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Biomedical subjects

T F Tsai

Publications and source records attributed to T F Tsai.

At least 19 recordsLinked to original sources

Role of breast tumour kinase in the in vitro differentiation of HaCaT cells.

BACKGROUND: Breast tumour kinase (BRK) is a newly identified non-receptor protein tyrosine kinase from a metastatic breast tumour. Its biological functions are still under extensive investigation. The mouse homologue Sik (Src-related intestinal kinase) has been implicated in mouse keratinocyte differentiation; however, not much is known about the functions of BRK in human cutaneous biology. OBJECTIVES: Using HaCaT cells as an experimental model, to explore the mutual relationships between BRK and differentiation of human keratinocytes. METHODS: Archival paraffin blocks of normal and pathological skin were retrieved for examining the in vivo distribution of BRK. Its expression and subcellular localization were examined via indirect immunofluorescence, and quantitative changes were analysed by Northern and Western blots. The kinase activity of BRK was determined by its autophosphorylation and phosphorylation of exogenous substrate in the in vitro kinase assay. Using a retroviral infection method, we established stably transfected HaCaT cells expressing vector, wild-type BRK or a kinase-defective mutant (K219M). Expression of the differentiation marker keratin 10 (K10) was compared among these cells using semiquantitative reverse transcription-polymerase chain reaction. Results Histochemical examination showed that BRK was expressed exclusively in suprabasal keratinocytes. Its distribution was both cytoplasmic and intranuclear. An enhanced regional suprabasal expression pattern was observed in the confluent areas of cell cultures. The expression of BRK transcript and protein was up-regulated in prolonged confluence culture in a serum-dependent manner. Its kinase activity was activated shortly after the addition of calcium and ionomycin and returned to the basal level within 30 min. Overexpression of wild-type BRK moderately promoted the expression of K10 transcript while the kinase-defective BRK mutant exerted a prominent suppressive effect. CONCLUSIONS: The in vivo distribution of BRK and its up-regulation during in vitro differentiation of HaCaT cells, together with the activation of its kinase activity by calcium/ionomycin and its influence on K10 expression, all indicate a role for BRK in the complex process of keratinocyte differentiation.

Blotting, Western↗

Clinical value of early cleavage embryo.

OBJECTIVE: This study was undertaken to see if embryo transfer containing early cleavage embryos resulted in better clinical pregnancy rate. METHODS: The treatment outcomes of IVF-ET were retrospectively reviewed. Out of 258 transfer cycles, 160 cycles contained no early cleavage embryos (Group I) and 98 cycles contained at least one early cleavage embryo (Group II). The definition of early cleavage embryo is the presence of two blastomeres 24-26 h after insemination. The implantation rate, clinical pregnancy rate were compared between two groups. Student's t-test and the Mann-Whitney U-test were used for continuous variables, and the Chi-squared (chi(2)) test was used for binary variables. Differences were considered statistically significant at P<0.05. RESULT: The implantation rate and clinical pregnancy rate were 11.6% and 25.6% in Group I, 18.6% and 38.8% in Group II (P<0.05). CONCLUSION: Early cleavage embryos possess greater implantation potential. Embryo transfer containing early cleavage embryos had a better clinical pregnancy rate.

Adult↗

The phosphotidyl inositol 3-kinase/Akt signal pathway is involved in interleukin-6-mediated Mcl-1 upregulation and anti-apoptosis activity in basal cell carcinoma cells.

Dysregulation of interleukin-6 has been reported to be associated with various types of tumors, and interleukin-6 plays an important part in regulating apoptosis in many types of cells. Previously, Mcl-1 was shown to be significantly increased in interleukin-6-overexpressed basal cell carcinoma cells and conferred on them anti-apoptotic activity. The aim of this study was to investigate which signaling pathway is involved in the anti-apoptotic effect of interleukin-6 on basal cell carcinoma cells. Here we show that the addition of recombinant 100 ng per ml interleukin-6 to basal cell carcinoma cells induced a 2.3-fold increase in the level of Mcl-1 protein in basal cell carcinoma cells. Transfection with dominant-negative STAT3 (STAT3F) into inter-leukin-6-treated basal cell carcinoma cells caused a decrease of phosphotyrosyl STAT3 but did not alter Mcl-1 protein levels; however, AG490, a Janus tyrosine kinase inhibitor, was capable of inhibiting the interleukin-6-induced elevation of Mcl-1 protein. Next, interleukin-6 stimulation elicited extracellular signal-regulated kinase activation in basal cell carcinoma cells, and the mitogen-activated protein kinase inhibitor, PD98059, could affect this response without affecting the interleukin-6-medi-ated Mcl-1 upregulation. Use of the two phosphotidyl inositol 3-kinase inhibitors, LY294002 and wortmannin, to check whether this pathway is involved in Mcl-1 upregulation by interleukin-6, we found that the phosphotidyl inositol 3-kinase inhibitors completely attenuated the interleukin-6-induced Mcl-1 upregulation. Furthermore, in the interleukin-6-overexpressing basal cell carcinoma cell clone, dominant-negative Akt also significantly reduced the increased level of Mcl-1. Interestingly, Janus tyrosine kinase inhibitor, AG490, treatment strongly blocked the phosphotidyl inositol 3-kinase pathway activation, as evidenced by the decrease in phospho-Akt level. Blockage of phosphotidyl inositol 3-kinase/Akt pathway abolished the interleukin-6-mediated anti-apoptotic activity in ultraviolet B treated cells. Unexpectedly, without ultraviolet B irradiation, STAT3F transfection also induced a significant apoptosis in basal cell carcinoma/interleukin-6 cells. Taken together, our data suggest that both the phosphotidyl inositol 3-kinase/Akt and STAT3 pathways are potentially involved in interleukin-6-mediated cell survival activity in basal cell carcinoma cells; however, the upregulation of the anti-apoptotic Mcl-1 protein by interleukin-6 is mainly through the Janus tyrosine kinase/phosphotidyl inositol 3-kinase/Akt, but not the STAT3 pathway.

Apoptosis↗

Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases.

BACKGROUND: In 1998, the US Centers for Disease Control and Prevention was notified of three patients who developed severe illnesses days after yellow fever vaccination. A similar case occurred in 1996. All four patients were more than 63 years old. METHODS: Vaccine strains of yellow fever virus, isolated from the plasma of two patients and the cerebrospinal fluid of one, were characterised by genomic sequencing. Clinical samples were subjected to neutralisation assays, and an immunohistochemical analysis was done on one sample of liver obtained at biopsy. FINDINGS: The clinical presentations were characterised by fever, myalgia, headache, and confusion, followed by severe multisystemic illnesses. Three patients died. Vaccine-related variants of yellow fever virus were found in plasma and cerebrospinal fluid of one vaccinee. The convalescent serum samples of two vaccinees showed antibody responses of at least 1:10240. Immunohistochemical assay of liver tissue showed yellow fever antigen in the Kuppfer cells of the liver sample. INTERPRETATION: The clinical features, their temporal association with vaccination, recovery of vaccine-related virus, antibody responses, and immunohistochemical assay collectively suggest a possible causal relation between the illnesses and yellow fever vaccination. Yellow fever remains an important cause of illness and death in South America and Africa; hence, vaccination should be maintained until the frequency of these events is quantified.

Adverse Drug Reaction Reporting Systems↗

The SNRPN promoter is not required for genomic imprinting of the Prader-Willi/Angelman domain in mice.

In mice and humans, the locus encoding the gene for small nuclear ribonucleoprotein N (SNRPN/Snrpn), as well as other loci in the region are subject to genomic imprinting. The SNRPN promoter is embedded in a maternally methylated CpG island, is expressed only from the paternal chromosome and lies within an imprinting center that is required for switching to and/or maintenance of the paternal epigenotype. We show here that a 0.9-kb deletion of exon 1 of mouse Snrpn did not disrupt imprinting or elicit any obvious phenotype, although it did allow the detection of previously unknown upstream exons. In contrast, a larger, overlapping 4.8-kb deletion caused a partial or mosaic imprinting defect and perinatal lethality when paternally inherited.

Angelman Syndrome↗

Adverse events after Japanese encephalitis vaccination: review of post-marketing surveillance data from Japan and the United States. The VAERS Working Group.

We determined the reporting rates for adverse events following the administration of inactivated mouse-brain derived Japanese encephalitis vaccine (JEV) based on post-marketing surveillance data from Japan and the United States. The rate of total adverse events per 100,000 doses was 2.8 in Japan and 15.0 in the United States. In Japan, 17 neurological disorders were reported from April 1996 to October 1998 for a rate of 0.2 per 100,000 doses. In the United States, no serious neurological adverse events temporally associated with JEV were reported from January 1993 to June 1999. Rates for systemic hypersensitivity reactions were 0.8 and 6.3 per 100,000 doses in Japan and the United States, respectively. Passively collected VAERS surveillance data indicate that characteristic hypersensitivity reactions with a delayed onset continue to occur among JEV recipients and that conservative recommendations limiting its use to travelers at high risk of infection with Japanese encephalitis are appropriate.

Adolescent↗

New initiatives for the control of Japanese encephalitis by vaccination: minutes of a WHO/CVI meeting, Bangkok, Thailand, 13-15 October 1998.

Japanese encephalitis (JE) is a leading cause of viral encephalitis in Asia that, in several countries, has been controlled effectively through national vaccine programs. However, in recent years, transmission has been recognized or has intensified in new locations where the available vaccines are either unaffordable or unlicensed. In addition, the near-eradication of poliomyelitis from Asia has elevated JE in the public health agenda of preventable childhood diseases, and surveillance of acute neurological infections to confirm polio eradication, simultaneously, has led to a greater awareness of the disease burden attributable to JE. The only internationally licensed JE vaccine, an inactivated mouse-brain derived vaccine, is efficacious but is problematic from the perspectives of reactogenicity, requirement for numerous doses, cost and reliance on a neurological tissue substrate. A live-attenuated vaccine distributed only in China also is efficacious and requires fewer doses; however, production and regulatory standards are unresolved. Several approaches toward developing novel JE vaccines that could fill the gap in JE vaccine need are under pursuit. The minutes and recommendations of a meeting of experts to discuss these issues, jointly sponsored by the World Health Organization and the Children's Vaccine Initiative in Bangkok, Thailand, 13-15 October, 1998, are presented.

Animals↗

Hantavirus infection in Taiwan: the experience of a geographically unique area.

Hantaviruses are rodent-borne viruses, and they, mainly the Hantaan (HTN) serotype, are the causative agents of a group of febrile nephropathies known as "hemorrhagic fever with renal syndrome (HFRS). " Despite the fact that HFRS is frequently reported in China, with an annual incidence of 50,000-100,000 cases, one puzzling observation that no local case of HFRS has been confirmed in Taiwan has yet to be explained. We hypothesized that the hantavirus strain prevailing in Taiwan mainly belongs to the mild strain, the Seoul (SEO) strain, and the absence of severe disease was related to the absence of HTN. To test these hypotheses, this epidemiologic study was performed, including a seroprevalence survey and phylogenetic analysis on hantavirus isolated from the rodent population trapped in major seaports, rural, and mountainous areas of Taiwan. This study also included rodents and viruses from two isolated islands, Kinmen and Matzu, which are geographically adjacent to the east coast of mainland China. There were a total of 5,461 rodents of 16 species captured, and R. norvegicus was the most common species, with an antibody prevalence much higher in international seaports (20%) than in rural regions (approximately 5%) and intermediate in some domestic seaports. By reverse transcriptase polymerase chain reaction (RT-PCR), 33.9% of the seropositive R. norvegicus were found to have amplifiable hantavirus sequences in their lung tissues, and subsequent phylogenetic analyses indicated that almost all hantavirus in Taiwan was most closely related to the prototype SEO strain, and no HTN strain was recovered from any rodent species indigenous to Taiwan. The seroprevalence of SEO infection in R. norvegicus on Kinmen and Matzu was also different from that in southern provinces of China but closely resembled that in seaports in Taiwan, and the SEO identified was genetically linked to Taiwanese SEO strains. These results substantiate our hypotheses, and suggest that the epidemiology of hantavirus infection in Taiwan are different from that in China, where the HTN and SEO strains and HFRS concurrently prevail.

Animals↗

Epidemiological features of and public health response to a St. Louis encephalitis epidemic in Florida, 1990-1.

A St. Louis encephalitis (SLE) epidemic in Florida during 25 weeks in 1990-1, resulted in 222 laboratory-diagnosed cases, an attack rate in the 28 affected counties of 2.25/100,000. Disease risk rose with advanced age, to 17.14/100,000 in persons over 80 years, and all 14 fatal cases were in persons over 55 years (median, 70 years). Community serosurveys in Indian River County, the epicenter of the outbreak (attack rate 21/100,000), showed acute asymptomatic infections in 3.6% of the persons surveyed, with higher rates in persons with outdoor occupational exposure (7.4%) and in clients of a shelter for the indigent (13.3%). A matched case-control study found that evening outdoor exposure for more than 2 h was associated with an increased risk for acquiring illness (odds ratio [OR] 4.33, 95% CI 1.23-15.21) while a number of recommended personal protective measures were protective. Four SLE patients were dually infected with Highlands J virus, the first reported cases of acute infection with this alphavirus. The case-control study provided the first evidence that a public education campaign to reduce exposure had a protective effect against acquiring the disease.

Adolescent↗

Effects of glycolic acid on light-induced skin pigmentation in Asian and caucasian subjects.

BACKGROUND: Topical use of alpha-hydroxy acid (AHA) may increase skin photosensitivity, as demonstrated by increased numbers of sunburst cells. However, effects of AHA on tanning have not been studied. OBJECTIVE: Our purpose was to study whether short-term use of glycolic acid hastens resolution of pre-existing light-induced pigmentation and whether the skin becomes tan more easily in Asian and Caucasian subjects after such treatment. METHODS: Six Asian and six Caucasian volunteers received separate irradiations of UVB and UVA to both sides of the lower back. In a double-blind fashion, patients then applied a 10% glycolic acid gel, pH 3.52, to one side of the back, including the irradiated area, and the contralateral extensor forearms once daily for 7 days and then twice daily for 2 weeks. A placebo gel, pH 5.75, was applied to the opposite sides. The subjects returned for measurement of residual tanning with a colorimeter and received additional irradiation to forearms and a second site on the back. Resulting pigmentation was measured immediately after irradiation, at 2 hours, and at 1 week. RESULTS: Increased UVB-induced skin tanning occurred on the forearm and the lower back in both races in areas pretreated with glycolic acid. UVA also caused increased tanning, but only on the extensor forearms in Asian subjects. Treatment with glycolic acid for 3 weeks had no effect on pre-existing light-induced pigmentation. CONCLUSION: Short-term topical treatment of glycolic acid caused an increase in UVB tanning as well as in UVA tanning in some subjects, even in the absence of overt irritation. The inclusion of UVB, and even UVA, sunscreen in AHA products may be warranted.

Adult↗

Continued transmission of West Nile virus to humans in southeastern Romania, 1997-1998.

After an epidemic of West Nile (WN) virus neurologic infections in southeastern Romania in 1996, human and animal surveillance were established to monitor continued transmission of the virus. During 1997 and 1998, neurologic infections were diagnosed serologically as WN encephalitis in 12 of 322 patients in 19 southeastern districts and in 1 of 75 Bucharest patients. In addition, amid a countrywide epidemic of measles, the etiology of the febrile exanthem in 2 of 180 investigated cases was determined serologically to be WN fever; 1 case was complicated by hepatitis. Sentinel chickens placed in Bucharest seroconverted to WN virus during the summer months, indicating their potential value in monitoring transmission. The continued occurrence of sporadic WN infections in southeastern Romania in consecutive years after the 1996 epidemic is consistent with local enzootic transmission of the virus.

Adolescent↗

Evaluation of immunoglobulin M (IgM) and IgG enzyme immunoassays in serologic diagnosis of West Nile Virus infection.

A unique urban encephalitis epidemic in Romania signaled the emergence of neurological infection due to West Nile (WN) virus as a novel public health threat in Eastern Europe and provided an opportunity to evaluate patterns of immunoglobulin G (IgG) and IgM reactivity in IgM capture and IgG enzyme-linked immunosorbent assays (ELISAs). WN virus infection was diagnosed serologically in 236 of 290 patients from whom acute serum or cerebrospinal fluid (CSF) samples were available. In 37% of serum samples and in 25% of CSF samples collected in the first week of illness, anti-WN virus IgM antibody was detected in the absence of virus-specific IgG. The switch to an IgG antibody response occurred after 4 to 5 days of illness and earlier in CSF than in serum. A specific humoral immune response was detected in the CSF before the serum in some patients for whom paired CSF and serum samples from the same day were available. IgM antibody in convalescent serum samples persisted beyond 2 months after the onset of illness in more than 50% of patients. ELISA optical density values and antibody concentrations were well correlated for both IgM and IgG immunoassays. Anti-WN virus IgM antibody in acute-phase samples did not cross-react significantly with flaviviruses in other antigenic groups.

Antibodies, Viral↗

Primary and booster immune responses to SA14-14-2 Japanese encephalitis vaccine in Korean infants.

Attenuated SA14-14-2 Japanese encephalitis (JE) vaccine has been administered safely and effectively to more than 100 million children in China since 1988 and recently, licensure of the vaccine in Korea has been sought. In the first clinical evaluation of the vaccine outside of China, we monitored side effects in 84 children and evaluated antibody responses to a single dose given as primary JE vaccination in 68 children, 1-3 years old (mean age 27 months). No significant adverse events were noted. Neutralizing antibodies (geometric mean titer [GMT] of 188) were produced in 96% of the 68 subjects. In 10 other children who previously had been immunized with two or three doses of inactivated JE vaccine, the booster administration of SA14-14-2 vaccine produced an anamnestic response in all, with a GMT of 3378. In a comparison group of 25 children previously immunized with two doses of inactivated vaccine, neutralizing antibody titers were detected in 16 (64%). Viral specific IgM was detected in nine primary vaccinees (13%) but in others, IgM may have declined to undetectable levels in the four week postimmunization sample. Live attenuated SA14-14-2 JE vaccine is a promising alternative to the only commercially available JE vaccine for national childhood immunization programs in Asia.

Antibodies, Viral↗

Evidence that mutational activation of the ras genes may not be involved in aflatoxin B(1)-induced human hepatocarcinogenesis, based on sequence analysis of the ras and p53 genes.

Exposure to aflatoxin B(1) (AFB(1)) is one of the risk factors for developing hepatoma. In rats, activation of the ras gene is a prevalent event in AFB(1)-induced hepatocarcinogenesis. It is not clear whether a similar event occurs in humans. By analysis of codon 249 of the p53 gene, six of 36 human hepatoma samples were found to show a G-->T transversion, suggesting that AFB(1) may be a risk factor for hepatocarcinogenesis. However, analysis at codons 12, 13, and 61 in the ras family genes revealed a A-->T transversion at codon 61 of the N-ras gene in a single tumor. Apparently, ras activation is rare in human hepatoma, and the mutation detected might not be induced by AFB(1). This suggests that activation of the ras gene may not be a major event in AFB(1)-related human hepatocarcinogenesis.

Aflatoxin B1↗

Anaphylaxis from yellow fever vaccine.

BACKGROUND: There are very few reports of anaphylactic reactions to yellow fever (YF) vaccine in the literature, and these date from the 1940s. OBJECTIVE: We sought to estimate the rate of YF vaccine-related anaphylaxis. METHODS: All reports of adverse reactions to YF vaccine submitted to the Vaccine Adverse Event Reporting System between 1990 and 1997 were reviewed for those meeting criteria for probable or possible anaphylactic reactions. RESULTS: Of 243 reports submitted, 40 describe probable or possible anaphylactic reactions. In 22 of these 40, YF vaccine was the only vaccine administered. There were 5,236,820 doses of YF vaccine distributed in the United States during this period. By using all 40 cases, the rate of YF vaccine-related anaphylaxis would be 40 in 5, 236,820 or about 1 in 131,000. In 35 of the reports, information was provided on whether previous doses of YF vaccine had been given. In 34 of these 35, the reaction occurred after the first dose of YF vaccine, suggesting that vaccine constituents other than the viral proteins may have been the allergens. The vaccine is grown in chicken embryos and contains gelatin as a stabilizer. CONCLUSION: YF vaccine can cause anaphylactic reactions. Persons presenting for YF vaccine should be asked if they have had adverse reactions to previous doses of this or other vaccines and if they are allergic to eggs, chicken, or gelatin. Health care workers administering YF vaccine should be prepared to recognize and treat anaphylactic reactions should they occur.

Adverse Drug Reaction Reporting Systems↗

Contact leukomelanosis induced by the leaves of Piper betle L. (Piperaceae): a clinical and histopathologic survey.

BACKGROUND: In April 1997, an unusual pigmentary disorder was noticed by dermatologists in Taiwan. All patients had a history of using facial dressings with steamed leaves of Piper betle L. (Piperaceae). OBJECTIVE: Our purpose was to clarify the evolution and the origin of this unique leukomelanosis. METHODS: Fifteen patients with an unusual pigmentary disorder, who visited our clinic in September and October 1997, were asked to complete a questionnaire designed to elicit the history related to the disorder. Eight of these 15 patients underwent skin biopsies: 6 on the mottled hyperpigmented area (group A) and 2 on the hypopigmented area (group B). All 8 specimens were prepared with hematoxylin-eosin, Masson-Fontana, and S-100 stains. RESULTS: The results of the questionnaire revealed that these patients had all experienced a temporary erythematous reaction in the first few days of the use of the facial dressing, and 9 of them also complained of an accompanying stinging sensation. A bleaching effect became noticeable approximately 1 week to 1 month later. Eight patients reported that the hyperpigmentation and confetti-like hypopigmentation occurred after overexposure to the sun. In both groups, histopathologic examination revealed some melanophages in the dermis. Masson-Fontana staining of specimens from group A showed local interspersed depigmentation and hyperpigmentation in the basal epidermis and pigmentary incontinence in the dermis. This picture was different from the homogeneous depigmentation within basal epidermis in specimens from group B. In both groups, S-100 staining was negative for melanocytes in the depigmented area. CONCLUSION: The clinical course and histopathologic findings suggest that the evolution of this pigmentary disorder can be divided into 3 stages. The first stage is the immediate bleaching stage, when an irritant reaction is usually conspicuous. The second stage consists of prominent hyperpigmentation visible both grossly and microscopically. The final stage is characterized by confetti-like depigmentation. It may be induced by chemicals in the betel leaves such as phenol, catechol, and benzene derivatives, perhaps through inhibition of melanin synthesis or melanocytotoxicity.

Adult↗