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Biomedical subjects

A Mathew

Publications and source records attributed to A Mathew.

At least 55 records · Page 3Linked to original sources
PubMed1998

Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection.

We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221 to 232 on NS3. These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive.

CD4-Positive T-Lymphocytes↗
PubMed1998

Heat shock response and protein degradation: regulation of HSF2 by the ubiquitin-proteasome pathway.

Mammalian cells coexpress a family of heat shock factors (HSFs) whose activities are regulated by diverse stress conditions to coordinate the inducible expression of heat shock genes. Distinct from HSF1, which is expressed ubiquitously and activated by heat shock and other stresses that result in the appearance of nonnative proteins, the stress signal for HSF2 has not been identified. HSF2 activity has been associated with development and differentiation, and the activation properties of HSF2 have been characterized in hemin-treated human K562 erythroleukemia cells. Here, we demonstrate that a stress signal for HSF2 activation occurs when the ubiquitin-proteasome pathway is inhibited. HSF2 DNA-binding activity is induced upon exposure of mammalian cells to the proteasome inhibitors hemin, MG132, and lactacystin, and in the mouse ts85 cell line, which carries a temperature sensitivity mutation in the ubiquitin-activating enzyme (E1) upon shift to the nonpermissive temperature. HSF2 is labile, and its activation requires both continued protein synthesis and reduced degradation. The downstream effect of HSF2 activation by proteasome inhibitors is the induction of the same set of heat shock genes that are induced during heat shock by HSF1, thus revealing that HSF2 affords the cell with a novel heat shock gene-regulatory mechanism to respond to changes in the protein-degradative machinery.

Animals↗
PubMed1997

Plague pneumonia disease caused by Yersinia pestis.

Plague is a zoonotic infection caused by Yersina pesits, a pleomorphic, gram-negative non-spore-forming coccobacillus that is more accurately classified as a subspecies of Y pseudotuberculosis. Animal reservoirs include rodents, rabbits, and occasionally larger animals. Cats become ill and have spread pneumonic disease to man. Dogs may be a significant sentinel animal as well as a reservoir, although do not usually become ill. Flea bites commonly spread disease to man. Person to person spread has not been a recent feature until the purported outbreak of plague and plague pneumonia in India in 1994. Other factors that increase risk of infection in endemic areas are occupation-veterinarians and assistants, pet ownership, direct animal-reservoir contact especially during the hunting season, living in households with an index case, and, mild winters, cool moist springs, and early summers. Clinical presentations include subclinical plague (positive serology without disease); plague pharyngitis; pestis minor (abortive bubonic plague); bubonic plague; septicemic plague; pneumonic plague; and plague meningitis. Most prominent of plague's differential diagnosis are Reye's syndrome, other causes of lymphadenitis, bacterial pneumonias, tularemia, and acute surgical abdomen. Treatment has reduced mortality from 40-90% to 5-18%. The drug of choice (except for plague meningitis) is streptomycin, with tetracyclines being alternatives. Parenteral cholamphenicol is the treatment of choice for plague meningitis. A tetracycline should be administered as chemoprophylaxis to all contacts over the age of 8 years. Plague vaccine is available, but is only partially protective.

Animals↗
PubMed1996

Dominant recognition by human CD8+ cytotoxic T lymphocytes of dengue virus nonstructural proteins NS3 and NS1.2a.

A severe complication of dengue virus infection, dengue hemorrhagic fever (DHF), is hypothesized to be immunologically mediated and virus-specific cytotoxic T lymphocytes (CTLs) may trigger DHF. It is also likely that dengue virus-specific CTLs are important for recovery from dengue virus infections. There is little available information on the human CD8+ T cell responses to dengue viruses. Memory CD8+CTL responses were analyzed to determine the diversity of the T cell response to dengue virus and to identify immunodominant proteins using PBMC from eight healthy adult volunteers who had received monovalent, live-attenuated candidate vaccines of the four dengue serotypes. All the donors had specific T cell proliferation to dengue and to other flaviviruses that we tested. CTLs were generated from the stimulated PBMC of all donors, and in the seven donors tested, dengue virus-specific CD8+CTL activity was demonstrated. The nonstructural (NS3 and NS1.2a) and envelope (E) proteins were recognized by CD8+CTLs from six, five, and three donors, respectively. All donors recognized either NS3 or NS1.2a. In one donor who received a dengue 4 vaccine, CTL killing was seen in bulk culture against the premembrane protein (prM). This is the first demonstration of a CTL response against the prM protein. The CTL responses using the PBMC of two donors were serotype specific, whereas all other donors had serotype-cross-reactive responses. For one donor, CTLs specific for E, NS1.2a, and NS3 proteins were all HLA-B44 restricted. For three other donors tested, the potential restricting alleles for recognition of NS3 were B38, A24, and/or B62 and B35. These results indicate that the CD8+CTL responses of humans after immunization with one serotype of dengue virus are diverse and directed against a variety of proteins. The NS3 and NS1.2a proteins should be considered when designing subunit vaccines for dengue.

Adult↗
PubMed1996

Is oral cancer susceptibility inherited? Report of five oral cancer families.

All the oral cancer patients registered at the Regional Cancer Centre, Trivandrum, during January to July 1995 were subjected to detailed pedigree analysis. This revealed that oral cancer tends to aggregate in families. Like other familial cancers, a family history of oral cancer was associated mostly with an early age of onset of the disease. Family members without habits such as tobacco chewing, smoking or alcohol consumption were also affected. These observations prompt us to suggest the probable inheritance of an oral cancer susceptibility gene in these families. The familial aggregation, mostly site-specific, with an autosomal dominant mode of inheritance, was observed in 0.94% of the total oral cancers. This necessitates the need to undertake studies to elucidate the molecular lesions responsible for oral cancer susceptibility in families.

Adult↗
PubMed1995

Hsp-70 is closely associated with the transferrin receptor in exosomes from maturing reticulocytes.

The presence of the heat shock protein (hsp-70) has been detected in exocytosed vesicles (which are named exosomes) from mammalian and avian immature red cells (i.e. reticulocytes) as well as from a differentiating avian erythroleukaemic cell line. The close, but non-covalent, association of hsp-70 with the transferrin receptor (TFR) in exosomes is demonstrated by: (1) the ability to cross-link hsp-70 to TFR; (2) the co-immunoprecipitation of hsp-70 and TFR with an antibody against TFR, and the co-immunoprecipitation of TFR and hsp-70 with antibody against hsp-70; and (3) the retention of TFR by hsp-70 bound to ATP-agarose and the simultaneous elution of both proteins by excess ATP. Semi-quantitative analysis of the relative efficiency of cross-linking of these proteins in exosomes versus plasma membranes shows that TFR in exosomes is preferentially bound to hsp-70. From an analysis of the relative amounts of hsp-70 and TFR regenerated from the cross-linked complex, the ratio of TFR monomer bound to hsp-70 is approximately 1.5 to 1. Given the presence of hsp-70 in exosomes from several species and its close association with TFR (the major protein lost during reticulocyte maturation) it is proposed that hsp-70 plays a role in exosome formation and/or release in immature red cells.

Animals↗
PubMed1995

Optimum method for urinary drainage in major abdominal surgery: a prospective randomized trial of suprapubic versus urethral catheterization.

The outcome of suprapubic and urethral catheterization in abdominal surgery was compared in a prospective randomized trial. Twenty-eight patients received a suprapubic and 29 a urethral catheter. The groups were similar in terms of age, sex, operation performed and postoperative analgesia. There was no difference in the duration of catheterization (suprapubic: median 5 (range 4-10) days; urethral: median 4 (range 2-11) days). Urinary sepsis occurred in three patients in each group. Urethral catheters caused pain in significantly more patients (urethral 13; suprapubic two; chi 2 = 8.6, 1 d.f. P < 0.01), on more days (suprapubic: 6 of 142 catheter days; urethral: 37 of 126 catheter days; chi 2 = 29.5, 1 d.f. P < 0.001). Two men with urethral catheters and one with a suprapubic catheter failed to void urethrally when required to do so. Suprapubic catheterization is the method of choice for urinary drainage when this is required in abdominal surgery.

Abdomen↗
PubMed1995

Implications of gynaecological abnormalities in pre-selection criteria for cervical screening: preliminary evaluation of 3602 subjects in south India.

Early detection and eradication of cervical cancer and its precursor lesions through organized mass cytological screening programmes have recently gained considerable attention in developing countries. Strategies for both cost saving and effective implementation are however required for mass cervical screening in developing countries. In an early cancer detection programme conducted in South India, we analysed cytological abnormalities in 3602 women and correlated the results with other factors, including age, gynaecological complaints, number of years of married life and parity to see if pre-selection for cytologic screening was possible. Only lower grades of dysplasia were found in asymptomatic women below the age of 40 years. In asymptomatic women, malignancy and higher grades of dysplasia were confined to women with a clinically abnormal cervix only. Univariate analysis also revealed that subjects with a parity of more than 3 and a married life of more than 20 years had a significantly higher number of cytological abnormalities. However, on a multivariate analysis the increased number of marital years was not found to be an independent variable. These results suggest that asymptomatic women below the age of 40 years with a married life of less than 20 years and parity below 3, may be excluded from screening campaigns, and that pre-selection for cytologic screening is possible by introducing a programme of clinical and speculum examination of the cervix.

Adult↗
PubMed1994

Skin manifestation of agnogenic myeloid metaplasia.

Agnogenic myeloid metaplasia (AMN) with myelofibrosis is a clonal malignancy of the hematopoietic stem cell. The disease is characterized by increased endothelial cell and fibroblast proliferation, resulting in increased deposition of fibronectin, laminin, and collagen in the bone marrow. In advanced disease, extramedullary hematopoiesis (EMH) is invariably seen in the spleen and liver. The lymph nodes are also frequent sites of EMH, but other organs, especially the kidneys, arenals, lungs, pleura, ovaries, gastrointestinal tract, and dura, may also be involved. Skin manifestations are rare. They may present in several ways: erythematous plaques, nodules, diffuse or papular erythema, ulcers, and bullae. Histopathology of these lesions reveals cells from one or more myeloid lineage in the dermis, erythroid, or megakaryocytic series alone or in combination. In rare cases, all three cell lines are demonstrated.

Aged↗
PubMed1994

Jack fruit lectin-specific glycoconjugate expression during the progression of cervical intraepithelial neoplasia: a study on exfoliated cells.

The expression of glycoconjugates specific to Jack fruit lectin (JFL) was studied in the exfoliated squamous cells of different grades of intraepithelial and invasive neoplasia of the uterine cervix. It was observed that while normal cells showed almost negative binding, the lectin binding percentage of squamous cells significantly increased with increasing atypia of the epithelium. Correlation analysis between different groups revealed that mild lectin binding in cells had a negative correlation and intense binding had a positive correlation with various stages of tumor progression. These results indicate that the number of cells with aberrant expression of glycoconjugates increases as neoplastic transformation advances. The percentage of labeled and unlabeled cells also shows a continuous transition from low to severe grades of cervical intraepithelial neoplasia and invasive carcinomas. The present study therefore shows that JFL may be used as a probe for further elaboration of detection and grading of precancerous and cancerous lesions of the uterine cervix.

Female↗
PubMed1994

Serum IgA cross-reactivity between glycine-alanine repeat sequence of EBNA-1 and keratin or collagen in nasopharyngeal carcinoma.

Inhibition studies were carried out to study possible cross-reactivity between a peptide fragment of the Epstein-Barr virus nuclear antigen, EBNA-1, and keratin/collagen. The 20-amino acid peptide (pAG), derived from a glycine-alanine repeat region of EBNA-1, uniquely makes up about one-third of the viral protein and is a dominant IgA antigenic epitope in patients with nasopharyngeal carcinoma (NPC). A small percentage of normal human sera (NHS) also binds pAG and this reactivity is examined in this study. Ten percent (2/20) and 13.4% (2/15) of IgA-pAG-positive NPC sera and NHS, respectively, were significantly inhibited by keratin in a competitive ELISA system. Conversely, 31.6% (6/19) and 30.8% (4/13) of IgA-keratin-positive NPC sera and NHS, respectively, were significantly inhibited by pAG. This indicated minimum cross-reactivity between IgA serum antibodies to EBNA-1 and keratin. Using collagen as inhibitor, none of 18 and only 2/13 IgA-pAG-positive NPC sera and NHS, respectively, were inhibited. In the collagen ELISA system, only 2/19 (10.5%) and 4/25 (16%) of IgA-collagen-positive NPC sera and NHS, respectively, were inhibited with pAG. Therefore, cross-reactivity with collagen was also low. IgA-pAG-positive NHS may therefore not be a false positive phenomenon, but whether it may represent an early serological profile related to NPC carcinogenesis remains to be determined.

Alanine↗
PubMed1994

A high incidence of serum IgG antibodies to the Epstein-Barr virus replication activator protein in nasopharyngeal carcinoma.

The BamHI Z EBV replication activator (ZEBRA) protein is involved in the switch from latency to productive cycle of Epstein-Barr virus. A recombinant ZEBRA protein was synthesized and assessed in enzyme-linked immunosorbent assay (ELISA) for serum IgG response in nasopharyngeal carcinoma (NPC) patients. In 100 NPC serum samples that were positive for IgA to the EBV viral capsid antigen (VCA), 75% had IgG anti-ZEBRA antibodies. In contrast, only 3/83 (3.6%) serum samples from healthy donors and 2/50 (4%) from other cancers were positive for IgG to ZEBRA. Interestingly, in a selected group of 100 NPC sera negative for IgA to VCA, 25% contained IgG anti-ZEBRA antibodies. This suggests that the ELISA for IgG anti-ZEBRA may also identify earlier cases of NPC not detected by the conventional immunofluorescence test for IgA to VCA.

Antibodies, Viral↗
PubMed1994

Loss of glucose transporters is an early event in differentiation of HD3 cells.

The HD3 cell, a chicken erythroblast cell line infected with a temperature-sensitive avian erythroblastosis virus, becomes committed to differentiate to an erythrocyte upon temperature shift in presence of inducers. Before induction, the HD3 cell transports glucose and 2-deoxyglucose (2-DG). 3-O-methylglucose is poorly taken up. Upon induction of differentiation, glucose and 2-DG transport activity fall. Twenty-four hours postinduction, up to 75% of the glucose transport activity may disappear. By use of cDNA probes for chicken glucose transporters, two species of mRNA of 3.1 and 1.7 kb (equivalent to mammalian GLUT1 and GLUT3 mRNA, respectively) are detected. Both messages virtually disappear within 48 h after induction. Run-on assays show the cessation of synthesis of the corresponding RNAs parallel to the loss of glucose transport. In contrast to the glucose transporters, the nucleoside transporter level increases after induction of hematopoiesis. This developmental pattern is consistent with earlier studies showing that mature chicken erythrocytes have little glucose transport activity but retain appreciable levels of the nucleoside transporter and that nucleosides and glutamine provide major sources of oxidizable carbon compounds to sustain metabolism in circulating chicken erythrocytes.

3-O-Methylglucose↗
PubMed1993

Expression and loss of the transferrin receptor in growing and differentiating HD3 cells.

During induced differentiation and maturation of HD3 cells (a chicken erythroblast cell line infected with a temperature-sensitive mutant of the avian erythroblastosis virus), the levels of transferrin receptor (TFR) and nucleoside transporter increase. Both these activities increase before elevated levels of hemoglobin are detected. Shortly after induction, as cellular TFR levels rise, a native-size TFR is detected in the cell-free culture medium, associated with an exosome fraction (100,000 xg pellet). Nucleoside transporter (measured as NBMPR-binding activity) is not increased in this pellet with induction. Previous studies have suggested that exosome formation in peripheral reticulocytes may be a significant route for loss of specific membrane proteins (Johnstone et al., 1991). Although the present experiments in HD3 cells do not address the quantitative importance of exosome formation, the studies suggest that exosome formation is an early event in commitment to the red cell lineage and is not a phenomenon restricted to the terminal stages of red cell maturation.

Adenosine Triphosphate↗