Biomedical subjects

N H Park

Publications and source records attributed to N H Park.

At least 19 recordsLinked to original sources

PubMed1995

Divergent selection for blood serum insulin-like growth factor I concentration in beef cattle: I. Nongenetic effects.

Data were obtained from an ongoing experiment involving divergent selection for blood serum IGF-I concentration in purebred Angus cattle. The experiment includes approximately 100 spring-calving (50 high and 50 low line) and 100 fall-calving (50 high and 50 low line) cows. The selection criterion is the mean of IGF-I concentrations measured on each animal at d 28, 42, and 56 of the postweaning performance test. Mean IGF-I values were available for a total of 526 bull and heifer calves. Pooled across years and breeding seasons, high line progeny averaged 21 +/- 6, 17 +/- 6, and 23 +/- 5 ng/mL more IGF-I (P < .01) than low line progeny at d 28, 42, and 56 of the postweaning test. Season effects on IGF-I approached statistical significance only at d 42 and 56 of the postweaning period. Pooled across years and selection lines, spring minus fall differences were 9 +/- 10 (P = .52), -17 +/- 10 (P = .10), -22 +/- 9 (P = .07), and -9 +/- 6 (P = .45) ng/mL for IGF-I concentrations at d 28, 42, and 56 of the postweaning test and for mean IGF-I, respectively. Sex effects on serum IGF-I concentration were highly significant, with greater IGF-I expression in bulls, but were confounded with diet and location. Age of dam effects were not significant. Regressions of IGF-I concentration on on-test age of calf ranged from .46 +/- .13 to 1.08 +/- .20 ng.mL-1.d-1 and were highly significant for all measures of IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1992

Effect of ibuprofen on the in vitro and in vivo reactivation of latent HSV-1.

Prostaglandins have been suggested to play an important role in the reactivation of latent herpes simplex virus. To further understand the role of prostaglandins in the reactivation process, we investigated the effects of ibuprofen, a nonsteroidal anti-inflammatory drug with prostaglandin synthesis inhibitory activity, on the in vitro and in vivo reactivation of latent type 1 herpes simplex virus in mouse ganglia and rabbits, respectively. Ibuprofen, at a concentration of 50 or 100 microM, did not alter the titer of reactivated virus from explanted ganglia with latent virus, but, at a concentration of 200 or 500 microM, it significantly reduced the reactivated viral titer from the ganglia. Ibuprofen also directly inhibited the replication of herpes simplex virus in trigeminal ganglia and Vero cell monolayers, which indicates that the drug reduced the recovery of reactivated viral titers from explanted ganglia with latent virus by acting on the replication process rather than on the reactivation mechanism in vitro. The systemic administration of ibuprofen failed to demonstrate any significant effect on the ocular shedding of virus after attempted reactivation by 6-hydroxydopamine iontophoresis in rabbits with latent herpes simplex virus infection. This failure in vivo could be due to the short half-life and low concentration of ibuprofen at the site of reactivation and replication of latent virus. Alternatively, in the clinical setting, it is conceivable that ibuprofen may not have an effect on in vivo reactivation of latent herpes.

Animals↗

PubMed1992

Low p53 level in immortal, non-tumorigenic oral keratinocytes harboring HPV-16 DNA.

The p53 protein level was determined in normal oral keratinocytes and two non-tumorigenic, immortal oral keratinocyte lines harboring human papillomavirus-16 (HPV-16)DNA. The p53 mRNA level in the immortal cells was higher than the normal counterpart, but the p53 protein level was notably lower in the immortalised cells. The half-life of p53 protein in the normal and immortal cells was < 1 h, and the p53 cDNA sequence of these cells showed no mutation. The immortal cells transcribed a high amount of E6/E7 mRNA encoded by HPV-16, but normal cells did not. These observations suggest that the immortal keratinocytes may translate normal level of wild-type p53 protein, and the low p53 level in these cells may be due to the enhanced degradation of the protein by HPV-16 E6 protein.

Blotting, Northern↗

PubMed1992

In vitro and animal studies of the role of viruses in oral carcinogenesis.

The linkage of herpes simplex virus (HSV) and human papillomavirus (HPV) to the development of oral cancer has been studied. In spite of the presence of viral nucleic acids in some human oral cancer specimens, HSV alone is not carcinogenic in animals: repeated viral inoculation to mouse or hamster oral mucosa fails to produce tumours or histopathological evidence of malignancy. However, HSV demonstrates co-carcinogenicity in vivo: viral inoculation significantly enhances the oncogenic capacity of chemical carcinogens in the oral cavity of mice and hamsters. Though the detailed mechanisms of HSV cocarcinogenicity are unknown, HSV promotes the chemical carcinogen-induced activation of certain cellular proto-oncogenes and inactivation of p53 tumour suppressor gene. Human papillomaviruses type 16 (HPV-16) and 18 (HPV-18) demonstrate oncogenicity by transforming normal human oral keratinocytes in vitro. While normal cells exhibit a limited life-span, cells transformed by these viruses show immortality and altered morphology in comparison with their normal counterparts. The HPV-immortalised cells contain multiple copies of intact viral genome integrated into cellular chromosomes. These cells also express several viral-specific mRNAs including viral E6/E7 mRNAs. Notably, these cells contain low levels of p53 protein and overexpressed cellular myc proto-oncogene compared to their normal counterpart; however, the immortilised cell lines are non-tumorigenic in nude mice.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1992

Sequential combined tumorigenic effect of HPV-16 and chemical carcinogens.

We immortalized oral keratinocytes by transfection with recombinant human papillomavirus type 16 (HPV-16) DNA and established two cell lines, human oral keratinocytes-16A (HOK-16A) and -16B (HOK-16B). These cell lines were morphologically different from the normal counterpart, contained HPV-16 DNA as integrated form and expressed numerous viral genes. However, these cells proliferated only in culture medium containing low calcium (0.15 mM) and are not tumorigenic in nude mice. To test the hypothesis that tumors can be developed by sequential combined effect of human papillomavirus and chemical carcinogens in the oral cavity, these immortalized cell lines were chemically transformed by exposure to either benzo[a]pyrene or methanesulfonic acid ethyl ester. Such transformants proliferated in medium containing physiological calcium levels (1.5 mM) and demonstrated enhanced growth potential in nude mice, whereas primary human oral keratinocytes treated with these chemical carcinogens failed to show any evidence of transformation. Chemically transformed cells contained integrated, intact HPV-16 sequences and transcribed significantly higher amount of HPV-16 E6/E7 messages and transforming growth factor-alpha (TGF-alpha) compared with the immortalized oral keratinocytes. Like the HPV-immortalized cell lines, the chemically transformed oral keratinocytes contained lower levels of newly synthesized, wild-type p53 proteins compared to normal cells, and expressed wild-type c-Ha-ras. These results indicate that this in vitro system is useful for investigating the mechanisms of multistep oral carcinogenesis.

Base Sequence↗

PubMed1991

Effect of Herpes simplex virus infection on the trigeminal jaw-opening reflex in guinea pigs.

Herpes simplex virus (HSV) infection induces numerous electrophysiological and microscopic changes in neurons in vitro. To investigate the effect of HSV infection on in vivo neuronal activity, we induced an acute, latent and reactivated HSV infection of the trigeminal ganglia of guinea pigs through orofacial HSV inoculation and studied its effect on the trigeminal jaw-opening reflex of anesthetized guinea pigs. During the acute viral infection period both the threshold for elicitation of the reflex, and the latency to the onset of the reflex response were increased. During the latent viral infection in the trigeminal ganglia, the jaw-opening reflexes in the viral infected animals were not different from those of non-infected control animals. However, reactivation of the latent viral infection in these animals resulted in increases in both the threshold and latency of the jaw-opening reflex. These changes were similar to those found in animals with the acute viral infection. These results indicate that acute or reactivated latent HSV infection of the nervous system results in functional changes in the reflex pathways involving the trigeminal gasserian ganglia and brainstem neurons harboring infectious HSV-1.

Animals↗

PubMed1991

Three cell lines from hamster buccal pouch tumors induced by topical 7,12-dimethylbenz(a)anthracene, alone or in conjunction with herpes simplex virus inoculation.

Three squamous carcinoma cell lines HBPC-1, HBPC-2, and HBPC-3 were established from hamster buccal pouch tumors induced by topical 7,12-dimethylbenz(a)anthracene (DMBA) treatment alone, topical DMBA treatment in conjunction with type 1 herpes simplex virus (HSV-1) inoculation, and topical DMBA application in combination with type 2 HSV (HSV-2) inoculation, respectively. The cells were epithelial in morphology, had a doubling time of approximately 18 h, and required bovine serum for optimal growth. They demonstrated an in vitro anchorage-independent growth and produced squamous cell carcinomas when transplanted into normal hamster pouch submucosa. The carcinoma cell lines equally expressed cellular hst, src, abl, and raf proto-oncogenes that were not expressed in the normal hamster pouch epithelial cells. An equal amount of fos gene expression was noticed in the normal pouch epithelial cells, HBPC-1 and HBPC-3, but the HBPC-2 expressed less fos poly(A+)RNA than the other cell lines. The myc proto-oncogene was also expressed both in the normal pouch epithelial cells and in the cancer cell lines. However, the size and number of expressed myc poly(A+)RNA in the normal cells and cancer cell lines differed. Although the normal cells and HBPC-1 expressed a single myc transcript, 1.7-kilobase (kb) and 2.3-kb, respectively, both HBPC-2 and HBPC-3 expressed two myc poly(A+)RNAs, 1.7-kb and 2.3-kb.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Anchorage-independent growth and the expression of cellular proto-oncogenes in normal human epidermal keratinocytes and in human squamous cell carcinoma cell lines.

The expression of multiple cellular proto-oncogenes and the in vitro anchorage-independent growth of normal human epidermal keratinocytes and several human squamous cell carcinoma cell lines were studied and correlated. Squamous cell carcinoma cell lines KB, Si Ha, HEp-2, and Fa Du showed high anchorage independency, and MS 751 and A-253 cell lines had minimum independency. However, the normal keratinocytes and the A-431 cell line did not show anchorage-independent growth. Both the normal human epidermal keratinocytes and cancer cell lines expressed multiple proto-oncogenes such as src, erb B-1, abl, fos, raf, H-ras, and myc, and the amount of expression of these oncogenes was notably higher in the cancer cell lines than in the normal keratinocytes. The expression of proto-oncogenes from the monolayer cultures of the cancer cell lines is poorly correlated with the anchorage independency of the cells. These data indicate that the anchorage independency is not directly linked to the expression of specific cellular proto-oncogene(s) of the monolayer cancer cell cultures.

Autoradiography↗

PubMed1991

Effect of smokeless tobacco and tobacco-related chemical carcinogens on survival of ultraviolet light-inactivated herpes simplex virus.

Low doses of ultraviolet (UV) light, x-rays, photodynamic treatment, or aflatoxins increase the survival of UV-irradiated virus in cells. This effect is postulated to occur by enhancement of the error-prone cellular repair function, which could also be associated with oncogenic cell transformation. The present study was designed to investigate whether treatment of green monkey kidney cells with water extract of snuff (snuff extract), benzo[a]pyrene, nicotine, or tobacco-specific N'-nitrosamines would result in enhanced survival of UV-irradiated herpes simplex virus (HSV). Exposure of the cells with snuff extract, benzo[a]pyrene. N'-nitrosonornicotine, or 4-(N-methyl-N'-nitrosamino)-1-(3-pyridyl)-1-butanone resulted in an enhancement of survival of UV-irradiated HSV type 1 compared with the control whereas exposure of the cells with nicotine did not. These data indicate that the water-extractable component of snuff and tobacco-related chemical carcinogens increase the cellular repair mechanism and provides for increased survival of UV-irradiated HSV.

Animals↗

PubMed1991

Combined synergistic antiherpetic effect of acyclovir and chlorhexidine in vitro.

The combined effect of acyclovir and chlorhexidine on the replication and DNA synthesis of herpes simplex virus was studied. Acyclovir and chlorhexidine showed synergism in the inhibition of the viral replication by enhancing in part the reduction of viral DNA synthesis. These data indicate that combined therapy with acyclovir and chlorhexidine might be beneficial for the control of intraoral herpetic infections.

Acyclovir↗

PubMed1991

Synergism of herpes simplex virus and tobacco-specific N'-nitrosamines in cell transformation.

Previous studies indicate that herpes simplex virus (HSV) enhances the carcinogenic activity of smokeless tobacco and tobacco-related chemical carcinogens in animals. Since tobacco-specific N'-nitrosamines (TSNAs) such as N'-nitrosonornicotine (NNN) and 4-(N-methyl-N'-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are major chemical carcinogens of smokeless tobacco and are known to be responsible for the development of oral cancers in smokeless tobacco users, the combined effects of TSNAs and HSV in cell transformation were investigated. Exposure of cells to NNN or NNK followed by virus infection resulted in a significant enhancement of transformation frequency when compared with that observed with chemical carcinogens or virus alone. This study suggests that TSNAs and HSV can interact together and show synergism in cell transformation.

Animals↗

PubMed1991

Immortalization of normal human oral keratinocytes with type 16 human papillomavirus.

Primary human oral keratinocytes were transformed by transfection with recombinant human papillomavirus type 16 (HPV-16) DNA, and two transformed cell lines named human oral keratinocytes-16A and -16B (HOK-16A and HOK-16B) were established. While normal cells and cells transfected with vector only exhibited a limited lifespan, the HOK-16A and HOK-16B lines demonstrated immortality and altered morphology from their normal counterpart. The HOK-16A and HOK-16B lines contained approximately 40 and approximately 25 copies of intact HPV-16 DNA as integrated form per cell respectively, and both cell lines expressed several viral specific poly(A+) RNAs. Notably these cell lines also overexpressed cellular myc proto-oncogene in comparison with the normal counterpart. However, the immortalized cell lines were not able to produce tumors in nude mice, indicating that the cells are partially transformed. The HOK-16A and HOK-16B lines are, therefore, useful for investigating the multistep molecular events of oral carcinogenesis.

Blotting, Northern↗

PubMed1990

Active HSV-1 immunization prevents the cocarcinogenic activity of HSV-1 in the oral cavity of hamsters.

Previous investigations have demonstrated that herpes simplex virus (HSV) increased the oral carcinogenic activity of 7,12-dimethylbenz[a]anthracene (DMBA) probably by enhancing the DMBA-induced amplification and overexpression of c-erb-B-1 proto-oncogene in hamster buccal pouch epithelium. The present study investigated the effect of active type 1 HSV (HSV-1) immunization on the development of oral cancer induced by HSV-1 and DMBA, alone or in combination, in the hamster buccal pouch. The results were similar to our previous report in that HSV-1 significantly enhanced the oncogenic effect of DMBA, and the numbers of pouches harboring tumor nodules and the numbers and sizes of tumors developed by topical DMBA were significantly increased by HSV-1 inoculation to the site of the DMBA application. Although HSV-1 immunization did not alter the carcinogenic activity of DMBA in animals receiving topical DMBA in combination with mock inoculation, it prevented the cocarcinogenic effect of HSV-1 in animals receiving topical DMBA in conjunction with HSV-1 inoculation. These data indicate that active HSV-1 immunization completely obstructs the co-oncogenic effect of HSV-1 in the oral cavity of hamsters.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1990

Effect of snuff extract on the replication and synthesis of viral DNA and proteins in cells infected with herpes simplex virus.

The water-extractable component of snuff (snuff extract) inhibits the replication of herpes simplex virus (HSV) by suppressing the synthesis of viral DNA. This process probably causes HSV to be oncogenic. To further understand the mechanism of inhibitory action of snuff extract on HSV replication, the effect of snuff extract on the synthesis of viral DNA and proteins in type 1 HSV (HSV-1) infected cells was investigated. Snuff extract inhibited the synthesis of viral DNA and altered the production of certain classes of viral proteins. The syntheses of ICP4, a viral alpha-protein, and ICP8, a beta-protein, were not generally reduced by noncytotoxic concentrations of snuff extract (where ICP = infected cell polypeptide). However, snuff extracts significantly inhibited the production of ICP gC (glycoprotein C), a gamma 2-protein, and the inhibition was in a concentration-dependent fashion: the higher the concentration of snuff extracts, the greater the inhibition. Based on the fact that the production of alpha- and beta-proteins is absolutely necessary for and precedes the viral DNA synthesis and that viral gamma 2-proteins are mostly produced by the newly synthesized viral DNA, it is concluded that snuff extract inhibits HSV-1 DNA replication directly rather than indirectly via the alteration of viral protein synthesis.

Cell Line↗

PubMed1989

The effects of benzo(a)pyrene, nicotine, and tobacco-specific N-nitrosamines on the generation of human lymphokine-activated killer cells.

The effects of four major components of snuff (fine-cut smokeless tobacco) on the development of lymphokine-activated killer cells (LAK) were measured in vitro. Of the components tested: nicotine, N'-nitrosonornicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo(a)pyrene (BaP), only BaP suppressed LAK cytotoxicity against tumour targets and LAK DNA synthesis during 3- and 7-day incubations. BaP concentrations of 0.1-1.0 micrograms/ml suppressed lymphocyte proliferation only; there was no effect on tumour cell proliferation at these concentrations. BaP had no effect on tumour target killing when incubated during 4 h natural killer (NK) or LAK cytotoxicity assays. There was no effect on LAK binding of tumour targets after 3 days culture with BaP concentration of 0.1-1.0 micrograms/ml. These data confirm that a water-soluble extract of snuff has anti-cytolytic and anti-proliferative effects on peripheral blood lymphocytes. As NK and LAK cells are important in preventing tumourigenesis and metastasis, suppression of these cells may favour neoplastic growth associated with snuff-dipping.

Benzopyrenes↗

PubMed1989

Herpes simplex virus enhances the 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis and amplification and overexpression of c-erb-B-1 proto-oncogene in hamster buccal pouch epithelium.

We studied the effects of herpes simplex virus type 1 (HSV-1) inoculation and topical 7,12-dimethylbenz[a]anthracene (DMBA) application, alone or in combination, on the carcinogenesis and on the amplification and expression of various cellular proto-oncogenes in hamster buccal pouch tissue. Topical DMBA treatment produced tumor formation in pouches, but HSV-1 inoculation, alone caused no neoplastic changes. In pouch tissues receiving both DMBA application and HSV-1 inoculation, the development of initial leukoplakia and tumor has hastened and enhanced in comparison with those receiving DMBA alone. Topical DMBA application to pouch tissue induced an amplification and an increase in the expression of cellular erb-B-1 (c-erb-B-1) proto-oncogene in the epithelial tissue, whereas repeated infection with HSV-1 alone did not. Topical DMBA combined with HSV-1 inoculation, however, resulted in greater amplification and expression of c-erb-B-1 proto-oncogene in the pouch epithelial tissue compared to the DMBA alone. These data indicate that HSV-1 inoculation significantly increases the carcinogenic activity of DMBA, in part, by probably enhancing DMBA-induced amplification and expression of c-erb-B-1 proto-oncogene in hamster buccal pouch tissue.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1989

Effect of smoked tobacco tar on the growth, cytolytic action, DNA synthesis, and gene expression of herpes simplex virus.

Previous experiments have shown that topical application of smoked tobacco tar condensate to HSV-infected oral mucosae of mice promotes neoplastic changes. Although HSV is an oncogenic virus, the virus must be inactivated and lose its cytolytic activity to be oncogenic in vitro and in vivo. Therefore, we investigated the effect of the water-extractable components of smoked tobacco tar condensate (smoked tobacco tar extract) on the growth, cytolytic activity, DNA synthesis, and gene expression of type 1 herpes simplex virus (HSV-1). Diluted tar extracts in tissue culture medium markedly inhibited the replication and cytolytic activity of HSV-1 in vitro. The smoked tobacco tar extract also notably inhibited the synthesis of viral DNA and late gene expression in a dose-dependent manner. The synthesis of alpha- and beta-classes of viral proteins was not affected by the extract. Therefore, it is probable that the smoked tobacco tar extract inhibits the synthesis of viral DNA directly rather than indirectly by depressing early gene expression.

Animals↗

PubMed1989

Effect of chlorhexidine on the in vitro and in vivo herpes simplex virus infection.

Several investigations have recently shown that chlorhexidine (CHX) has antiviral activity, and they have indicated possible clinical use of CHX for the control of intraoral herpes simplex virus (HSV) infection. In the present study, we have evaluated the in vitro and in vivo therapeutic efficacy of CHX against type 1 HSV (HSV-1) infection. CHX moderately, but significantly, inhibited the replication and cytolytic activity of HSV-1 in Vero cell monolayers. When 0.2% CHX was applied topically onto the HSV-1 infected forehead skin of mice, the development of viral lesions and the viral titers in the skin and trigeminal ganglia were also moderately reduced. These data indicate that CHX oral rinse may be beneficial for the control of intraoral HSV-1 infection in certain patients, and warrants further controlled clinical study.

Animals↗