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S L Yang

Publications and source records attributed to S L Yang.

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

Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.

Two lines of transgenic (Tg) mice expressing high (H) levels of the mutant P101L prion protein (PrP) developed a neurologic illness and central nervous system pathology indistinguishable from experimental murine scrapie; these mice were designated Tg(MoPrP-P101L)H. Brain homogenates from Tg(MoPrP-P101L)H mice were inoculated intracerebrally into CD-1 Swiss mice, Syrian hamsters, and Tg196 mice, Tg mice expressing the MoPrP-P101L transgene at low levels. None of the CD-1 mice developed central nervous system dysfunction, whereas approximately 10% of hamsters and approximately 40% of the Tg196 mice manifested neurologic signs between 117 and 639 days after inoculation. Serial transmission of neurodegeneration in Tg196 mice and Syrian hamsters was initiated with brain extracts, producing incubation times of approximately 400 and approximately 75 days, respectively. Although the Tg(MoPrP-P101L)H mice appear to accumulate only low levels of infections prions in their brains, the serial transmission of disease to inoculated recipients argues that prion formation occurs de novo in the brains of these uninoculated animals. These Tg mouse studies, taken together with similar findings in humans dying of inherited prion diseases, provide additional evidence that prions lack a foreign nucleic acid.

Animals↗
PubMed1994

Prion isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and transgenic mice.

Different prion isolates, often referred to as "strains," present an enigma because considerable evidence argues that prions are devoid of nucleic acid. To investigate prion diversity, we inoculated three "strains" of prions into congenic and transgenic mice harboring variable numbers of two different alleles, designated a and b, of the prion protein (PrP) structural gene, Prn-p. The length of the incubation time was inversely related to the number of Prn-p(a) genes in mice inoculated with the Rocky Mountain Laboratory (RML) prion strain. Results with mice lacking this locus (Prn-p0/0) and transgenic mice argue that long incubation times are not a dominant trait as thought for many years, but rather they are due to reduced levels of the substrate PrPC-A (cellular isoform of PrP, allotype A) in (Prn-p(a) x Prn-pb)F1 mice. In contrast, the Prn-p(a) gene extended incubation times in mice inoculated with the 87V and 22A prion strains, whereas the Prn-pb gene was permissive. Experiments with the 87V isolate suggest that a genetic locus distinct from Prn-p controls deposition of the scrapie isoform of PrP (PrPSc) and attendant neuropathology. Each prion isolate produced distinguishable patterns of PrPSc accumulation in brain; of note, the patterns in Prn-p(a) and Prn-pb congenic mice inoculated with RML prions were more different than those in congenic Prn-pb mice with RML or 22A prions. Our results suggest that scrapie "strain-specific" incubation times can be explained by differences in the relative efficiency of allotypic interactions that lead to conversion of PrPC into PrPSc.

Alleles↗
PubMed1994

The neuropathological phenotype in transgenic mice expressing different prion protein constructs.

Neuropathologic examination of transgenic (Tg) mice which express different prion protein (PrP) constructs is essential because spongiform (vacuolar) degeneration of neurons, the distribution of PrPSc and whether PrP amyloid plaques form are the phenotypes of prion diseases. In Tg models of experimental scrapie, it was found that all of the parameters that define prion isolates ('strains') can be manipulated by changing the structure of PrP. In those studies, further evidence that PrPSc causes scrapie neuropathology and determines scrapie incubation time was obtained. In addition, the distribution of PrPSc in the brain was unique for each prion isolate. The implications of these findings are first, that prion isolates target different neuron populations for synthesis of nascent pathogenic PrPSc and, secondly, that prion isolate diversity is determined by neurons. In Tg mice which express mutated PrP mimicking human prion protein gene mutations linked to familial prion diseases, the neuropathological changes have been faithfully reproduced. A new age-related, neuromuscular disorder has also been identified in uninfected Tg mice which overexpress wild-type PrPc. All of the findings with different PrP constructs plus the absence of scrapie pathology in PrP null mice are the strongest argument that the prion protein is the main etiologic and pathogenic factor of prion disorders.

Age Factors↗
PubMed1994

Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins.

Prion diseases of humans and animals are known to be caused by infection with prions containing PrPSc or mutation of the prion protein (PrP) gene. During transgenetic studies, we discovered that uninoculated older mice harboring high copy numbers of wild-type (wt) PrP transgenes derived from Syrian hamsters (SHa), sheep (She), and PrP-B mice developed truncal ataxia, hindlimb paralysis, and tremors. These transgenic (Tg) mice exhibited a profound necrotizing myopathy involving skeletal muscle, a demyelinating polyneuropathy, and focal vacuolation of the central nervous system. Development of disease was dependent on transgene dosage. For example, half of all Tg(SHaPrP+/+)7 mice homozygous for the SHaPrP transgene array developed disease by approximately 460 days of age, while no hemizygous Tg(SHaPrP+/o)7 mice became ill before 650 days. The novel neurologic syndrome found in older Tg(wtPrP) mice implies that overexpression of wtPrPC is pathogenic and widens the spectrum of prion diseases.

Animals↗
PubMed1994

Cervical cytomegalovirus infection in prostitutes and in women attending a sexually transmitted disease clinic.

This study aimed to determine the frequency of, and to define factors associated with, cervical shedding of cytomegalovirus (CMV) in highly sexually active women (licensed prostitutes) and in women attending a sexually transmitted disease (STD) clinic. Cervical specimens obtained from 195 licensed prostitutes and 187 STD patients aged 17-50 years were compared for the presence of cervical CMV with specimens from 70 women of the same ages attending a gynecologic clinic. Cervical CMV was identified by the presence of a CMV-specific immediate-early gene sequence amplified by the polymerase chain reaction. Cervical CMV prevalences of 38.9% and 34.8% were found for licensed prostitutes and STD patients, respectively. These rates were significantly higher than the 24.3% cervical CMV prevalence for women attending the gynecologic clinic. The data suggest that frequent sexual contact with many sexual partners is responsible for the high frequency of cervical CMV observed in licensed prostitutes. The interaction between CMV and urogenital bacterial infections is a plausible explanation for the high cervical CMV prevalence in STD patients.

Adolescent↗
PubMed1994

Humoral immune responses and cytomegalovirus excretion in children with asymptomatic infection.

Forty-two seropositive children aged 3 to 5 years attending a kindergarten were followed up for 1 year in order to examine the relationship between humoral immunity and cytomegalovirus (CMV) excretion status. Anti-CMV antibodies were measured at the beginning and end of the study by enzyme-linked immunosorbent assay, neutralizing antibody test, and immunoblot techniques. Among these children, 32 persistently shed virus in urine, 2 intermittently shed CMV, and 4 experienced reactivation during the study. Virus was never isolated from 4 seropositive children. The level of anti-CMV IgG antibody in seropositive children who remained nonshedders was significantly higher than in children who shed virus during follow-up. On immunoblots, all seropositive nonshedders reacted to a CMV-specific 65 kD antigen, whereas most shedders (80%) did not. These findings suggest that humoral immunity plays a role in controlling persistent CMV infection in children with asymptomatic infection. However, the humoral immunity measured by the neutralizing test and the presence of antibodies against CMV-specific envelope antigens (116 kD/55 kD) apparently play a limited role in modifying persistent excretion and regulating reactivation of latent CMV. Immune evasion by CMV to block these antigens may explain these results.

Antibodies, Viral↗
PubMed1994

The effect of hyperthermic treatment on electroencephalographic recovery after interruption of respiration in rats.

Electroencephalography (EEG) was utilized for investigating the effect of hyperthermia followed by apneic hypoxia in rats. They were heated whole-bodily to 41 degrees C for 15 min under the control of an artificial rodent ventilator, after drug-induced generalized paralysis. A transcutaneous oxygen saturation monitor was applied to detect the hypoxic condition. EEG was monitored with bipolar needle electrodes. The 72-kDa heat-shock protein (HSP72) in brain was analyzed by sodium dodecyl sulfate-polyacrylamide electrophoresis, followed by immunostaining with an anti-HSP72 antibody. There was no difference in the time interval from onset of apneic hypoxia to flat EEG between the hyperthermic and control groups, but cortical electrical activity appeared earlier in the hyperthermia group than the control group, after 90 s of ventilation interruption. The cardiac function did not change in the two groups. The HSP72 synthesis significantly increased in the brain of the rats with hyperthermic treatment.

Animals↗
PubMed1994

Detection of dystrophin gene deletion in Chinese Duchenne/Becker muscular dystrophy patients utilizing multiplex polymerase chain reaction.

Multiplex PCR was utilized to detect deletions at the hot spot regions of dystrophin gene. Thirty-four cases of DMD and 7 cases of BMD, based on their clinical manifestations, were examined. Eight normal male adults were included as control. Eleven DNA fragments coding the exons 1, 3, 6, 8, 13, 17, 43, 47, 50, 52 and 60 were chosen and primers were prepared with oligonucleotide synthesizer. Multiplex PCR was performed under the condition of 94 degrees C 1 minute for denaturation, 65 degrees C 3 minutes for annealing, 72 degrees C 3 minutes for extension. Thirty cycles were followed by a last cycle with 7 minutes extension. Clinically, there were no significant differences between Chinese patients and those reported in other areas except the low rate of positive family history (32%). The results from multiplex PCR showed that 15 cases (37%), 11 DMD and 4 BMD, proved to have deletions in the exons studied; 1 located at exons 6 and 8, 1 at exon 8, 1 at exons 8, 13 and 17, 1 at exons 13 and 17, 1 at exon 17, 3 at exon 43, 1 at exon 50, and 3 at exons 50 and 52, after false negatives were excluded. No difference in size or location was noticed between DMD and BMD in the sample-limited result.

Adult↗
PubMed1993

Ablation of the prion protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies.

Mice, homozygous for prion protein (PrP) gene ablation (Prn-p0/0), develop normally and remain well > 500 days after inoculation with murine scrapie prions. In contrast, wild-type mice developed scrapie < 165 days after inoculation and most Prn-p0/+ mice, heterozygous for disruption of the PrP gene, exhibited signs of central nervous system dysfunction between 400 and 465 days after inoculation. In situ immunoblots showed widespread deposition of scrapie PrP (PrPSc) in the brains of both wild-type Prn-p+/+ and Prn-p0/+ mice, while neither cellular PrP (PrPC) nor PrPSc was detected in the brains of Prn-p0/0 mice. In contrast to Prn-p+/+ and Prn-p0/+ mice, Prn-p0/0 mice failed to propagate prion infectivity as measured by bioassays. Syrian hamster (SHa) PrP transgenes rendered Prn-p0/0 mice susceptible to prions containing SHaPrPSc. Immunization of Prn-p0/0 mice with purified, infectious mouse or SHa prions dispersed in Freund's adjuvant produced antisera that bound mouse, SHa, and human PrP on Western blots. Presumably, the lack of PrPC expression in Prn-p0/0 mice prevents them from becoming tolerant to the immunogen. The resistance of Prn-p0/0 mice to developing scrapie after inoculation with murine prions supports the hypothesis that PrPSc is essential for both transmission and pathogenesis of the prion diseases.

Animals↗
PubMed1993

Three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform.

To investigate the molecular basis of prion diversity, we inoculated transgenic mice expressing the Syrian hamster prion protein (PrP) with three distinct prion isolates. We compared the three isolates designated Sc237, 139H, and Me7H in Tg(SHaPrP)7 mice with clinical signs of scrapie because the incubation times with these mice are considerably shorter than the times found with hamsters. Each prion isolate produced a distinctive pattern of the scrapie isoform of PrP (PrPSc) accumulation, as determined by histoblotting, a technique developed for the regional mapping of PrPSc deposition. The PrPSc pattern with the Me7H isolate was particularly interesting because it appeared to be confined to the hypothalamus and related structures--including the interstitial nucleus of the stria terminalis, the paraventricular nucleus of the thalamus, and periaqueductal grey. Additionally, the regions of PrPSc accumulation remained highly restricted, even though the incubation time for Me7H scrapie was significantly longer than with Sc237 and 139H isolates. Neuropathological changes characterized by neuronal vacuolation and astrocytic gliosis were confined to those regions where PrPSc accumulated. These findings argue that the cell-specific propagation of prion isolates may be responsible for different properties exhibited by each of the isolates.

Animals↗
PubMed1993

Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes.

Transgenic mice expressing chimeric prion protein (PrP) genes derived from Syrian hamster (SHa) and mouse (Mo) PrP genes were constructed. One SHa/MoPrP gene, designated MH2M PrP, contains five amino acid substitutions encoded by SHaPrP, while another construct, designated MHM2 PrP, has two substitutions. Transgenic (Tg) (MH2M PrP) mice were susceptible to both Syrian hamster and mouse prions, whereas three lines expressing MHM2 PrP were resistant to Syrian hamster prions. The brains of Tg(MH2M PrP) mice dying of scrapie contained chimeric PrPSc and prions with an artificial host range favoring propagation in mice that express the corresponding chimeric PrP and were also transmissible, at reduced efficiency, to nontransgenic mice and hamsters. Our findings provide genetic evidence for homophilic interactions between PrPSc in the inoculum and PrPc synthesized by the host.

Animals↗
PubMed1993

Cytomegalovirus recurrence in seropositive pregnant women attending obstetric clinics.

To understand reasons for cytomegalovirus (CMV) recurrence, a cohort of 350 CMV-seropositive pregnant women attending obstetric clinics in Taiwan was examined for cervical or urinary CMV shedding. Urine specimens were collected from 350 women and cervical secretion specimens were collected from 220 women. We measured the association of various factors with CMV recurrence, which was defined as viral shedding identified by the presence of a CMV-specific gene sequence amplified by the polymerase chain reaction in seropositive individuals. CMV recurrence status was independently associated with a sexual activity composite variable, which was defined by three sexual activity indicators: age at first sexual intercourse, total years of sexual experience, and average frequency of sexual intercourse prior to pregnancy. Pregnant women with a history of genital tract infection were more likely than women without such history to experience cervical CMV recurrence. Similarly, pregnant women with previous urinary tract infections were more likely to experience urinary CMV recurrence. The findings indicate that multiple exposure to CMV by sexual activity prior to pregnancy is an important determinant of CMV recurrence during pregnancy.

Antibodies, Viral↗
PubMed1993

Effects of captopril on platelet cytosolic free Ca2+ concentrations and on suppression of cell proliferation in culture.

In order to investigate the feasibility of angiotensin converting enzyme inhibitors (ACEIs) in preventing the development of atherosclerosis and restenosis after coronary angioplasty and to study their mechanisms, we measured the platelet cytosolic free Ca2+ concentration ([Ca2+]i) and observed the effects of captopril on platelet [Ca2+]i in rabbits and also observed the inhibitive action on fibroblast proliferation in culture. The results showed that resting platelet [Ca2+]i,ADP- or thrombin-stimulated platelet elevation amplitude after administration of captopril (12.5 mg, twice daily) for 15 days were significantly reduced in comparison with those before administration. And captopril also significantly inhibited fibroblast proliferation or reduced 3H-thymidine (3H-TdR) incorporation in culture in a dose-dependent manner. These findings suggest that ACEIs are promising drugs to reduce restenosis incidence after coronary angioplasty and to prevent atherosclerosis as well as provide a new explanation for their effects of suppressing cell proliferation.

Animals↗
PubMed1993

Effects of long-term estradiol exposure on the hypothalamic neuron number.

Neuron density, volume of the area and total neuron number were measured in the medial preoptic area, anterior hypothalamic area and arcuate nucleus of the hypothalamus of young (6-month-old), middle age (14-month-old) and old (22-month-old) male and female rats. Intact male rats did not show neuron loss even in old age, while intact female rats manifested neuron loss in the medial preoptic area, anterior hypothalamic area and arcuate nucleus in old age. Long-term administration of estradiol benzoate to castrated male rats induced neuron loss in the anterior hypothalamic area and arcuate nucleus of the middle age group and in all three areas of the old age group. However, long-term ovariectomy could not prevent neuron loss in these hypothalamic areas in old age. The results suggested that estradiol can have a cumulative impact on the degree of neuron damage and simulate female-type age-related neuron loss in male rats and that there may be the possibility of an intrinsic aging process inducing neuron loss in female rats.

Animals↗