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Biomedical subjects

F Chang

Publications and source records attributed to F Chang.

At least 91 records · Page 5Linked to original sources
PubMed1994

Actions of vasoactive intestinal peptide and neuropeptide Y on the pacemaker current in canine Purkinje fibers.

We have investigated the actions of vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) on the pacemaker current (I(f)) in canine Purkinje fibers. On voltage pulses to the middle of the I(f) activation range, VIP reversibly increases I(f), whereas NPY reversibly decreases I(f). A three-pulse voltage protocol suggests that VIP shifts I(f) activation in the positive direction and that NPY shifts I(f) activation in the negative direction on the voltage axis without changing maximal I(f) conductance. These effects of VIP and NPY on I(f) are exerted through their specific peptide receptors, since the effects are blocked by VIP and NPY receptor antagonists. VIP and NPY are colocalized in cardiac parasympathetic and sympathetic nerve endings, respectively, and can be released preferentially on high and long-lasting nerve stimulation. Given this colocalization and frequency-dependent release, these results suggest a role for these neuropeptides in controlling cardiac I(f) and consequently heart rate.

Animals↗
PubMed1993

Screening for human papillomavirus infections in esophageal squamous cell carcinomas by in situ hybridization.

BACKGROUND: Infections with specific types of human papillomavirus (HPV) have been closely linked with human squamous cell carcinomas, those of the anogenital tract in particular. Increasing number of reports also suggest that HPV infection could be a risk factor for esophageal cancer. However, most of the previous studies on HPV involvement in esophageal carcinomas have included only small numbers of biopsy specimens, thus necessitating additional studies based on extensive series of esophageal samples. METHODS: A series of 776 biopsy specimens derived from 363 patients who had undergone esophagectomy for squamous cell carcinoma in the high-incidence area of China were analyzed for the presence of HPV DNA by screening and specific typing in situ hybridization with biotinylated HPV DNA probes. RESULTS: Under low-stringency conditions, 85 (23.4%) tumors were demonstrated to contain HPV DNA: Positive signals were found on the nuclei of cancer cells in 71 (19.6%), in the surrounding epithelial cells with hyperplastic or dysplastic changes in 13 (3.6%), in the cancer cells and the surrounding epithelial cells in 10 (2.8%), and in the resected margins in 1 (0.3%). Thirty-four (40%) of the 85 HPV-positive tumors were shown to contain at least one type of HPV 6, 11, 16, 18, or 30 DNA sequences. HPV 16 was the type found most frequently, occurring in 18.8% of the 85 HPV-positive specimens. In addition to the primary tumors, HPV DNA sequences were found in 12.3% (7 of 57) of the lymph node metastases. CONCLUSION: The results confirm the previously reported HPV involvement in esophageal squamous cell lesions and implicate HPV as a potential etiologic agent in the multifactorial pathogenesis of esophageal carcinoma.

Adult↗
PubMed1993

Covalently bound lipids in keratinizing epithelia.

Covalently bound lipids have been identified and compared in keratinizing porcine epithelia including epidermis and oral epithelium from palate and gingiva. Stratum corneum was isolated by tryptic digestion, and after extensive extraction of lipids using a series of chloroform-methanol mixtures, the residual tissue was subjected to alkaline hydrolysis to release covalently bound lipids. The lipids so released were analyzed by quantitative thin-layer chromatography. Stratum corneum from each of the three anatomical sites contained omega-hydroxyceramides, omega-hydroxyacids and fatty acids. In epidermal stratum corneum the total covalently bound lipids represented 2.4% of the dry weight of the tissue, but in the oral epithelia this figure was consistently lower: 0.24% in palatal stratum corneum and 0.20% in gingival stratum corneum. Transmission electron microscopy before and after lipid extraction confirms the presence of a lipid envelope in epidermal stratum corneum and demonstrates the absence of this structure in oral stratum corneum.

Animals↗
PubMed1993

Phosphatase inhibition by calyculin A increases i(f) in canine Purkinje fibers and myocytes.

The actions of the phosphatase inhibitor calyculin A on the pacemaker current i(f) were studied in canine Purkinje fibers and myocytes. Calyculin A increased i(f) in response to hyperpolarizations toward the middle of the i(f) activation curve. A three pulse protocol indicated this increase was due to a positive shift of i(f) activation on the voltage axis. Taken together with our previous results (that kinase inhibition with H7 shifts i(f) activation in the negative direction on the voltage axis (2)), these results suggest that phosphorylation is an important regulator of the voltage dependence of i(f) activation.

Animals↗
PubMed1993

Localization of beta-glucosidase activity within keratinizing epithelia.

1. Serial frozen sections (10 microns thick) were cut parallel to the plane of the epithelium from skin, hard palate and gingiva of the pig (Sus scrofa), and beta-glucosidase activity was measured in each section. 2. In each of these tissues, there was a low constitutive level of beta-glucosidase activity in the inner portion of the epithelium, and a several-fold increase in activity was observed in the region of the stratum granulosum-stratum corneum interface. 3. The maximum specific activity of beta-glucosidase was significantly lower in gingiva (8 nmol substrate/hr/slice) than in epidermis and palate (15-18 nmol/hr/slice). 4. The increase in expression of beta-glucosidase activity near the stratum granulosum-stratum corneum boundary appears to be intimately involved in the conversion of glucosylceramides to ceramides in the final stages of differentiation. This conversion may be a major determinant of the barrier properties of the stratum corneum.

Animals↗
PubMed1993

Tumourigenesis associated with the p53 tumour suppressor gene.

The p53 gene is contained within 16-20 kb of cellular DNA located on the short arm of human chromosome 17 at position 17p13.1. This gene encodes a 393-amino-acid nuclear phosphoprotein involved in the regulation of cell proliferation. Current evidence suggests that loss of normal p53 function is associated with cell transformation in vitro and development of neoplasms in vivo. More than 50% of human malignancies of epithelial, mesenchymal, haematopoietic, lymphoid, and central nervous system origin analysed thus far, were shown to contain an altered p53 gene. The oncoproteins derived from several tumour viruses, including the SV40 large T antigen, the adenovirus E1B protein and papillomavirus E6 protein, as well as specific cellular gene products, e.g. murine double minute-2 (MDM2), were found to bind to the wild-type p53 protein and presumably lead to inactivation of this gene product. Therefore, the inactivation of p53 tumour suppressor gene is currently regarded as an almost universal step in the development of human cancers. The current data on p53-associated tumourigenesis are briefly discussed in this minireview.

Amino Acid Sequence↗
PubMed1993

Negative regulation of FAR1 at the Start of the yeast cell cycle.

In budding yeast, a switch between the mutually exclusive pathways of cell cycle progression and conjugation is controlled at Start in late G1 phase. Mating pheromones promote conjugation by arresting cells in G1 phase before Start. Pheromone-induced cell cycle arrest requires a functional FAR1 gene. We have found that FAR1 transcription and protein accumulation are regulated independently during the cell cycle. FAR1 RNA and protein are highly expressed in early G1, but decline sharply at Start. Far1 is phosphorylated just before it disappears at Start, suggesting that modification may target Far1 for degradation. Although FAR1 mRNA levels rise again during late S or G2 phase, reaccumulation of Far1 protein to functional levels is restricted until after nuclear division.

Base Sequence↗
PubMed1993

Pacemaker current exists in ventricular myocytes.

I(f), the "cardiac pacemaker current," is a nonselective cation channel activated on hyperpolarization in primary and secondary pacemaker regions of the mammalian heart. The cardiac pacing rate can be modulated by shifting the activation of I(f) to more positive (faster pacing) or more negative (slower pacing) voltages. We report for the first time the presence of this pacemaker current in ventricular myocytes. The potential importance of this observation to the mechanism of differentiation of nonpacing regions in the heart is discussed.

Animals↗
PubMed1993

The p53 tumor suppressor gene as a common cellular target in human carcinogenesis.

The p53 gene is a 16-20 kb of cellular DNA located on the short arm of human chromosome 17 at position 17p13.1. This gene encodes a 375-amino acid nuclear phosphoprotein which involves in the regulation of cell proliferation. The p53 gene was originally regarded as a dominant oncogene because its overexpression resulted in the immortalization of rodent cells, and the p53 gene could transform rat embryonic fibroblasts in concert with an activated ras gene. It soon became clear, however, that many of the p53 clones that had been studied were in fact mutated versions of the gene, and the wild-type p53 actually acts as a tumor suppressor. Loss of normal p53 function has been associated with the cell transformation in vitro and the development of neoplasms in vivo. More than one-half of human malignancies derived from the epithelial, mesenchymal, hematopoietic, and lymphoid tissues, as well as the central nervous system, analyzed thus far, were shown to contain an altered p53 gene. Most p53 gene alterations are the missense mutations, giving rise to an altered protein. These mutations are most frequently located in the evolutionally conserved areas. Furthermore, it has been demonstrated that the SV40 large T antigen, the adenovirus E1B protein, and papillomavirus E6 protein can bind to wild-type p53 protein and presumably lead to inactivation of this gene product as well. Therefore, the inactivation of normal (or wild-type) p53 is currently regarded as an important genetic pathway for human carcinogenesis generated by endogenous factors and exogenous carcinogens, as well as several tumor viruses. The current data on the p53 gene and its alterations in human malignancies, particularly those in the gastrointestinal tract, are reviewed.

Amino Acid Sequence↗
PubMed1992

Mechanism of acetylcholine action on pacemaker current (i(f)) in canine Purkinje fibers.

We have recently reported in canine Purkinje fibers that acetylcholine (ACh) can reverse the positive voltage shift of the pacemaker current (i(f)) induced by beta-adrenergic stimulation while having no direct action of its own. We have now investigated this effect of ACh on the cyclic adenosine monophosphate (cAMP) cascade in more detail. We find that addition of a membrane permeable analogue of cAMP (8-chlorophenylthio cAMP), 0.5-1 mM, increased the amplitude of i(f). This action was not reversed by 1 microM ACh, implying that ACh acts at a step prior to cAMP action. We then looked at the steps controlling intracellular concentration of cAMP. Inhibiting the phosphodiesterase with 100 microM isobutyl-1-methylxanthine (IBMX) increased i(f). This action, however, was reversed by ACh. Finally we investigated whether the action of forskolin, a direct activator of adenylyl cyclase, could be reversed by ACh. Forskolin (10-20 microM) increased i(f), and ACh at 1 microM partially reversed this action of forskolin. These results suggest that, in canine Purkinje fibers, ACh reverses the positive action of beta-adrenergic agents on i(f) via a decrease in cAMP production.

Acetylcholine↗
PubMed1992

Infectious agents in the etiology of esophageal cancer.

Extensive epidemiological and experimental studies have suggested that some chemical agents, nutritional deficiencies, and physical factors are associated with the development of esophageal cancer (EC). Recent evidence also suggests an etiologic role of certain microorganisms in esophageal carcinogenesis either by producing carcinogens or promotors or by acting directly on the host cells. The mutagenic and carcinogenic effects of several fungi and bacteria isolated from the grains and foodstuffs in high-risk areas have been shown by in vitro and in vivo studies. Certain viruses, e.g., human papillomavirus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus, have been implicated in the pathogenesis of a variety of human cancers, and all of them are known to produce tumors in animals and cell transformation in vitro. These viruses also have been shown to infect the esophageal epithelium. Therefore, although many of the key issues of their mechanisms of action are unclear as yet, they should be considered potential etiologic agents of EC. The present review summarizes the data available on the etiology of EC, emphasizing the current evidence implicating an etiologic role of microorganisms in the pathogenesis of this malignancy.

Animals↗
PubMed1992

Study of elasto-gel pads used as surface bolus material in high energy photon and electron therapy.

Bolus materials are occasionally used during the high energy photon and electron radiation treatments of head, neck, breast, and chest wall areas in order to deliver the full prescribed dose to the skin surface and underlining tissue. Where skin surface curvatures make uniform contact between the bolus material and skin surface difficult, we have studied a new bolus material called Elasto-gel. Elasto-gel, packed in a sterilized envelope, is routinely used in the treatment of superficial burns and wounds. The adhesive nature of Elasto-gel bolus material provides excellent skin contact without air gaps. The Elasto-gel is made of non-toxic material and is transparent. High dose irradiation has no effect on the appearance and property of the Elasto-gel pad. We are presenting in this note the radiation attenuation and build up effects of the Elasto-gel pads of photon energies of 6 and 18 MV and of electron energies of 6 MeV and 20 MeV. There is little difference between Elasto-gel and Polystyrene in radiation dosimetry.

Electrons↗
PubMed1992

Prognostic factors in invasive cervical carcinomas associated with human papillomavirus (HPV). Quantitative data and cytokeratin expression.

As a part of a larger programme to search for the prognostic factors in cervical cancer, quantitative morphometry, demonstration of AgNORs and expression of different cytokeratin polypeptides (SK2-27, SK1, A 53-B/A2) were used to study a series of 85 cervical squamous cell carcinomas, previously analysed for the presence of human papillomavirus (HPV) DNA by in situ hybridization and polymerase chain reaction (PCR). The following nuclear profile parameters were calculated: nuclear area, perimeter, maximum diameter, ellipsoidity (form Ell), regularity (form Ar) and roundness (form Pe). In each case, the number of small (< 3 microns), large (> 3 microns), the total number and the ratio large/small AgNORs were registered. The cancer cell density and the lymphoid cell density were assessed. In the survival analysis, neither the expression of different cytokeratin polypeptides or the pattern of cytokeratin staining proved to be an independent variable. Similarly, none of the nuclear profile parameters analysed possessed an independent prognostic value in the survival analysis. The ratio of large/small AgNORs proved to be a significant independent prognostic predictor (p = 0.0104), second only to the lymphoid cell density. Also the total number of AgNORs was a prognostic indicator. This suggests that AgNOR size and ratio reflect tumor proliferation also in cervical squamous cell carcinoma, as shown in other human malignancies. Similarly, the density of cancer cell nuclei proved to be an independent prognostic predictor (p = 0.0601) in that the tumours in patients with longer survival showed lower density of the nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Phosphorylation of FAR1 in response to alpha-factor: a possible requirement for cell-cycle arrest.

Exposure of yeast a cells to alpha-factor causes cells to arrest in the G1 phase of the cell cycle. The FAR1 gene is required for this cell-cycle arrest; its product is necessary for the inhibition of a G1 cyclin, CLN2. Earlier work demonstrated that alpha-factor caused an increase in the transcription of FAR1 severalfold over a measurable basal level. We now show that transcriptional induction of FAR1 from a heterologous promoter is not sufficient to inhibit CLN2 in the absence of alpha-factor. We also show that FAR1 is phosphorylated in response to alpha-factor and propose that this phosphorylation may be required for FAR1 activity.

Base Sequence↗
PubMed1992

Investigation on the carcinogenic effects of coal tar pitch in rat respiratory tract by intratracheal instillations.

The effects of coal tar pitch (CTP) on the tracheobronchial mucosa of Wistar rats were studied. Three groups of animals received 10 weekly intratracheal instillations of CTP at the cumulative doses of 6.48, 136.56 and 200 mg respectively. The control group of rats received 10 weekly intratracheal instillations of charcoal powder at a cumulative dose of 20 mg. The study in which the animals were killed serially revealed that CTP had conspicuous damage on the respiratory system of rats, especially on the bronchiolo-alveolar areas. The lesions induced by CTP ranged from hyperplastic, metaplastic and dysplastic changes to extensive cancers. These lesions were usually multifocal, and were more severe in the rats receiving higher dosages of CTP. The deposition of CTP particles within or adjacent to these lesions could be readily identified. Lung cancers occurred in 12.5% (4/32) and 25% (10/40) of the rats treated with 136.56 and 200 mg of CTP, whereas no tumors were found in control rats and the rats that received 6.48 mg of CTP. The overall cancer incidence significantly related to the cumulative dose of CTP. The histological types of lung cancers consisted of squamous cell carcinomas (10 out of the 14 lung cancers), adenocarcinoma (1/14), and combined squamous and adenocarcinomas (3/14). The development of CTP-induced rat lung cancers appears to derive from the hyperplasias of bronchiolo-alveolar epithelium, and processing stages of squamous metaplasias and/or dysplasias to carcinomas. The present results confirmed the carcinogenic effects of CTP on the respiratory system of rats, and provided experimental evidence for human lung carcinogenesis, particularly in those occupationally exposed to coal tars or tar products.

Adenocarcinoma↗
PubMed1992

Southern blot hybridization and PCR in detection of oral human papillomavirus (HPV) infections in women with genital HPV infections.

The presence of human papillomavirus (HPV) in biopsies taken from clinically normal buccal mucosa (n = 212) and clinical lesions (n = 60) was examined by Southern blot hybridization (SBH) using 32P-labelled HPV DNA probes. Furthermore, one hundred formalin-fixed, paraffin-embedded biopsies were analyzed by using polymerase chain reaction (PCR), combined with dot blot hybridization and biotinylated HPV DNA probes. With SBH and PCR, 15.4% and 29.4% of the biopsies, respectively, contained HPV DNA. In clinically normal epithelium, 15.6% and 23.1% of the samples were HPV-positive with SBH and PCR, respectively. The HPV types detected in the genital and oral mucosa of index patients differed in all except two cases. Histology could not be relied on distinguishing HPV DNA positive and HPV DNA negative samples. Hand warts were encountered significantly more frequently in patients with a concomitant oral HPV infection. To conclude, oral HPV infections as detected by SBH and PCR are surprisingly common, but similar to the genital tract, the virus seems to exist in a latent form in the vast majority of cases. The frequent concomitant finding of skin warts and oral HPV infection may suggest some kind of HPV-specific immunosuppression.

Alcohol Drinking↗