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Biomedical subjects

Lina Wang

Publications and source records attributed to Lina Wang.

At least 37 records · Page 2Linked to original sources

Anti-hepatitis B surface antigen IgG1 subclass is predominant in individuals who have recovered from hepatitis B virus infection, chronic carriers, and vaccinees.

Patterns of each IgG-specific subclass for hepatitis B virus (HBV) core antigen (anti-HBc) are remarkably different among individuals with different infection status, i.e., completely recovered or chronic carrier. Each of the IgG-specific subclasses of HBV surface antigen (anti-HBs) was tested for ELISA sensitivity using four commercially available hepatitis B surface antigen (HBsAg) kits and one self-prepared plate. The specificity in 18 serum samples obtained from chronic HBV carriers, recovered individuals, vaccinees and non-infected individuals was investigated. Differences in absorbance values were obtained by comparing results from these different plates. Data on the absorbance values of anti-HBs IgG subclasses obtained indicated that one to four subjects had a false-negative or false-positive result using the four commercial plates. Only the self-prepared plate demonstrated 100% specificity and sensitivity for anti-HBs subclasses. Moreover, the results indicate that anti-HBs subclass IgG1 was predominant in cured patients, chronic carriers and vaccinees. The samples from both chronic carriers and vaccinees exhibited a significantly higher concentration of total IgG and IgG1 than samples in recovered individuals (P<0.05).

Carrier State↗

Phylogenetic analyses of human rotavirus in central Taiwan in 1996, 2001 and 2002.

BACKGROUND: Rotavirus epidemiology information is required for gastroenteritis disease control and prevention. Information gathered about the serotype distribution of rotaviruses isolated in Taiwan is of crucial significance, before a licensed rotavirus vaccine is introduced. OBJECTIVES: The purpose of the present study is to investigate the epidemiological diversity of rotaviruses in Taiwan. STUDY DESIGN: A total of 51 stool samples taken from cases of acute gastroenteritis were collected from three teaching hospitals in central Taiwan in 1996, 2001 and 2002. The samples were subjected to RT-PCR tests of VP7 gene of the human rotavirus group A, B, C. RESULTS: A total of 16 stool samples were detected positive by RT-PCR and 10 were sequence analyzed and classified into G1, G3, and G9 types. Compared with other HRV strains: the sequences of CS96-40 of G1 are similar to MVD9816 (identity rate 97.15% and 96.09%, respectively, from Uruguay); the sequences of CS02-01 of G3 are similar to 98-B31 (identity rate 98.93% and 98.72%, respectively, from Japan); the sequences of CS01-05, CS01-06, CS01-07, CS01-09, CS01-13, CS02-02, CS02-03, CS02-04 are very similar to other established G9 rotaviruses sequences (identity rate 96.85-99.88%), especially between CS02-04 and SP2737 (from Japan) with an identity rate of 99.88% and 100% nucleotide and amino acid, respectively. Except for CS01-06 strain, it is VR3, but not VR5, VR7 or VR8, that found to be the most frequent mutated amino acid regions of VP7 in these strains. CONCLUSIONS: Our findings are the first to document the high prevalence of G9 HRV strains in Taiwan, and suggest the re-emergence of G3 strains in central Taiwan since 1991. Epidemiological surveys carried out in this study suggest genotype shifts from type G1 before 1996, to G9 in 2001 and 2002 and the re-emergence of G3 type in 2002.

Antigens, Viral↗

MSP8 is a non-essential merozoite surface protein in Plasmodium falciparum.

MSP8 is a recently identified merozoite surface protein that shares similar structural features with the leading vaccine candidate MSP1. Both proteins contain two C-terminal epidermal growth factor (EGF)-like domains, a glycosylphosphatidylinositol (GPI) anchor attachment sequence and undergo proteolytic processing. By double recombination, we have disrupted the MSP8 gene in P. falciparum 3D7 parasites, and confirmed integration by southern hybridisation and PCR. Western blot analysis of lysates from asynchronous cultures and isolated merozoites demonstrated the absence of MSP8 in two cloned knockout lines. There was no significant difference in growth rate observed between 3D7 and the cloned DeltaMSP8 lines. Thus, unlike MSP1, MSP8 is not required for asexual stage parasite growth and replication in vitro. Further analysis of the cloned lines showed that loss of MSP8 had no effect on the levels of expression of other merozoite surface proteins including MSP1-5, 7 and 10. Stage-specific immunoblots showed that MSP8 expression commences in late rings and extends throughout the rest of the erythrocytic life cycle in the 3D7 parent line, but is absent from all stages in the DeltaMSP8 transfectants.

Animals↗

Two novel adeno-associated viruses from cynomolgus monkey: pseudotyping characterization of capsid protein.

We demonstrated the presence of two adeno-associated viruses (AAVs), designated AAV10 and AAV11, in cynomolgus monkeys by isolating and sequencing the entire viral coding regions from the monkey DNA. AAV10 and AAV11 capsid proteins shared 84% and 65%, respectively, of amino acids with AAV2. A phylogenetic analysis of AAV capsid proteins showed that AAV10 and AAV11 resembled most AAV8 and AAV4, respectively. To characterize the capsid protein, we pseudotyped an AAV2 vector with the monkey AAV capsid proteins and examined the resulting pseudotypes AAV2/10 and AAV2/11, in comparison with the AAV2 vector, for their host ranges in cell lines and tissue tropism in mice. AAV2/10 and AAV2/11 transduced primate cells less efficiently than AAV2. Whereas AAV2 transduced undifferentiated C2C12 mouse myoblasts more efficiently than differentiated ones, AAV2/10 and AAV2/11 transduced the undifferentiated myoblasts less efficiently than differentiated ones. Three weeks after injection to the muscle of the hind legs, AAV2/10 and AAV2 induced transgene expression similarly, but AAV2/11 did not transduce the skeletal muscle. Six weeks after systemic administration, transduced vector DNA was detected by PCR in the liver and spleen of mice inoculated with AAV2, in the liver, heart, muscle, lung, kidney, and uterus of mice with AAV2/10, and the muscle, kidney, spleen, lung, heart, and stomach of mice with AAV2/11. Mouse antisera against capsid protein VP2 of the three AAVs neutralized the respective vector particles in a type-specific manner. The results indicate that AAV10 and AAV11 capsid proteins, which are antigenically distinct from each other and AAV2, are likely to determine their host ranges and tissue tropism that are different from AAV2s, suggesting that cynomolgus AAVs could provide a broader choice of pseudotype AAV vectors for gene therapy.

Amino Acid Sequence↗

Acute chagas' disease presenting with a suprasellar mass and panhypopituitarism.

Although intrinsic pituitary lesions are the most common cause of hypopituitarism, suprasellar masses can produce similar symptoms. The differential diagnosis of a suprasellar mass includes cystic lesions, tumors, granulomatous disease, and infection. The etiology is not always obvious, and despite extensive work-up, may remain elusive. A 28-year-old Mexican man presented with complaints of headache and weakness for two weeks duration. He became increasingly lethargic and an MRI revealed a two centimeter suprasellar mass. Testing of the hypothalamic-pituitary axis suggested panhypopituitarism. He was prescribed treatment with hydrocortisone, DDAVP, and levothyroxine. Open craniotomy and biopsy of the hypothalamus revealed marked inflammation with plasma cells, histiocytes, and small lymphocytes. Light microscopy revealed macrophage-contained leishmania-like organisms although results were not immediately available. Pathological data was consistent with acute infection by Trypanasoma cruzi. Despite supportive efforts, the patient expired two months after presentation. This case illustrates the difficulty of diagnosing and the potential rapid mortality of a suprasellar mass. Because of the wide consideration of etiologies, a tissue diagnosis is needed. However, as this case illustrates, a definitive tissue diagnosis is not always possible, even following biopsy during open craniotomy.

Adult↗

Oral immunization with a combination of Plasmodium yoelii merozoite surface proteins 1 and 4/5 enhances protection against lethal malaria challenge.

Oral immunization of mice with Escherichia coli-expressed Plasmodium yoelii merozoite surface protein 4/5 or the C-terminal 19-kDa fragment of merozoite surface protein 1 induced systemic antibody responses and protected mice against lethal malaria infection. A combination of these two proteins administered orally conferred improved protection compared to that conferred by either protein administered alone.

Administration, Oral↗

Orally delivered malaria vaccines: not too hard to swallow.

Vaccines offer efficient and cost-effective protection against a wide range of infectious diseases. Unfortunately, no effective vaccine is yet available against malaria, and this infection remains one of the most important causes of human morbidity and mortality in the developing world. Over the past two decades a number of candidate proteins for inclusion in a subunit vaccine have been identified. Malariologists believe that an effective malaria vaccine will need to include multiple proteins that induce protective immune responses against different stages of the Plasmodium life cycle. The construction of such multivalent vaccines is beset by considerable logistical difficulties, not least of which is how to deliver them to a population living in endemic areas. Compared with other routes of vaccine administration, oral delivery has several advantages that make it an attractive strategy for vaccine development. This review summarises the progress towards an oral vaccine delivery system for malaria and discusses the feasibility of this approach.

Administration, Oral↗

The proto-oncogene c-kit is expressed in leiomyosarcomas of the uterus.

OBJECTIVE: The proto-oncogene c-kit encodes for a 145-kDa transmembrane tyrosine kinase receptor. Interaction with its ligand, stem cell factor, is essential in the development of hematopoietic stem cells, mast cells, gametocytes, melanocytes, and interstitial cells of Cajal. C-kit expression has been identified in a number of different neoplasms that includes mastocytosis/mast cell leukemia, acute myeloblastic leukemia, seminoma/dysgerminoma, and gastrointestinal stromal tumors. This study examines c-kit expression in uterine endometrial stromal sarcomas, leiomyomas, and leiomyosarcomas using immunohistochemistry. METHODS: Archival tissue from 38 patients with the uterine mesenchymal tumors (16 leiomyosarcomas, 8 leiomyomas, 11 low-grade endometrial stromal sarcomas, and 3 high-grade endometrial stromal sarcomas) was stained with polyclonal antibody for c-kit. Modified avidin biotin (ABC) immunoperoxidase method was employed for antibody detection. Individual tumors were considered positive if more than 10% of the cells comprising the neoplasm displayed immunoreactive staining. Staining intensity was graded 1+ to 3+ and distribution graded as focal (10-30% of the cells), intermediate (30-60% of the cells), or diffuse (>60% of the cells). RESULTS: C-kit was positive in 12 (75%) of the 16 leiomyosarcomas. The staining was 3+ and diffuse in the majority of the positive tumors. C-kit expression was not detected in any of the 8 leiomyomas. Two of the 3 high-grade endometrial stromal sarcomas displayed c-kit positivity. Staining was diffuse and 3+ in both of these tumors. Expression of c-kit was observed in only 3 of the 11 low-grade endometrial stromal sarcomas. CONCLUSIONS: C-kit is expressed in uterine leiomyosarcomas and endometrial stromal sarcomas. Adjunctive diagnostic studies using c-kit may be useful in distinguishing leiomyosarcomas from benign leiomyomas in uterine tumors that offer uncharacteristic features. Furthermore, studies should investigate the prospect of treating these malignant tumors with tyrosine kinase inhibitors.

Adult↗

Apical location of a novel EGF-like domain-containing protein of Plasmodium falciparum.

Using bioinformatics analyses of the unfinished malaria genome sequence, we have identified a novel protein of Plasmodium falciparum that contains two epidermal growth factor (EGF)-like domains near the C-terminus of the protein. The sequence contains a single open reading frame of 1572bp with the potential to encode a protein of 524 residues containing hydrophobic regions at the extreme N- and C-termini which appear to represent signal peptide and glycosylphosphatidylinositol (GPI)-attachment sites, respectively. RT-PCR analysis has confirmed that the novel gene is transcribed in asexual stages of P. falciparum. Antibodies to the EGF-like domains of the novel protein are highly specific and do not cross-react with the EGF-like domains of MSP1, MSP4, MSP5 or MSP8 expressed as GST fusion proteins. Antisera to the C-terminal fragments react with two bands of 80 and 36kDa in P. falciparum parasite lysates whereas antisera to the most N-terminal fusion protein only recognises the 80kDa band, suggesting that the novel protein may undergo processing in a similar way to MSP1 and MSP8, but with fewer cleavage events. Immunoblot analysis of stage-specific parasite samples reveals that the protein is present in trophozoites, schizonts and in isolated merozoites. The protein partitions in the detergent-enriched phase after Triton X-114 fractionation and is localised to the surfaces of trophozoites, schizonts and free merozoites in an apical distribution. Based on the accepted nomenclature in the field we now designate this protein MSP10. We have shown that the MSP10 fusion proteins are in a conformation that can be recognised by human immune sera and that there is very limited sequence diversity in an approximately lkb region of MSP10, encompassing the two EGF-like domains. A sequence similar to MSP10 can be identified in the available P. yoelii genomic sequence, offering the possibility of ascertaining whether this novel protein can induce host protective responses in an in vivo model.

Amino Acid Sequence↗

Oral immunization with a recombinant malaria protein induces conformational antibodies and protects mice against lethal malaria.

The increasing death toll from malaria, due to the decreasing effectiveness of current prophylactic and therapeutic regimens, has sparked a search for alternative methods of control, such as vaccines. Although several single proteins have shown some promise as subunit vaccines against sexual blood stages in experimental systems, it is clear that multicomponent vaccines are required. Many logistic difficulties make such an approach prohibitively expensive. In an effort to try to overcome some of these issues, we examined the possibility of oral immunization as a route for inducing host protective immunity. We report here that oral feeding of a malaria protein induced serum antibody levels similar to those induced by intraperitoneal immunization with Freund's adjuvant. Further, responses to conformational epitopes were induced. In the rodent challenge system, significant levels of protection to lethal challenge with malaria were induced in mice. The protective efficacy was highly correlated with antibody levels, which depended on the antigen dosage and required cholera toxin subunit B as an oral adjuvant. These findings offer new approaches to the development of a malaria vaccine and provide justification for the investigation of transgenic plants as a means of vaccine delivery.

Administration, Oral↗

Coincident choroid plexus carcinoma and adrenocortical carcinoma with elevated p53 expression: a case report of an 18-month-old boy with no family history of cancer.

We describe a young patient with no known family history of cancer who presented at 18 months with 2 advanced primary tumors, choroid plexus carcinoma and adrenal cortical carcinoma. Immunohistochemical studies demonstrated high levels of nuclear p53 protein expression in both tumors, as well as in the adjacent normal-appearing adrenal cortical cell nuclei of the adrenal gland. The immunohistologic distribution of elevated p53 expression suggests that this individual has a de novo germline mutation affecting p53 gene expression.

Adrenal Cortex Neoplasms↗