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S Hsia

Publications and source records attributed to S Hsia.

At least 19 recordsLinked to original sources
PubMed1998

Intercellular and intracellular events following the MHC-unrestricted TCR recognition of a tumor-specific peptide epitope on the epithelial antigen MUC1.

We examined the functional and molecular parameters involved in direct TCR recognition of a tumor-specific peptide epitope on the tumor Ag MUC1. This peptide epitope is tandemly repeated and recognized on the native molecule rather than processed and bound to the MHC. Even though the TCR was not MHC restricted, intercellular interactions found to facilitate this recognition included intercellular adhesion molecule-1/LFA-1, LFA-3/CD2, and class I/CD8. Intracellular parameters of MHC-unrestricted CTL activation were examined to compare the recognition of the MUC1 epitope presented on synthetic microspheres, with the recognition of the native epitope in the context of other molecules on the target cells. The epitope on microspheres induced a transient influx of Ca2+ that was not accompanied by detectable tyrosine phosphorylation of the zeta-associated protein ZAP-70, whereas recognition of MUC1 epitopes on tumor cells caused a sustained Ca2+ influx and ZAP-70 phosphorylation. The transient influx of Ca2+ was not sufficient to cause translocation of the nuclear factor of activated T cells (NF-AT) into the nucleus or CTL proliferation. In contrast, recognition of the MUC1 epitope on tumor cells resulted in full activation of the CTL, nuclear translocation of NF-AT, and proliferation. MHC-unrestricted TCR triggering, therefore, involves similar intercellular and intracellular events that participate in the conventional, MHC-restricted Ag recognition. Direct recognition of the MUC1 peptide epitope by the TCR in the absence of presentation by the MHC induces a partial signal that is completed by further interactions of other receptor/ligand pairs on the surface of the CTL and their target cells.

Amino Acid Sequence↗
PubMed1998

En bloc transplantation of infant kidneys: ten-year experience.

BACKGROUND: Recent data have shown that en bloc infant kidneys transplanted to adult recipients functioned well. Longterm graft survival and function are not available, however. This study analyzes the 10-year experience with transplantation of en bloc infant kidneys from 1987-1997. STUDY DESIGN: This is a chart review of adult recipients of en bloc infant kidneys with respect to donors' and recipients' age, weight, creatinine, HLA antigen matching, panel reactive antibodies, cold ischemia time, surgical complications, original disease, and longterm graft function and survival. RESULTS: Five en bloc kidneys thrombosed (6.4%). Two ureteral fistulas were repaired successfully. Five patients underwent dialysis (6.4%). Two patients died of infection, six of heart attack and stroke, and one of cancer. All had excellent graft function at patients' death. Renal artery stenosis was dilated in seven patients. Six grafts were lost to rejection (one from noncompliance at 20 months). The original disease recurred in three patients with massive proteinuria despite excellent function. Graft survival at 43 months (range, 6-123 months) was 79%, with serum creatinine levels at 1, 3, 9 and 10 years of 1.2, 1.0, 0.8 and 0.8 mg/dl, respectively. Creatinine clearance averaged 88 mL/min (range, 34-188 mL) and 24-hour proteinuria was 146 mg (normal range, 10-150). CONCLUSIONS: In conclusion, en bloc infant kidneys can be transplanted successfully with excellent longterm function, hyperfiltration injury was not observed, and infant kidneys should be used more frequently.

Adult↗
PubMed1997

Elevated soluble interleukin 2 receptor levels found among kidney transplant recipients.

Although previous studies have not demonstrated a clear correlation between interleukin (IL) 2 receptor levels and immunological events after transplantation, many still suggest that these levels have clinical utility. A total of 759 serial measurements of both IL-2R and creatinine were compared over time and correlated with rejection episodes, clinical course, and immunosuppression. The profiles for the 40 patients showed several patterns, including correlation with changes in creatinine levels or with renal dysfunction, peaks in the absence of clinical findings, and discordant IL-2R and creatinine levels. Wide baseline variations in IL-2R levels confounded comparison of mean values and definition of a statistically significant rise. While tending to correlate with immunological events, elevations in IL-2R also occurred in clinically normal patients. IL-2R appears to lack specificity for immunological events. Thus, we conclude that IL-2R measurement does not have clinical diagnostic utility for monitoring renal transplant recipients.

Cadaver↗
PubMed1995

The quantitation of altered hepatic foci during multistage hepatocarcinogenesis in the rat: transforming growth factor alpha expression as a marker for the stage of progression.

The experimental three-stage hepatocarcinogenesis protocol of initiation, promotion, and progression, coupled with the analytical technique of stereology, permits quantitative analysis of the carcinogenic process, including the derivation of biologically based risk assessment models. The aberrant expression of the placental isozyme of glutathione S-transferase (PGST) is an efficient marker for initiated, preneoplastic, and neoplastic hepatocytes. Putatively initiated cells and their clonal progeny can be identified, enumerated, and their growth characteristics determined on the basis of their aberrant expression of this protein. A lack of suitable markers has made the identification and quantitation of hepatocytes in the early stage of progression more difficult. One characteristic of cells in the stage of progression is the evolution of relatively autonomous growth. The alteration of growth factor signalling pathways may provide one mechanism for this observation. The expression of transforming growth factor alpha (TGF alpha) is seen in many malignancies. The initiation-promotion-progression protocol has been used to induce progression in the rat liver. The focal expression of TGF alpha was found to correlate with areas of progression in rats subjected to this protocol. The ability to identify and quantitate cells in the stage of progression should facilitate application of the Moolgavkar-Venzon-Knudson model for assessing human risk from carcinogens active at each of these three stages. Validation of this model will require determination of the number and growth characteristics of hepatocytes in the stage of progression.

Animals↗
PubMed1995

Growth and function of en bloc infant kidney transplants: a preliminary study.

We evaluated the growth and function of 21 pairs of en bloc infant kidneys transplanted into adult recipients. Serum creatinine, 99mtechnetium-diethylenetriaminepentaacetic acid glomerular filtration rates, kidney volumes and resistive indexes were determined at 1 to 3, 3 to 6 and beyond 6 months, and compared using repeated measures analysis of variance tests. En bloc kidneys grew at a statistically significant rate (p < 0.001), for example nearly 2-fold in 3 to 6 months (209 +/- 69 cc from 132 +/- 70 cc), and approaching 3-fold at 6 months and longer (325 +/- 106 cc). Similarly, the glomerular filtration rates increased almost 4-fold (83 +/- 52 ml. from 23 +/- 11 ml. per minute) and 5-fold (121 +/- 45 ml., p < 0.001), respectively, during the same periods. Resistive indexes remained at normal range (0.60 to 0.63). Recipient blood pressure was normal. Our study shows that infant en bloc kidney transplants grow rapidly and provide excellent function to the adult recipient.

Adult↗
PubMed1994

Heteroduplexes for HLA DQB1 identity of family members and kidney donor-recipient pairs.

DNA heteroduplex (HD) electrophoretic patterns of DQB1 alleles from 124 individuals (38 members from 7 families and 43 kidney donor-recipient pairs) were analyzed in reference to each individual's DQB1 diallelic types determined by the polymerase chain reaction-RFLP method. The assignment of DQB1 homozygosity and heterozygosity, based solely on HD patterns, was accurate and correlated well with the typing results. DQB1 homozygotes invariably gave HD patterns of a single band while heterozygotes gave HD patterns of multiple bands. Distinct HD patterns of 2 heterozygotes predict the presence of at least 1 different DQB1 type between the pair. However, pairs with identical HD patterns may have different subtypes, because HDs with 1 or 2 nucleotide differences may sometimes give an identical HD pattern. Because of its simplicity and reproducibility, this HD analysis protocol serves as an excellent alternative to screen for DQB1 homozygotes and mismatched tissue donor-recipient pairs. This protocol is also useful for confirming the correctness of DQB1 allelic type assignments in a clinical setting.

Alleles↗
PubMed1994

Renal transplantation at Allegheny General Hospital with special reference to the use of extreme-age cadaveric donors.

We report our experience with 25 living-donor and 427 cadaveric-donor kidneys followed for over 6 years. Patient survival exceeds 90% at 5 years for all recipients. Overall one-year and 5-year graft survival rates were 82.7% and 65.5%, respectively. Approximately one-third of CAD were of extreme age (eg, < or = 10 and > or = 60 years old). One-year and 5-year GS rates of this group were 72.2% and 54.8%, respectively. Kidneys from elderly donors probably should be given to age-matched recipients. Infant en bloc kidneys had good GS. They also adapted well their growth and function to adult recipients and should be used more frequently to alleviate the organ shortage problem. HLA mismatches, transplant PRA level, original kidney disease, and immunosuppressive regimens significantly affected the GS. Race, sex, cytomegaloviral antibody states, unacceptable antigens, length of pretransplant dialysis, and CAD cold ischemic time had no significant effect on GS.

Adolescent↗
PubMed1993

Molecular compatibility and renal graft survival--the HLA DQB1 genotyping.

Renal donor-recipient HLA DQB1 typing at the DNA level provides a new avenue to study graft survival (GS) and compatibility. HLA DQB1 genotypes of 63 renal donor-recipient pairs were typed simultaneously by assessing patterns from electrophoresed restriction fragments (PCR-RFLP) of amplified DNA (ADNA) and hybridization patterns of sequence specific oligonucleotides (PCR-SSO) of ADNA. Thus the clinical applicability of these two protocols for HLA DQB1 typing was assessed in addition to the compatibility study. Typing results of these two protocols gave overall agreeable results. Sixty-seven per cent of 150 alleles from 75 heterozygotes typed by both protocols had identical allelic type assignments. Serotyping shared more concordant results to PCR-RFLP determined types than to PCR-SSO determined types. The PCR-RFLP protocol can be easily implemented for clinical DNA typing because of its clarity in assigning allelic types and the possible handling of a small number of typing samples, even a single sample, in a single run. The degree of compatibility of these donor-recipient pairs was measured by matching (M) or mismatching (MM) the PCR-RFLP determined DQB1 allelic types. The Kaplan-Meier method was used to estimate GS. Significantly higher GS rates (P < 0.03) were found in donor-recipient pairs with 2 M (GS:74%) as compared with those with 1 M (GS:68%) or 0 M (GS:40%). Higher graft survival was also associated with 0 MM (GS:86%) compared with those with 1 MM (GS:60%) or 2 MM (GS:40%), although the significance level is P = 0.08 for both Mantel-Cox and Breslow tests. These findings indicate the importance of determining HLA DQB1 molecular alleles for assessing GS.

Alleles↗
PubMed1993

Molecular compatibility and renal graft survival--the HLA DRB1 genotyping.

HLA DRB1 allelic types were determined by using sequence-specific oligonucleotides for the analysis of 91 renal donor-recipient pairs that were followed for 30 months. The Kaplan-Meier method was used to evaluate graft survivals (GS) of the matched and mismatched groups. The degree of compatibility was measured by allelic type matches and mismatches of the pairs. Furthermore, HLA DR genotypes were categorized into five groups, namely DR1, DR2, DR4, the group that also has the DRw52 allele, and the group of DR7, DR9, and DR10. All types within a group were considered a match. Serotypes of the same study group were also included for comparison. Associations of superior GS with compatible DRB1 allelic types, serotypes, and grouped DRB1 types were observed. A significantly higher GS rate was found in donor-recipient pairs when HLA DRB1 types were analyzed by group mismatching (P = 0.03) rather than type mismatching (P > 0.34). Because of the numerous allelic types that can be assigned on the basis of nucleotide sequence variations, a larger number of donor-recipient pairs is required to derive statistically significant results.

Adult↗
PubMed1986

Natural killer cell activity and antibody dependent cell-mediated cytotoxicity in preeclampsia.

Natural killer cell activity and antibody dependent cell-mediated cytotoxicity (NK and ADCC) of peripheral blood lymphocytes were measured against K-562 and antibody coated HSB target cells with a 4-h chromium release assay in 19 primigravidas with preeclampsia. Nineteen primigravidas with an uncomplicated pregnancy and 19 nonpregnant women served as controls. Lymphocyte NK and ADCC activities are significantly lower in primigravidas than in nonpregnant women. Primigravidas with preeclampsia have similar cell-mediated cytotoxic activities to primigravidas with an uncomplicated pregnancy. These findings support the hypothesis that maternal acceptance of the fetal-allograft is due to suppression of cell-mediated cytotoxicity. Altered cellular cytotoxicity appears unlikely as a cause of preeclampsia. Our results, however, do not preclude local changes in cellular immune activities that may occur at the implantation site.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1985

Congenital X-linked hypogammaglobulinemia and asymptomatic hepatitis B antigen carrier state.

Hepatitis occurring in patients with congenital X-linked or common variable hypogammaglobulinemia has been reported to follow a usual pattern of rapid progression from acute hepatitis to either chronic active hepatitis or death. This article describes a 21-year-old black man with congenital X-linked hypogammaglobulinemia who has been known to be a hepatitis B-associated antigen carrier during a 9-year follow up period. Liver enzyme studies are normal. His immunologic studies demonstrate no impairment of cellular immunity. His brother, who has the same disease and lives in the same household, has remained negative for hepatitis B-associated antigen. This patient demonstrates that not all hypogammaglobulinemia patients invariably have a severe clinical course with hepatitis.

Adult↗
PubMed1984

Unregulated production of virus and/or sperm specific anti-idiotypic antibodies as a cause of AIDS.

A network of idiotypic and anti-idiotypic antibodies is often suggested as the basis for cellular interactions that maintain a steady-state immunological equilibrium. This hypothesis proposes that repeated exposure to certain external antigens--ie, both viral and sperm--stimulates an unregulated production of a uniquely potent immunomodulating idiotypic antibody(ies). In a genetically predisposed individual, this particular antibody(ies), which is also an autoantibody(ies), results in a cellular immune deficiency. This disruption in the immune system permits opportunistic infection and thus the acquired immune deficiency syndrome. This hypothesis, which is readily testable and which does not involve a primary pathogen, can explain both the active induction of this disease in, as well as its passive transfer to, all at-risk populations.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Myotonic dystrophy: HLA antigens and mitogen stimulated lymphocyte responses of a black American family.

A Black American family of four generations with 29 members was studied. Six family members spanning two generations were affected with myotonic dystrophy. HLA A, B, C and DR antigen specificities were determined for each family member using local typing trays. Twelve HLA haplotypes were identified in the family. No significant association was found between the disease and any HLA antigenic type or haplotype. This finding suggests that the involvement of the major histocompatibility complex in the etiology of myotonic dystrophy is unlikely. The cellular responses to twenty-eight family members and 20 unrelated Black Americans to phytohemagglutinin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM), each in three concentrations, were tested with mononuclear cells prepared from peripheral blood. There was a significant difference in responses of the affected family members as compared to the unaffected family members and the unrelated Black Americans. The PHA and PWM responses of the unaffected family members are not significantly different from those of the unrelated Black American controls; however, the Con A responses of the unaffected family members are significantly higher than those of the control group at the lowest Con A dosage. The possible systemic defects of cytoskeletal structures of the affected family members are discussed.

Black People↗