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Biomedical subjects

U Prasad

Publications and source records attributed to U Prasad.

18 recordsLinked to original sources

Descriptive epidemiology of nasopharyngeal carcinoma in Peninsular Malaysia.

Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Malaysia, a country in Southeast Asia with a multiracial population. While hospital-based data on NPC and data from a few states have been reported, a comprehensive study involving every known NPC patient in the whole of Peninsular Malaysia in one particular year had never been done. In the present study, the computed incidence rate was not only adjusted for age, sex, ethnicity, and place of residence, but also direct standardization methods of Rothman and Dever were used to reduce any distortion. The mean age of the 365 new cases of NPC registered in 1988 was 46.8 years (SD +/- 12.2 years). The ages of patients ranged from 10 to 80 years. The incidence in both sexes rose after the age of 20-29 years and reached a plateau between 40 and 49 years. No further rise was exhibited after age 60 years. The Chinese had the highest age-adjusted incidence rates, particularly for the age group 40-49 years, where the incidence rate was 40.1 per 100,000 for males and 14.9 for females. The average age-adjusted male/female ratio was 2.8:1. Age-adjusted incidence varied by place of residence. The pattern that emerged from the data indicated the possibility of interaction between genetic susceptibility and environmental cofactors in the etiology of NPC.

Adolescent

Expression of Epstein-Barr virus genes and of lymphocyte activation molecules in undifferentiated nasopharyngeal carcinomas.

Previous studies investigating the role of Epstein-Barr virus (EBV) in undifferentiated nasopharyngeal carcinoma (NPC) have been performed on extracts from biopsies. The authors analyzed expression and localization of viral gene products in 18 undifferentiated NPCs at the cellular level using immunohistology and in situ hybridization. All cases were EBV-positive. The small nuclear EBV-encoded RNAs, EBERs, were regularly expressed whereas the latent membrane protein, LMP1, and EBV was detectable only in four cases (22%) and the nuclear antigen 2 was not detectable. The BZLF-1 protein of EBV which disrupts viral latency, was not detectable, confirming that the virus is latent in the tumor cells. Although the expression of the CD23 antigen in transplantable NPCs has been reported, our study demonstrates that expression of this antigen in human undifferentiated NPCs is rare. In contrast, almost all cases expressed the CDw70 antigen. Since in normal tissues this antigen is present only in activated lymphoid blasts, this finding may be relevant for the differential diagnosis of undifferentiated NPCs.

Antibodies, Monoclonal

Salivary and serum IgA antibodies to the Epstein-Barr virus glycoprotein gp340: incidence and potential for virus neutralization.

Human antibody responses to the Epstein-Barr virus (EBV) glycoprotein gp340 have been measured using purified preparations of the native molecule as the substrate in ELISAs. This glycoprotein is the dominant component of the EBV envelope and a major target for the virus-neutralizing antibody response. Healthy virus carriers (both Caucasian and Chinese) regularly show detectable anti-gp340 IgG in serum and, unexpectedly, 21-30% of these individuals are also serum anti-gp340 IgA positive. Chinese patients with the EBV-genome-positive malignancy nasopharyngeal carcinoma (NPC) show elevated serum IgA antibodies to gp340 but, given the background of responses amongst healthy virus carriers, anti-gp340 IgA titres are a poorer diagnostic indicator of NPC than serum IgA antibodies detectable by immunofluorescence against the multicomponent EBV early antigen (EA). Salivary IgA antibody responses to gp340 are potentially important as a means of neutralizing orally-transmitted virus. We detected salivary IgA (but not IgG) to gp340 in a minority (12-19%) of healthy virus carriers and in a higher proportion (49%) of NPC patients. Even saliva samples chosen for their relatively high anti-gp340 IgA titres showed only weak neutralizing activity against transforming EBV preparations whether from B95.8 cell culture supernatant or from the throat washing of an infectious mononucleosis patient. We conclude that in healthy virus carriers, salivary IgA responses to gp340 are unlikely to provide effective local immunity against re-infection with a second EBV strain.

Adult

Epstein-Barr virus nuclear antigen 1 linear epitopes that are reactive with immunoglobulin A (IgA) or IgG in sera from nasopharyngeal carcinoma patients or from healthy donors.

The entire amino acid sequence of the unique region of the EBNA 1 protein was synthesized as a set of 41 20-residue peptides with an overlap of 10 amino acids. The peptides were tested in the enzyme-linked immunosorbent assay for reactivity with immunoglobulin A (IgA) and IgG in sera from 50 patients with nasopharyngeal carcinoma (NPC) as compared with 36 serum samples from healthy Epstein-Barr virus (EBV)-seropositive donors and 5 serum samples from EBV-negative donors. The most immunoreactive peptide for both IgA and IgG binding was localized to the glycine-alanine repeat domain of the antigen. In the unique regions, 16 immunoreactive peptides were found. Of these, four were reactive with IgG but not IgA and three peptides were reactive with IgA but not IgG in NPC sera. In addition, several IgA and IgG epitopes on the carboxy-terminal region were specifically reactive with NPC sera, but unreactive with sera from healthy EBV-positive donors. The results suggest that EBV serology specific for individual epitopes may provide additional useful information not available by conventional serology with whole antigens or the EBNA complex.

Amino Acid Sequence

Expression of the Epstein-Barr virus BamHI A fragment in nasopharyngeal carcinoma: evidence for a viral protein expressed in vivo.

A family of mRNAs that are transcribed rightward through the BamHI A fragment have been detected in C15, a nasopharyngeal carcinoma (NPC) which has been passaged in nude mice. Northern (RNA) blot hybridizations indicate that these RNAs are also expressed in three other NPCs which have been established in nude mice and in an NPC obtained at biopsy. Moreover, hybridization in situ detected transcription from BamHI A in 12 NPCs and 1 Epstein-Barr virus (EBV)-containing carcinoma of the parotid gland. In each case, transcription was detected in all of the malignant epithelial cells. Transcription was not detected in two cases of EBV-positive lymphoma biopsies by in situ hybridization nor in latently infected EBV-positive lymphoblastoid cell lines by Northern blot hybridization. The consistent transcription of these sequences in latently infected epithelial malignancy but not in lymphoid cells suggests that this viral function is associated with latent EBV infection of epithelial cells. Sequence analysis of a cDNA synthesized from the C15 tumor, representing the 3' end of BamHI A messenger RNA, revealed an open reading frame (ORF). Translation of this ORF in vitro produced several peptides that were immunoprecipitated with antisera from patients with NPC. The detection of antibodies to the protein encoded by the ORF present in the BamHI A cDNA indicates that BamHI A encodes a protein which is expressed in vivo and is antigenic.

Animals

Optic nerve involvement in nasopharyngeal carcinoma.

Five rare cases of nasopharyngeal carcinoma with optic nerve involvement are reported. Computerised Tomographic Scan (CT Scan) studies were performed in four of them. Evidence of intracranial spread of the tumour, from the roof of the fossa of Rosenmuller to the apex of the orbit through the cavernous sinus, was noted in three patients. In one of them there was extracranial extension of the tumour, to the orbit through the posterior ethmoid.

Adult

Serum and salivary IgA antibodies against a defined epitope of the Epstein-Barr virus nuclear antigen (EBNA) are elevated in nasopharyngeal carcinoma.

The Epstein-Barr virus nuclear antigen I (EBNA I) is the only latent EBV antigen consistently expressed in malignant tissues of the nasopharynx. A 20-amino-acid synthetic peptide, p107 contains a major epitope of EBNA I. We tested sera from 210 patients with nasopharyngeal carcinoma (NPC) and from 128 normal individuals (NHS) for IgA antibodies to p107 using an enzyme-linked immunosorbent assay (ELISA). Whereas 191/210 (91%) of NPC patients had IgA antibodies to p107, only 17/128 (13.3%) of NHS had such antibodies and only 6/57 (10.5%) of sera from patients with malignancies other than NPC had IgA-p107 reactivity. Thirty-nine salivary samples from 46 NPC patients (84.8%) also contained IgA-p107 antibodies whereas only 3/42 (7.1%) of normal saliva samples were IgA-p107 positive. The results suggest that IgA antibodies to EBNA I may become a useful, easily measurable, marker for NPC.

Adult

Detection of Epstein-Barr virus DNA in nasopharyngeal carcinoma using a non-radioactive digoxigenin-labelled probe.

The presence of Epstein Barr virus (EBV) DNA in biopsies from the post-nasal space (PNS) of patients suspected of nasopharyngeal carcinoma (NPC) was detected by in situ cytohybridization with an EBV DNA probe labelled with the novel labelling compound digoxigenin. The digoxigenin probe was hybridised to cryostat sections of NPC biopsies and subsequently detected by an enzyme immunoassay procedure. It was found that in situ cytohybridization using the digoxigenin probe was much more rapid and sensitive (96 h compared to five weeks) than the current method of using 3H-labelled probe. Using the digoxigenin EBV probe, it was found that in all the eighteen NPC biopsies tested, EBV DNA was detected in malignant epithelial cells and infiltrating lymphocytes. EBV DNA was also detected in some normal epithelial cells in these NPC biopsies. EBV DNA was not detected in epithelial cells of non-malignant biopsies.

Cell Line

Ultrastructural studies on the replication of herpes virus ateles-73 in owl monkey kidney cells.

The replicative cycle of herpesvirus ateles, strain 73 (HVA-73), was examined in the electron microscope and compared to that of other herpesviruses known to be oncogenic. A relatively slow replicative cycle of HVA-73 in owl monkey kidney (OMK) cells allowed us to distinguish cytoplasmic and nuclear stages of replication, comprising virus uptake, transport, maturation, and extrusion. Virus uptake was observed within 10 hours of infection and occurred both as a result of fusion between virus and cell membranes and by phagocytosis. Morphologic evidence for the transfer of viral DNA from nuclecapsids to the nucleus at the nuclear membrane is presented. This is shown by the location of numerous empty capsids in front of nuclear pores early during infection. Towards the end of the eclipse phase, at about 48 hougs after infection, two different types of nuclear inclusion bodies were observed. Progeny nucleocapsids were detected in the nucleus at the same time. The envelopment of nucleocapsids occurred both at the nuclear membrane and at proliferating Golgi lamellae in the cytoplasm. Each site of envelopment is associated with the maturation of a characteristic, morphologically distinguishable virus particle. The assembly of HVA-73 resembled that of other oncogenic herpesviruses.

Adsorption

Intracisternal tubular inclusions in nasopharyngeal carcinoma.

Biopsy specimens obtained from 20 cases of nasopharyngeal carcinoma were examined under electronmicroscope for the presence of Intracisternal Tubular Inclusions (ITI). In eight (40 per cent) of them these inclusions could be identified. Although the morphogenesis and significance of these ITI are not clearly understood, they have been found in several autoimmune and viral diseases, including infectious mononucleosis, a disease caused by EBV, and Burkitt's lymphoma, which is closely associated with EBV. Hence, the presence of ITI in NPC, another disease associated with EBV, seems to be of some significance. It is proposed that these inclusions could be the result of an immunological reaction initiated by injured cells infected with EBV, which acted as an antigen. The presence of another type of cytoplasmic inclusion, hitherto unknown, has also been reported.

Carcinoma

Recent data and significance of intracisternal tubular inclusions in human and animal cells.

In 24 out of 60 patients with nasopharyngeal carcinoma (NPC) the cells were shown to contain a tubulo-reticular network in the dilated cisternae of the ergastoplasm which corresponds to the entity described previously as "intracisternal-tubular inclusion" (ITI). The significance of such inclusions is discussed in different pathological conditions and the literature is reviewed. This is the first report of such inclusions in nasopharyngeal carcinoma.

Animals

Nasopharyngeal carcinoma and histocompatibility antigens.

New data are presented concerning the relationship between NPC and HLA antigens among Chinese. When attention is confined to newly diagnosed cases, it can be shown that, apart from the increased risk associated with the joint occurrence of A2 and B-Sin 2, there is also an increased risk associated with BW17 and a decrease in risk associated with A11. Among long-term survivors, however, BW17 is appreciably decreased, whereas A2 in the absence of B-Sin 2 or BW17 is increased. Among Malays, a non-Chinese group, there is an excess among NPC patients of a locus A blank, a blank which is probably associated with the AW19 complex.

Carcinoma

Nasopharyngeal craniopharyngioma.

Two cases of cranipharyngiomas which were mainly located in the nasopharynz have been reported. The cystic nature of the tumour with leakage of brownish-coloured fluid helped in arriving at the diagnosis, which was confirmed on histology. Marsupulization through a transpalatal approach seems to be the treatment of choice in such cases.

Angiography