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Biomedical subjects

F Chang

Publications and source records attributed to F Chang.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1992

Human papillomavirus involvement in esophageal precancerous lesions and squamous cell carcinomas as evidenced by microscopy and different DNA techniques.

A series of 71 surgically resected esophageal squamous cell carcinomas, including 51 cases of formalin-fixed samples and 20 cases of fresh biopsy specimens derived from the high-incidence area of esophageal cancer in China, were systematically analyzed for the presence of human papillomavirus (HPV) infections by light microscopy, electron microscopy (TEM), in situ DNA hybridization, Southern blot hybridization, and polymerase chain reaction (PCR) techniques. On light microscopy, HPV-suggestive lesions were found in a total of 49.0% (25 of 51) of the specimens, including the flat type (22 of 51) and, less frequently, an inverted one (2 of 51). Of the 51 formalin-fixed, paraffin-embedded specimens, 43.1% (22 of 51) contained HPV DNA sequences by in situ hybridization. Of the positive cases, HPV 6 was present in three (5.9%), HPV 11 in three (5.9%), HPV 16 in eight (15.7%), HPV 18 in six (11.8%), double infections with HPV 11/18 in one (2.0%), and HPV 16/18 in one. In most cases the HPV-positive signals were localized in the hyperplastic and/or dysplastic epithelium adjacent to invasive carcinomas. In two specimens, however, HPV DNA sequences were found in the frankly invasive lesions, one being HPV 6 and the other HPV 18. On TEM, HPV-like particles located in the nuclei of koilocytotic cells were demonstrated in two of the five specimens previously shown to be HPV-positive by in situ hybridization. By means of the PCR technique, all specimens positive for HPV by in situ hybridization also contained amplified HPV sequences. Moreover, three additional samples negative by in situ hybridization were found to contain HPV 11 DNA sequences. Of the 20 DNA samples extracted from the fresh carcinoma samples (containing some surrounding tissues as well) 9 were shown to contain HPV DNA sequences by Southern blot hybridization under low-stringency conditions. Of these, eight samples remained positive when hybridized with the probe cocktail of HPV 11, 16, 18, and 30 DNA under high-stringency conditions. HPV DNA sequences in these carcinoma specimens appeared to be present mainly in an integrated form. The present results confirm the HPV involvement in esophageal squamous cell lesions and suggest that HPV infection might be an important etiologic factor in the pathogenesis of esophageal cancer, most probably acting synergistically with other carcinogenic factors.

Blotting, Southern↗
PubMed1992

Natural history of cervical human papillomavirus lesions does not substantiate the biologic relevance of the Bethesda System.

The newly introduced Bethesda System proposes to replace the terms dysplasia, carcinoma in situ (CIS), or cervical intraepithelial neoplasia (CIN) with two terms, low-grade squamous intraepithelial lesion (SIL) or high-grade SIL. We tested the biologic relevance of the Bethesda System (ie, its ability to establish a close correlation between biologic behavior and the different grades of lesions) in a series of 528 women with genital human papillomavirus (HPV)-associated precancerous lesions prospectively followed for 10 years. The cervical biopsies were reclassified as either low-grade or high-grade SIL, and the data obtained by colposcopy, Papanicolaou smear, and HPV typing, as well as the biological behavior of the lesions, were analyzed in these two groups. Altogether, 77.4% (376 of 486) of the lesions were classified as low-grade SIL lesions; the rest (22.6%) belonged to the high-grade SIL category. In the low-grade SIL category, 46.8% of the women were 24 years old or younger, as compared with 37.3% in the high-grade SIL group. The colposcopic appearance was normal significantly more frequently in the low-grade SIL lesions (22.1%) than in the high-grade category (8.5%) (P less than .001). A single Papanicolaou smear was inadequate to distinguish between low-grade and high-grade SIL, as evidenced by almost identical distributions of Papanicolaou smear class I and II cells in both categories. Noteworthy was the discovery of normal Papanicolaou smears in 8.2% of the high-grade SIL lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Inhibition of glycogen synthesis in Saccharomyces cerevisiae by the mating pheromone alpha-factor.

Treatment of the yeast Saccharomyces cerevisiae with the pheromone alpha-factor caused an inhibition of glycogen synthesis in MATa haploid cells but not in MAT alpha cells or MATa/MAT alpha diploid cells. The concentration of alpha-factor required for a half-maximal inhibition was comparable to that required for the induction of the FUS1 gene. Strains containing a disruption in ste2 or ste12 or temperature-sensitive mutations in ste4, ste7, or ste11 continued to divide and to accumulate glycogen in the presence of alpha-factor. In contrast, inhibition of glycogen occurred upon exposure to mating pheromone of far1 mutants which, under this condition, fail to arrest in G1 and continue to divide while simultaneously undergoing the transcriptional induction and morphological changes typical of mating cells. The inhibition of glycogen accumulation by alpha-factor persisted in a strain lacking glycogen phosphorylase (EC 2.4.1.1), which ruled out the participation of this enzyme in the pheromone response. Glycogen synthase (EC 2.4.1.11) from a cells treated with alpha-factor was found primarily in the glucose 6-phosphate-dependent (inactive) form whereas the total activity was unaltered. This indicates that the action of mating pheromone is mainly to inhibit the interconversion of the inactive glucose 6-phosphate-dependent form to the active glucose 6-phosphate-independent form of glycogen synthase without affecting the concentration of the enzyme.

Amino Acid Sequence↗
PubMed1991

Block of the cardiac pacemaker current (If) in the rabbit sino-atrial node and in canine Purkinje fibres by 9-amino-1,2,3,4-tetrahydroacridine.

We have investigated the action of 9-amino-1, 2, 3, 4-tetrahydroacridine (THA) on the pacemaker current If in rabbit sino-atrial node myocytes and in canine Purkinje fibers. THA at concentrations in the range 3-300 microM blocked If in a voltage-independent manner, as revealed by measurements on the fully activated I/V relation for If. The dose/response relationship of the If maximal slope conductance (Gf) can be fitted by assuming a cooperative binding reaction where two THA molecules are required to block one If channel. Half-maximal block occurred at 18.2 microM in the sino-atrial node and 36.6 microM in Purkinje fibers. THA also affected the If kinetic properties. This was examined in the sino-atrial node where the current activation curve was shifted in the negative direction on the voltage axis (- 21 mV at 30 microM THA). The delayed rectifier current, IK, was also reduced by THA in sino-atrial node myocytes: at - 40 mV the IK fully activated value was decreased to 37% of its control value by 30 microM THA, with only a minor modification of the position of the activation curve at the same potential. Thus, although THA blocks If at a lower concentration than other known If-channel blockers [DiFrancesco (1982) J Physiol (Lond) 329:485-507], its action on the pacemaker current is not specific.

Animals↗
PubMed1991

Comparison of glycosidase activities in epidermis, palatal epithelium and buccal epithelium.

1. beta-Glucosidase, alpha-glucosidase, beta-galactosidase and alpha-mannosidase were measured in epidermis, palatal and buccal epithelium of the pig (Sus scrofa). 2. All three epithelia contained similar alpha-mannosidase activity (1.7-3.2 nmol mg tissue-1 hr-1 at pH 4), and none contained significant alpha-glucosidase. 3. Specific activity of beta-glucosidase was high (9-13 nmol mg tissue-1 hr-1 at pH 4) in epidermis and palate, but activity was low (less than 2 nmol mg tissue-1 hr-1) in buccal epithelium. 4. Only epidermis contained a high level of beta-galactosidase (5.8 nmol mg tissue-1 hr-1). 5. Differences in glycosidase profiles may underlie differences in permeability barrier properties in these epithelia.

Animals↗
PubMed1991

Human papillomavirus (HPV) infections and their associations with oral disease.

More than 65 distinct types of human papillomavirus (HPV) have been identified to date. Several of the HPV types have been proposed as etiologic agents of squamous cell carcinoma. In the oral cavity, HPVs have been found associated with several benign squamous cell proliferations. Evidence from histology and DNA hybridization studies suggests that HPV is also involved in oral carcinogenesis. It is apparent, however, that substantial amount of confusion exists in the diagnosis of oral HPV infections. The keratotic, papillary lesions in the oral cavity are usually small and easily overlooked. The gross appearance of these viral lesions is not distinct enough to be readily diagnosed by the clinicians. Degenerative changes found on oral mucosa frequently simulate koilocytosis. Thus, caution should be exercised to avoid overdiagnosis of HPV infection in the oral cavity. The present review summarizes the current evidence available on HPV infections in general and on oral HPV infections in particular. The diagnostic techniques available as well as the problems encountered in the distinction of these lesions are also discussed in short.

Humans↗
PubMed1991

Effects of protein kinase inhibitors on canine Purkinje fibre pacemaker depolarization and the pacemaker current i(f).

1. The effects of the protein kinase inhibitors H-7 and H-8 were investigated on diastolic depolarization of the action potential with microelectrodes and on the pacemaker current if with the two-microelectrode voltage clamp in canine cardiac Purkinje fibres. 2. Both 200 microM-H-7 and 100 microM-H-8 had no significant effect on the slope of diastolic depolarization but eliminated the actions of isoprenaline (1 microM). 3. We examined the actions of H-7 and H-8 on if in the presence and absence of isoprenaline. H-7 (200 microM) shifted the pacemaker current if in the negative direction on the voltage axis, whereas 100 microM-H-8 had no significant effect by itself. Both 200 microM-H-7 and 100 microM-H-8 can reverse or prevent the actions of isoprenaline (1-5 microM) on if. 4. We applied activators of the cyclic AMP cascade down-stream to the beta-receptor, to further evaluate where H-7 and H-8 might be exerting their effects. When exposing Purkinje fibres to an adenylyl cyclase activator (forskolin, 10-50 microM), a phosphodiesterase inhibitor (IBMX, 100 microM) and a permeable cyclic AMP analogue (8-chlorophenylthio-cyclic AMP, 200 microM-1 mM), the amplitude of if was increased. H-7 and H-8 at 100-200 microM eliminated each of these actions. 5. These results suggest that a phosphorylation process is involved in the modulation of the pacemaker current, if, in Purkinje fibres. The different actions of H-7 and H-8 on basal if suggest the hypothesis that other protein kinases, possibly protein kinase C, might also be involved in regulating basal phosphorylation of if in Purkinje fibres.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Esophageal squamous cell papillomas. Failure to detect human papillomavirus DNA by in situ hybridization and polymerase chain reaction.

Squamous cell papilloma of the esophagus has been regarded as a distinct rarity. After having reviewed the files of the Gastrointestinal Endoscopy Unit of our hospital we found 14 patients diagnosed as having an esophageal papilloma on endoscopy of about 18,000 patients during the period 1985-90. On histologic examination of the biopsy specimens 12 cases showed histologic characteristics typical of a squamous cell papilloma (SQP), 1 was a fibroid polyp, and another showed epithelial dysplasia without the features typical of SQP. To assess the role of human papillomavirus (HPV) recently implicated in the etiology of this tumor, we analyzed all specimens for the presence of HPV types 6, 11, 16, and 18 DNA by in situ DNA hybridization (ISH) and polymerase chain reaction (PCR). No viral DNA was found by either ISH or PCR in any of these lesions. The significance of these findings is discussed in relation to the previous evidence presented on HPV involvement in the development of esophageal squamous cell papillomas and in esophageal carcinogenesis.

Adult↗
PubMed1990

Identification of a gene necessary for cell cycle arrest by a negative growth factor of yeast: FAR1 is an inhibitor of a G1 cyclin, CLN2.

alpha factor is a negative growth factor and differentiation factor that induces G1 arrest and increases transcription of mating genes in S. cerevisiae a cells. We have identified a gene, FAR1 (for "factor arrest"), which is necessary for cell cycle arrest but not for other responses to alpha factor: far1- mutants are insensitive to arrest despite having an intact signal transduction pathway. FAR1 is a nonessential gene whose expression is induced 4- to 5-fold in a cells by alpha factor. The sequence of FAR1 indicates no significant similarities to known proteins. A null mutation in the CLN2 gene, which codes for a G1 cyclin, reverses the effect of a far1 null mutation: far1- cln2- strains arrest in response to alpha factor. We thus propose that FAR1 contributes to cell cycle arrest by inhibiting CLN2. The behavior of far1- cln2- strains indicates that products other than FAR1 are responsible for inhibiting the other G1 cyclins, CLN1 and CLN3.

Amino Acid Sequence↗
PubMed1990

Human papillomavirus (HPV) DNA in esophageal precancer lesions and squamous cell carcinomas from China.

A series of 51 biopsies derived from the same number of patients with established invasive squamous-cell carcinoma of the esophagus in Linxian, a high-risk area for esophageal cancer in China, were analyzed histologically and by in situ DNA hybridization to demonstrate human papillomavirus (HPV) infection. Epithelial changes suggesting HPV infection within or adjacent to the carcinoma lesions were found in 25 cases (49.0%). Esophageal lesions with HPV morphology showed both flat (25 cases) and inverted condylomas (2 cases) resembling those found in the genital tract. HPV 6, 11, 16 or 18 DNA sequences were detected in 22/51 (43.1%) of the esophageal specimens. HPV DNA was most frequently localized in epithelium adjacent to carcinomas in areas showing either epithelial hyperplasia (36.1%) or dysplasia (22.2%). Of the lesions with morphological HPV changes, 64% (16/22) were shown to contain HPV DNA. In 2 specimens, HPV DNA was found in frankly malignant cells. High-risk types HPV 16 and/or 18 DNA sequences were found in 16 of the 22 HPV DNA-positive cases (72.7%). Our results confirm previously reported HPV involvement in esophageal squamous-cell lesions, and support the hypothesis of HPV as a possible etiological agent in esophageal carcinogenesis.

Adolescent↗
PubMed1990

Detection of human papillomavirus (HPV) DNA in oral squamous cell carcinomas by in situ hybridization and polymerase chain reaction.

A series of 156 formalin-fixed, paraffin-embedded biopsies from 40 patients with surgically-treated oral squamous cell carcinomas was analysed for the presence of human papillomavirus (HPV) infection by histopathological evaluation, in situ DNA hybridization and polymerase chain reaction (PCR). Epithelial changes suggesting a HPV lesion within, or adjacent to, the carcinoma lesions were found in 16 out of 40 patients (40%). Morphological signs of a flat HPV lesion were found in four cases (10%), those of inverted type in three cases (7.5%), and those of papillary type in nine cases (22.5%). HPV DNA was demonstrated in one of the lesions by in situ hybridization with biotin-labelled DNA cocktail probe containing HPV types 6, 11, 16 and 18. With the PCR technique, samples from 11 (27.5%) of the 40 patients proved to contain HPV DNA. Of these, HPV 6 was demonstrated in one case, HPV 16 in ten cases and HPV 18 in one case. HPV DNA was exclusively detected in the biopsies showing carcinoma tissue or its adjacent precancer lesions. No viral DNA was found in the biopsies derived from the tumour-free resection margins. These results provide further evidence to support the concept of HPV involvement in the aetiology of oral squamous cell carcinomas, most probably acting synergistically with other carcinogens.

Base Sequence↗
PubMed1990

CDC36 and CDC39 are negative elements in the signal transduction pathway of yeast.

Mutations in either the CDC36 or CDC39 gene cause yeast cells to arrest in G1 of the cell cycle at the same point as treatment with mating pheromone. We demonstrate here that strains harboring temperature-sensitive mutations in CDC36 or CDC39 activate expression of the pheromone-inducible gene FUS1 when shifted to nonpermissive temperature. We show further that cell-cycle arrest and induction of FUS1 are dependent on known components of the mating factor response pathway, the STE genes. Thus, the G1-arrest phenotype of cdc36 and cdc39 mutants results from activation of the mating factor response pathway. The CDC36 and CDC39 gene products behave formally as negative elements in the response pathway: they are required to block response in the absence of pheromone. Epistasis analysis of mutants defective in CDC36 or CDC39 and different STE genes demonstrates that activation requires the response pathway G protein and suggests that CDC36 and CDC39 products may control synthesis or function of the G alpha subunit.

G1 Phase↗
PubMed1990

Detection of human papillomavirus (HPV) in genital warts and carcinomas by DNA in situ hybridization in Chinese patients.

A series of 51 genital biopsies from normal epithelium, condylomata acuminata, leucoplakia and squamous cell carcinoma from Chinese male and female patients were analysed for the presence of human papillomavirus (HPV) types 6, 11, 16 and 18 by DNA in situ hybridization. All of the nine genital condyloma acuminata were positive for HPV DNA, in which HPV 6 was found in six cases, HPV 11 in two cases and HPV 18 in one case. Twelve out of the 21 cases (57.1% of the total) of cervical squamous cell carcinoma were shown to contain HPV DNA; HPV 16 was found in nine cases, HPV 18 in two cases and HPV 16/18 in one case. Present results support the earlier concept that HPV 6/11 are closely associated with benign genital lesions, and HPV 16/18 are mostly confined to higher grade of intra-epithelial neoplasias and carcinoma.

Adult↗
PubMed1990

Verrucous carcinoma of the anus containing human papillomavirus type 16 DNA detected by in situ hybridisation: a case report.

Verrucous carcinoma of the anus is a distinct and rare variant of well-differentiated squamous cell carcinoma. A case of anal verrucous carcinoma in a 35 year old man was studied by light microscopy and in situ DNA hybridization. Human papillomavirus (HPV) type 16 DNA sequences were demonstrated in the tumour cells, as well as in cells showing koilocytotic and dyskeratotic changes. The possible viral (HPV) aetiology of verrucous carcinoma is considered with a review of the previous literature.

Adult↗
PubMed1990

Acetylcholine reverses effects of beta-agonists on pacemaker current in canine cardiac Purkinje fibers but has no direct action. A difference between primary and secondary pacemakers.

We have investigated the actions of acetylcholine in the absence and presence of the beta-agonist isoproterenol in cardiac Purkinje fibers. beta-Agonists, like isoproterenol, increase the magnitude of the pacemaker current (If) in cardiac myocytes by shifting its activation voltage more positive on the voltage axis. We find that acetylcholine has no effect on If in the absence of isoproterenol. However, if If is first increased by beta-agonist stimulation, acetylcholine can then return If to control levels. This effect on If is exerted through muscarinic receptors since atropine prevents this action of acetylcholine. Functionally, this action of acetylcholine can guarantee the maintenance of ventricular pacemakers when there is high parasympathetic tone but can also prevent extra ventricular beats when sympathetic and parasympathetic tone are both high.

Acetylcholine↗