. Moderately differentiated tumors were most common (54.3% of the total), followed by both well-differentiated cases (29.1%) and those that were poorly differentiated (16.6%).

Adult↗

Epidemiology of oral cancer in Connecticut, 1935 to 1985.

All cases of oral cancer (N = 9708) recorded by the Connecticut Tumor Registry from 1935 to 1985 were analyzed for time-trend patterns within 10-year age-groups. Crude, age-specific, age-adjusted incidence rates and birth cohort analyses were calculated. The average annual age-adjusted incidence rate was 12.9/100,000 for men and 2.9/100,000 for women (1970 US standard million population). The male age-adjusted incidence rate decreased 33% from the late 1930s to the early 1980s. The female age-adjusted incidence rate exhibited a threefold steady increase over this same time period. The male/female ratio for oral cancer incidence declined dramatically from 10.4 to 2.7 for the age-adjusted rate, nearly a fourfold decrease during the 51- year period. Birth cohort analyses for women indicated a marked increase in oral cancer incidence for the birth cohort of 1900, which was sustained in the birth cohorts that followed. Birth cohort analyses for men revealed a decline in oral cancer incidence for birth cohorts born after 1910. The highest incidence rates were found in the urban counties and the lowest in the rural areas.

Adult↗

TGF-beta inhibits the platelet-derived growth factor-induced formation of inositol trisphosphate in MG-63 human osteosarcoma cells.

Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and heparin-binding growth factor-1 (HBGF-1) stimulated the proliferation of a variant of the human osteosarcoma cell line, MG-63-LS (LS = low serum). Transforming growth factor beta (TGF-beta) completely inhibited cell growth in basal medium supplemented with 2% fetal calf serum (FCS), blocked PDGF- and EGF-stimulated cell proliferation, and modulated that of HBGF-1. PDGF, but not EGF or HBGF-1, activated the inositol trisphosphate/diacylglycerol (IP3/DAG) second message system in a dose-dependent manner. EGF inhibited phosphoinositol lipid turnover and HBGF-1 and TGF-beta stimulated phosphatidylinositol hydrolysis to produce inositol phosphate (IP) but not IP3. Preincubation of quiescent cells with TGF-beta for 30-40 minutes prior to the addition of PDGF resulted in an inhibition of PDGF-induced production of IP3. This suggested that TGF-beta was an indirect inhibitor and blocked PDGF-stimulated cell growth in part by interfering with the generation of the second messenger, IP3.

Cell Division↗

A pharmacodynamic and pharmacokinetic study of the Chinese No. 1 pill.

A pharmacodynamic and pharmacokinetic study of the Chinese No. 1 pill, a combined oral contraceptive containing 35 micrograms ethynyloestradiol (EE) and 600 micrograms norethisterone (NET), was performed in 29 women over a period of six months. Blood samples for analysis were taken during a pretreatment cycle, the first and 6th treatment cycles and post-treatment. Minor changes in carbohydrate metabolism occurred and these were particularly noticeable when the incremental areas under the serum concentration-time curves for both glucose and insulin in response to a glucose tolerance test were calculated. No changes occurred in the serum glycosylated haemoglobin levels. The serum concentrations of all the lipids measured (total cholesterol, triglycerides, LDL-C, HDL-C and apolipoproteins AI, AII and B) were significantly increased on treatment as were levels of Factor X, SHBG and caeruloplasmin whereas antithrombin III decreased. In 38 of the 40 treatment cycles, ovulation was suppressed. In one cycle serum oestradiol and progesterone levels showed a typical ovulatory pattern and in another there was evidence of follicular activity without ovulation. Serum EE concentrations showed a similar pattern in both treatment cycles showing that co-administration of NET did not affect EE metabolism. Serum NET levels were higher in the 6th than in the first treatment cycles. On comparing pharmacodynamic and pharmacokinetic parameters, the only statistically significant correlations were between the percentage change in triglycerides and SHBG and serum NET, but not EE concentrations, and between apolipoproteins AI and serum EE.

Adult↗

Oral cancer: a survey of 566 cases from the University of Connecticut Oral Pathology Biopsy Service, 1975-1986.

A survey of the University of Connecticut Oral Pathology Biopsy Service was undertaken to analyze cases of oral cancer accessioned during the 12-year period, 1975 through 1986 inclusive. Of 33,429 total specimens accessioned, there were 546 malignant oral neoplasms diagnosed and reported. Sixty-five (11.5%) originated from out of state. Invasive intraoral squamous cell carcinoma was the predominant tumor (69.7% of total), whereas lip cancer constituted only 2.8% of all malignancies. Minor salivary gland adenocarcinomas accounted for 11% of total malignancies whereas verrucous carcinoma, carcinoma in situ, and miscellaneous other forms of oral cancer accounted for the remainder (4.6%, 5.3%, and 6.6%, respectively). Cases of invasive squamous cell carcinoma were further analyzed by year, sex distribution, location subsite, age at diagnosis, and histologic grade. With the exception of histologic grading, we found that the characterization of cases of squamous cell carcinoma within the biopsy service tended to parallel results from a separate but related statewide analysis of both oral cancer and intraoral squamous cell carcinoma from Connecticut over a much longer time span. We concluded that the picture of oral cancer as characterized by cases within the University of Connecticut Oral Pathology Biopsy Service is generally reflective of the disease on a statewide level.

Adult↗

Induction of morphological transformation by coal-dust extract in BALB/3T3 A31-1-13 cell line.

The transforming activity of coal dust extracts was studied using BALB/3T3 clone A31-1-13 cells. Coal-dust extracts, both nitrosated and nonnitrosated, induced cell transformation in a dose-response manner. However, the transformation frequency was higher with the nitrosated than with the nonnitrosated extract. All transformed cell lines derived from coal-dust extract-induced foci showed biological characteristics of neoplastic transformation such as loss of contact inhibition and anchorage-independent growth. These results appear to support a hypothesis of coal mine dust causation of gastric cancer in coal miners.

Animals↗

[Condition to produce oscillation after twitch shortening in the bullfrog geniohyoid muscle].

Two different types of elastic behaviors could be distinguished in the twitch contraction curve of the isolated frog geniohyoid muscle under changing of chemical conditions; one was negative oscillation that occurred after completion of the relaxation phase which was sequential to a typical cyclic pattern demonstrated in the contraction and relaxation period, and the other was oscillation which occurred in the phase of plateau formation during relaxation. The former will relate to the parallel elastic component (the effect of caffeine combined with a low Ca++ condition) and the latter will to the series one (collagenase and dantrolene). The causal or genetic relationship is not yet clarified.

Animals↗

[CT scans in the diagnosis of cerebellar hemangioblastomas. Analysis of 21 cases].

Computed tomography (CT) scans in 21 patients with pathological verified cerebellar hemangioblastoma were analysed. There were 14 cases of cystic nodular pattern, 4 cases of nodular pattern and 3 cases with the pattern of cyst only in this series. The characteristic features of hemangioblastomas on the CT scans usually consisted of large circumscribed cystic low density lesions with a small enhanced nodule in each of them. On surgical operations 20 cases in this series were classified to be of cystic-nodular pattern. In order to show the cystic-nodular pattern in a better manner on the CT the thin slice CT scan 5 should be recommended in addition to the use of an appropriately increases amount of intravenous contrast medium when hemangioblastoma of the cerebellum would be suspected.

Adolescent↗

[One possible mode of protective actions of mucin in the digestive canal].

This report describes an additional fact indicating the protective action of mucopolysaccharide in the digestive canal. Roughly speaking, the living organism is composed of structural and functional (physiologically active) substances. Through experimental observations, we have now got the theoretical idea that a functional substance not only possesses a proper inherent activity but has acquired new accessory activities during developmental course. For example, as shown in the previous papers, the authors have revealed that mucin, which is originally an intensive lubricant to make or to transfer the bolus, can be an agent to initiate, maintain or promote the spontaneous movement of the isolated intestinal strip. In this paper, when acetylcholine is applied to the bathing solution of the strip together with eserine, its promotive effect on the spontaneous movement is abolished by mucin probably because of direct binding which renders acetylcholine ineffective.

Acetylcholine↗

[The changes of integrated water response waves of frog tongues by divalent cations (Ca++, Mg++, Ba++, etc.)].

In the frog tongue, there is an interesting physiological phenomenon named water response. Accordingly, it is said that the frog gustatory nerve contains water fiber. In spite of much experimental data, the nature or establishing process of water response is now not yet clear. As a common process the enhancement effect of Ca++ on the water response is well known. Standing on this idea, the authors have comparatively investigated the effects of Ca++, Mg++, Ba++, and Sr++ which are all divalent ions on the integrated wave form of water response. Original water response (integrated wave form) was simply enhanced in height and width by Ca++. The effect of Sr++ was qualitatively and quantitatively very similar to the effect of Ca++. Mg++ suppressed the water response especially in the beginning phase. Ba++ first suppressed the height of water response but, after repetition of experimental procedure, sufficient size of water response was achieved. As far as the effect on the water response form, some are similar but some are different. It is conclusively supposed that the conditions which permit the release or removal of the tissue Ca++ are the conditions which render the water response larger, and vice versa.

Animals↗

Differential inhibitory effects of TGF-beta on EGF-, PDGF-, and HBGF-1-stimulated MG63 human osteosarcoma cell growth: possible involvement of growth factor interactions at the receptor and postreceptor levels.

The growth of MG63 human osteosarcoma cell line in 5% serum is stimulated by epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or heparin-binding growth factor-1 (HBGF-1). The mitogenic effect of EGF and PDGF is completely blocked by TFG-beta at 1 ng per ml and the effect of HBGF-1 is attenuated by 75-80%. Treatment of MG63 cells with TGF-beta reduces HBGF-1 receptor binding affinity from 1.24 x 10(-11) M to 3.51 x 10(-11) M with no change on the receptor number (1.1 x 10(3) per cell). The receptor-binding affinity of EGF and PDGF is not altered by TGF-beta treatment; however, the number of EGF receptor is increased by 25%. Both EGF and PDGF stimulate MG63 cellular tyrosine kinase activity, and such stimulation is inhibited by TGF-beta pretreatment. No change in the cellular protein tyrosine phosphorylation pattern can be detected in HBGF-1-stimulated cells with and without TGF-beta pretreatment. These data suggest that TGF-beta inhibits EGF and PDGF mitogenicity by blocking EGF- and PDGF-stimulated tyrosine kinase activity and attenuates HBGF-1 mitogenicity by decreasing its receptor affinity.

Cell Division↗

Transforming growth factor-beta inhibits cellular adenylate cyclase activity in cultured human arterial endothelial cells.

Stimulation of human arterial endothelial cells with heparin-binding growth factor-1 (HBGF-1) resulted in a 40% to 60% increase in the cellular adenylate cyclase activity and intracellular cAMP content. The stimulatory effect of HBGF-1 was effectively suppressed by pretreating the cells with transforming growth factor-beta (TGF-beta), an endothelial cell growth inhibitor. The inhibition of the adenylate cyclase activity precedes growth inhibition by at least 24 h. The half maximal inhibitory dose was calculated to be 0.2 ng/ml for the inhibition of both cyclase activity and cell growth. The possible role of the adenylate cyclase suppression in growth inhibition by TGF-beta is discussed.

Adenylyl Cyclase Inhibitors↗

Effect of some oral contraceptives on serum concentrations of sex hormone binding globulin and ceruloplasmin.

Serum SHBG and ceruloplasmin (CP) concentrations were measured in women throughout a cycle of treatment with four oral contraceptives. In women receiving 150 micrograms levonorgestrel (LNG) daily both SHBG and CP decreased. SHBG also decreased, but CP increased, in women receiving ethynyloestradiol (EE) 30 micrograms with LNG 150 micrograms. In women taking 35 micrograms EE with either 600 micrograms or 1000 micrograms norethisterone, increases in CP were similar but SHBG increased more with the lower dose. Serum concentrations had not returned to pretreatment levels by eight days after cessation of dosing. The findings are compared with similar results for women taking 30 micrograms or 50 micrograms EE or an EE,LNG triphasic formulation. Serum concentrations of the gestagens were also measured. Increases in these concentrations when the gestagen was administered with EE to levels higher than expected from administration of the gestagen alone cannot be explained by increased binding to SHBG but are more likely to be due to changes in their metabolism. Differences in the responses of ostensibly closely related proteins of hepatic origin such as SHBG and CP to the oral contraceptives demonstrate that neither can be extrapolated to other pharmacodynamic responses.

Adult↗