SEARCH · PubMed Health

Results for “Reference panel”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

PubMed1975

Hepatitis B antigen, antigen subtypes, and hepatitis B antibody in normal subjects and patients with liver disease.

The relative sensitivities of counterimmunoelectrophoresis (CIE) and haemagglutination assays for the detection of hepatitis B surface antigen (HB(s)Ag) and antibodies (anti-HB(s)) were compared. Twelve scientists from ten countries in Asia, Africa and the Pacific region participated in the study. The participants provided serum samples from 15 953 subjects comprising patients with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), as well as blood donors and other normal individuals. For the detection of HB(s)Ag in a reference panel serum, immune adherence haemagglutination (IAHA) was slightly more sensitive than passive haemagglutination inhibition (PHI); CIE was the least sensitive. Mean HB(s)Ag frequencies in patients with acute hepatitis, chronic hepatitis, cirrhosis, and HCC were significantly higher than in healthy controls. Passive haemagglutination (PHA) was more sensitive than CIE for the detection of anti-HB(s). The frequency of anti-HB(s) in patients with HCC was significantly lower than that in the other groups. Mean anti-HB(s) frequencies in patients with acute hepatitis, chronic hepatitis, and cirrhosis were not significantly different from that in normal subjects. Subtyping of HB(s)Ag was performed by PHI. Among asymptomatic carriers the predominant HB(s)Ag subtype in northeast Asia was adr.In India, ayw predominated in carriers, with the demarcation between adr and ayw occurring west of Burma. In West Africa the only subtype detected was ayw, but in East Africa the majority subtype was adw. The r subtype was found only in Asian populations east of India and in Western Pacific populations. In Papua New Guinea all four subtypes were identified. With one possible exception, the subtypes of HB(s)Ag-positive patients with liver disease reflected the predominant type in each geographic location.

Africa↗

PubMed2001

Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors.

Length alterations in microsatellite repeats, termed microsatellite instability (MSI), are found in 10-15% of sporadic colon, endometrial, and gastric cancers harboring defects in DNA mismatch repair (MMR) genes We used the microsatellite markers Big Adenine Tract (BAT) 26 and BAT-25 from the reference panel of five markers recommended by the National Cancer Institute to evaluate the incidence of MSI in 206 central nervous system tumors. We screened 102 pediatric and 104 adult cases representing 165 astrocytic and 41 nonastrocytic tumors. The overall incidence of MSI was 8% (16 of 206). All 16 tumors with MSI were found in pediatric rather than adult patients. MSI was associated with two distinct subtypes of pediatric tumors occurring in 27% (12 of 45) of WHO grade III and grade IV astrocytomas and 24% (4 of 17) of gangliogliomas We evaluated the difference in clinicopathological and genetic features among 45 high-grade pediatric astrocytomas by MSI status. The median survival for pediatric patients with MSI (n = 12) was 8 months compared with 15 months for those patients without MSI (n = 33; P = 0.18). The frequency of p53 gene mutations was 13% for pediatric patients with MSI (n = 8) compared with 47% for those patients without MSI (n = 19; P = 0.19). These results revealed a trend between MSI status and prog nosis and MSI status and frequency of p53 gene mutations. Our data suggest that pediatric high-grade astrocytomas can be attributed to two different genetic pathways: a MMR-deficient pathway and a MMR proficient pathway.

Adolescent↗

PubMed2001

In situ identification and analysis of automotive paint pigments using line segment excitation Raman spectroscopy: I. Inorganic topcoat pigments.

Several applications of Raman spectroscopy in the forensic sciences have recently been demonstrated, but few have involved the analysis of paints. Undoubtedly, this is a reflection of the sample degradation problems often encountered when a visible or near-infrared laser is focused on a light-absorbing matrix. In this study, a dispersive CCD Raman spectrometer (785 nm) was used in a configuration which collected scattered light from an excitation region 3 mm long and 80 microm wide, instead of from a focused spot. Sample degradation was not observed, and Raman spectra of automotive paints of all colors were readily obtained. Most of the paints analyzed were U.S. automobile original finishes (1974 to 1989) from the Reference Collection of Automotive Paints, and the inorganic pigments examined were those which had been identified previously by infrared spectroscopy in finishes from this collection. Prominent peaks of rutile were observed in Raman spectra of light-colored nonmetallic finishes for both monocoats and basecoat/clearcoat systems, and the rutile peaks are readily distinguished from those of anatase. The lead chromates (Chrome Yellow, Molybdate Orange, and silica-encapsulated versions of the two) are the strongest Raman scatterers among the pigments examined, and Chrome Yellow was identified by Raman spectroscopy in several yellow and orange nonmetallic monocoats for which infrared absorptions of this pigment were not observed. Raman spectroscopy also provides an unequivocal means to distinguish Chrome Yellow from Molybdate Orange. This is particularly helpful for the analysis of paints containing light pigment loads or encapsulated pigments since the two formulations cannot be differentiated by infrared spectroscopy in such cases. The iron-containing pigments, ferric oxide, hydrous ferric oxide, and Prussian Blue, are relatively weak Raman scatterers, but peaks of hydrous ferric oxide and Prussian Blue were observed in spectra of paints containing heavy pigment loads. Because no sample preparation is required. Raman spectroscopy provides an excellent means to rapidly screen reference panels for the presence of certain pigments, and some examples of the differences in Raman spectra which occur for paints having similar colors are presented.

Journal Article↗

PubMed2001

Requirements for testing human blood donors for evidence of infection due to communicable disease agents. Final rule.

The Food and Drug Administration (FDA) is revising the general biological product standards applicable to human blood and blood components by updating the hepatitis B virus (HBV) and human immunodeficiency virus (HIV) testing requirements, by adding testing requirements for hepatitis C virus (HCV), human T-lymphotropic virus (HTLV), and by adding requirements for supplemental (i.e., additional, more specific) testing approved for such use by FDA when a donation is found to be reactive for any of the required screening tests for evidence of infection due to communicable disease agents. The agency also is requiring manufacturers of certain test kits to use reference panels, when available, to verify the acceptable sensitivity and specificity of each lot. This final rule is intended to help protect the safety and ensure the quality of the Nation's blood supply, to enhance the safety of medical devices containing blood or blood components, to provide FDA with clear enforcement authority, and to promote consistency in the industry. Elsewhere in this issue of the Federal Register, FDA is publishing a rule requiring blood and plasma establishments to notify donors, including autologous donors, whenever the donor is deferred or determined not to be suitable for current or future donations of blood and blood components.

Biological Products↗

PubMed1975

Specific detection of hepatitis B surface antigen utilizing chimpanzee and guinea pig antibodies in a solid-phase radio-immunoassay.

The test involves a primary incubation of sample in polystyrene tubes coated with avid guinea pig anti-HBs serum followed, after washing, by a secondary incubation with immunopurified I125 chimpanzee anti-HBs. The system was found to be suitable for automation of washing and counting. The Hebria kit eradicated the non-specific positives obtained in those tests employing antibody from only one animal species and had third generation sensitivity (35 positives out of 50 samples) with the U.S. hepatitis B reference panel No. 2. Dilution analysis of both antigen subtypes showed that Hebria was as sensitive as Ausria II. By absorbing monospecific guinea pig antisera prior to coating, the kit showed greater than 10-fold discrimination between the ad and ay antigen subtypes while retaining high sensitivity. The kit could also quantitate and subtype anti-HBs in plasma samples.

Animals↗

PubMed2002

Genetic classification of colorectal cancer based on chromosomal loss and microsatellite instability predicts survival.

PURPOSE: Colorectal cancers harbor one of two distinct alterations, unilateral chromosomal loss as evidenced by a loss of heterozygosity (LOH) and microsatellite instability (MSI), as represented by the widespread insertion or deletion of simple repeat nucleotides. We investigated the relationships between the clinicopathological features and microsatellite alterations (LOH and MSI) of 168 colorectal cancers. EXPERIMENTAL DESIGN: The concerted and individual effects of various chromosomal losses on survival were comparatively analyzed using a reference panel of 40 microsatellite markers in eight cancer-related chromosomes, 3p, 4p, 5q, 8p, 9p, 13q, 17p, and 18q. RESULTS: Of the 168 colorectal cancers tested, 29 (17%) with high-frequency MSI were associated with good survival (P < 0.05). The extent of LOH detected in 139 (83%) cases without MSI was classified as low level involving three or fewer arms (35%), moderate level involving four arms (22%), or high level involving five or more arms (43%). High-level loss correlated with earlier onset, lymphatic invasion, and rectal location, whereas low-level loss was more common in proximal colon and stages I and II (P < 0.05). The survival curve and multivariate analysis identified high- and low-level chromosomal loss as the most significant predictor of poor and good survival, respectively (log-rank test, P < 0.0001), in patients with stage II (hazard ratio, 6.27; 95% confidence interval, 1.99-19.7; P = 0.0017) and those with stage III (hazard ratio, 10.89; 95% confidence interval, 2.54-46.77; P = 0.0013). Moderate chromosomal loss showed dual prognostic values associated with favorable stage II and unfavorable stage III. Single chromosomal losses tended to play a role as a part of the concerted chromosomal function. CONCLUSION: The classification of colorectal cancer based on chromosomal loss and MSI provides a prognostic index that reflects tumor pathobiology.

Alleles↗

PubMed2002

Frequent microsatellite instability in sporadic tumors of the upper urinary tract.

Urothelial carcinoma of the renal pelvis and ureter may develop sporadically or as a manifestation of hereditary nonpolyposis colorectal cancer. The majority of hereditary nonpolyposis colorectal cancer is caused by mutation of the human DNA mismatch repair (MMR) genes and is detected by associated microsatellite instability (MSI). Seventy-three unselected urothelial carcinomas of the ureter and/or renal pelvis were screened for MSI using the National Cancer Institute-designated reference panel (plus BAT40). Instability of at least two microsatellite markers (MSI-high) was detected in 15 samples (21%). Immunohistochemical staining of the MMR proteins (hMSH2, hMLH1, or hMSH6) was absent in 13 of 15 (87%) MSI tumors, and alteration of coding sequence microsatellites (TGFbetaRII, Bax, hMSH3, and hMSH6) was found at frequencies of 7-33% in these samples. Tumors with MSI had significantly different clinical and histopathological features including higher prevalence in female patients, low tumor stage and grade, and a papillary and frequently inverted growth pattern. Our results suggest a molecular pathway of tumorigenesis that is similar to MMR-deficient colorectal cancers and consistent with the notion that the site distributions of hereditary or sporadic MSI-high tumors may reflect tissue-specific susceptibility to lesions processed by the MMR machinery.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Alterations of the K-ras and p53 genes and microsatellite instability in sporadic colorectal carcinomas.

BACKGROUND: The international guidelines for the evaluation of microsatellite instability (MSI) in colorectal cancer were defined in 1997 by the National Cancer Institute (NCI). Here, the relationship between MSI, cancer-associated genes and their clinicopathological variables were revaluated using these guidelines. PATIENTS AND METHODS: Mutations of K-ras at exon 1 and p53 at exons 5, 6, 7 and 8 were analyzed in 43 cases of sporadic colorectal carcinoma. MSI was analyzed using the 5 markers recommended by the NCI reference panel. RESULTS: The proportion of p53 mutations in the MSI-H cases (0 out of 5; 0%) was lower than that of non-MSI-H cases (23 out of 38; 60.5%) (p=0.0117). The proportion of p53 mutations in microsatellite stable (MSS) cases (21 out of 34; 61.8%) was higher than that of non-MSS cases (2 out of 9; 22.2%) (p=0.0366). The proportion of K-ras mutations in MSI-H tumors (1 out of 5; 20.0%) was less frequent than in non-MSI-H tumors (19 out of 38; 50.0%) (p=0.2115). CONCLUSION: p53 mutations in MSI-H tumors were much less common than in non-MSI-H tumors. This result suggested that alterations of the p53 gene are not closely associated with carcinogenesis in MSI-H carcinomas.

Aged↗

PubMedDate not supplied

[Dynamics of humoral immune response to Treponema pallidum proteins p17 and p41 at early stages of syphilis].

In 60 blood sera from syphilis patients the titers of IgG to T. pallidum antigens p17 and p41 were detected with the use of the test system based on the recombinant analogues of T. pallidum proteins. The study revealed that primary syphilis was characterized by considerable prevalence of IgG to protein p41 with the total antibody level being low, while early latent syphilis was characterized mainly by considerable prevalence of IgG to protein p17 in the presence of high titers of antibodies. In secondary syphilis the sera contained a high total antibody level and a wide range of IgG ratios to individual antigens. On the basis of the data obtained the dynamics of immune response to antigens p17 and p41 at the early stages of the disease was hypothetically plotted. The curves of antibody levels had a wave-like character with the phase shifts of peaks for individual proteins and very low antibody titers (less than 1:100) in the negative peak areas. Conclusions were made that it was necessary to use the mixture of antigens in the production of the test systems and, when designing reference panels of sera, to include sera with extremely low titers of antibodies to individual proteins.

Antibodies, Bacterial↗

PubMed1997

A modified PCR-RFLP genotyping method demonstrates the presence of the HPA-4b platelet alloantigen in a North American Indian population.

The diallelic HPA-4 (Pen/Yuk) platelet alloantigen system is polymorphic in Asian populations and accounts for the majority of cases of neonatal alloimmune thrombocytopenia in Japan. At the molecular level, the HPA-4a/4b dimorphism is associated with an arginine/ glutamine substitution at amino acid 143 of the gene encoding platelet glycoprotein IIIa. Unlike the five other major diallelic human platelet antigen systems (HPA-1, -2, -3, -5, and -6), the nucleotide substitution corresponding to the HPA-4 antigen system does not involve a common naturally occurring restriction enzyme site. This paper describes a new genotyping method for HPA-4 (polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]) that involves restriction enzyme digestion of PCR-amplified genomic DNA using a modified PCR primer to create an artificial TaqI restriction site that is present in the HPA-4a but not in the HPA-4b DNA sequence. The HPA-4 PCR-RFLP method was validated by testing a reference panel of 10 known HPA-4 genotyped Japanese individuals. Thus, genotyping by PCR-RFLP can now be performed for all six major HPA systems. Using the HPA-4 PCR-RFLP genotyping method, we determined a frequency of 2.9 percent for the HPA-4b allele in a North American Indian population. This finding indicates the importance of the HPA-4 antigen system as a potential cause of alloimmune thrombocytopenia in American Indians.

Journal Article↗

PubMed1992

Autosomal dominant retinitis pigmentosa (adRP; RP6): cosegregation of RP6 and the peripherin-RDS locus in a late-onset family of Irish origin.

We recently reported the localization of a gene for late-onset autosomal dominant retinitis pigmentosa (adRP; RP6), on the short arm of chromosome 6, by linkage analysis in a large family of Irish origin. It is notable that the gene encoding peripherin-RDS, a photoreceptor-specific protein, recently has been physically mapped on 6p. In our own analysis, an intrageneic marker derived from this gene cosegregated with the adRP disease locus with zero recombination (lod score 5.46 at q = .00). Using the CEPH reference panel, we now report the mapping of the peripherin-RDS gene relative to other 6p markers in the CEPH data base. Incorporation of these data into a multipoint analysis produced a lod score for adRP of 8.21, maximizing at the peripherin-RDS locus. This study provides strong evidence suggesting a role for peripherin-RDS in the etiology of one form of adRP.

Base Sequence↗

PubMed2005

Detection of occult high graded microsatellite instabilities in MMR gene mutation negative HNPCC tumors by addition of complementary marker analysis.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant tumor syndrome predisposing to predominantly colorectal and endometrial cancer. In 90% of the cases, molecular analyses reveal microsatellite instabilities due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2, among these tumors. PATIENTS AND METHODS: Tumors from 40 HNPCC index patients (31 Amsterdam positive, 9 Bethesda positive; 21 females, 19 males; mean age 48.0 +/- 13.2 years) were examined. In contrast to the classical constellation, their tumors revealed only a microsatellite stable (MSS, n=31)--or low instable (MSI-L, n=9)--tumor phenotype following the international reference panel of 5 microsatellites. No MLH1 and MSH2 mutations were detectable. Complementary microsatellites (BAT40, D10S197, D13S153, D18S58, MYCL1) were investigated by PCR and fragment analysis to find other instabilities which might hint to the MIN-pathway of the tumors. RESULTS: Due to ten microsatellites in total tumors were now reclassified in 4 MSI-H (10%), 24 MSI-L (60%) and 12 in MSS (30%) phenotypes. The mean age of onset for CRCs was the lowest in the MSI-H group with 45.7 +/- 9.6 years (vs. 48.7 +/- 14.3 and 49.0 +/- 12.9 years in MSI-L and MSS group). MSI-H-and MSI-L tumors were often localized in the proximal colon (50 and 52%), whereas MSS tumors were preferentially localized in the distal colon (77%). - CONCLUSION: Complementary microsatellites help to subdive "non-classical" HNPCC in subgroups with different clinical appearance. It allows to detect occult MSI-H tumors with up to 10% and to confirm MSS tumors who seem to have a similar biological behaviour like sporadic CRC. Maybe that this genetic reclassification influence the decision of whether to offer patients chemotherapy or not, since it is known that patients with instable tumors do not benefit from chemotherapy as well as patients with microsatellite stable tumors.

Base Pair Mismatch↗

PubMedDate not supplied

A new method for optimizing multiplex DNA microsatellite analysis in low quality archival specimens.

BACKGROUND: Testing microsatellite instability seems to be a useful tool for the initial screening of putative non-polyposis colorectal cancer (HNPCC), preceding analysis of germ-line mutations of DNA mismatch repair genes. However, diagnosis of microsatellite instability becomes complicated when highly-damaged DNA from formalin-fixed paraffin-embedded tissue specimens has to be investigated. MATERIALS AND METHODS: A new methodical approach was established based on special multiplex PCR regimes (e.g., on touch-up cycling conditions), allowing both sufficient, as well as specific, amplification of the Bethesda reference panel loci with low quality DNA as template. RESULTS: By applying our new method, microsatellite instability could be analyzed successfully in 75 out of 84 investigated tumors (89%), whereas, by using standard PCR protocols, microsatellite analysis failed in 36% of the investigated cases. CONCLUSION: Our new methodical approach should be recommended for the use of archival material since it allows an efficient and accurate amplification of the Bethesda marker fragments and is less dependent on the DNA quality.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Relation of HLA antibodies and graft atherosclerosis in human cardiac allograft recipients.

Although cyclosporine has helped make heart transplantation a clinical reality, long-term survival remains limited by rejection and graft atherosclerosis. We have previously demonstrated the development of alloreactive lymphocytotoxic antibodies in baboon recipients of heterotopic heart transplants despite cyclosporine administration. The hypothesis of the present study is that cyclosporine-treated human heart transplant recipients are also capable of generating strong humoral immune responses that might adversely affect clinical outcome. Serial serum specimens from 240 heart transplant recipients were tested against a reference panel of 70 cells for anti-HLA lymphocytotoxic antibodies. Patients with serum panel reactive antibody levels greater than 10% were considered antibody producers, whereas those with serum panel reactive antibody levels less than 10% were considered nonproducers. To establish the time course of post-transplantation sensitization, we have tested anti-HLA antibodies in sequential sera at 3-month intervals after transplantation. The 4-year actuarial survival rate of those patients whose panel reactive antibody levels were greater than 10% during the first 6 months after transplantation was 70%, whereas the survival rate of patients whose levels were less than 10% during this time was 93%. The results were significantly different (p less than 0.01). Further heterogeneity among the patients was demonstrated by differential analysis of survival in patients who showed (1) panel reactive antibody levels less than 10% in any of the sera obtained during the first year after transplantation, (2) panel reactive antibody levels greater than 10% in sera obtained during the first 6 months but not thereafter, and (3) panel reactive antibody levels greater than 10% throughout the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2006

Clinical performance of the new rRoche COBAS TaqMan HCV Test and High Pure System for extraction, detection and quantitation of HCV RNA in plasma and serum.

We evaluated the Roche COBAS TaqMan HCV Test For Use With The High Pure System (TaqMan HPS; Roche Diagnostics), for the extraction, detection and quantitation of hepatitis C virus (HCV) RNA in serum or plasma of HCV-infected individuals. The TaqMan HPS is a real-time PCR assay with a reported linear dynamic range of 3.0x10(1) to 2.0x10(8) HCV RNA IU/ml, and a reported lower limit of detection (LLD) of 10 IU/ml. Calculation of the HCV RNA titre is based upon an external standard curve in the presence of an internal control. Intra-assay and inter-assay variation were small in reference panel members with HCV RNA > or =100 IU/ml. Genotype performance and quantitative correlation between the TaqMan HPS and the bDNA (VERSANT HCV 3.0 assay; Bayer Diagnostics), assessed in 59 patient samples, were good for HCV genotype 1 but poor for genotypes 2, 3 and 4. For genotypes 2, 3 and 4, values obtained from the TaqMan HPS were in general 0.5 log lower than those from the bDNA. Sensitivity was poor in low viral titre samples of genotypes 1, 2, 3 and 4. The LLD (95%) was estimated at 41 HCV RNA IU/ml for genotype 4. The TaqMan HPS underestimates HCV RNA at all levels in plasma and serum from HCV-infected individuals, and the LLD should be reconsidered. This is clinically relevant because underestimation of HCV RNA levels during therapy may lead physicians into making incorrect treatment decisions.

Branched DNA Signal Amplification Assay↗

PubMed1991

A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates.

Utilizing the CEPH reference panel and genotypic data for 53 markers, we have constructed a 20-locus multipoint genetic map of human chromosome 4. New RFLPs are reported for four loci. The map integrates a high-resolution genetic map of 4p16 into a continuous map extending to 4q31 and an unlinked cluster of three loci at 4q35. The 20 linked markers form a continuous linkage group of 152 cM in males and 202 cM in females. Likely genetic locations are provided for 25 polymorphic anonymous sequences and 28 gene-specific RFLPs. The map was constructed employing the LINKAGE and CRIMAP computational methodologies to build the multipoint map via a stepwise algorithm. A detailed 10-point map of the 4p16 region constructed from the CEPH panel provides evidence for heterogeneity in the linkage maps constructed from families segregating for Huntington disease (HD). It additionally provides evidence for position-specific recombination frequencies in the telomeric region of 4p.

Chromosome Mapping↗

PubMed1990

Typing for HLA DQ using oligonucleotidic probes.

We have typed 25 homozygous B lymphoblastoid cell lines, defined as reference panel during the Xth International Histocompatibility Workshop, using PCR (Polymerase Chain Reaction) and oligonucleotidic probes recognizing sequences of DQA and DQB genes. The polymorphism of 8 HLA-DQA1, and 12 DQB1 alleles is reported and the advantages of this technique are compared to that of other typing methods, currently used.

Cell Line↗

PubMed1989

Humoral immune responses after cardiac transplantation: correlation with fatal rejection and graft atherosclerosis.

Although the advent of cyclosporine has allowed dramatic improvement in survival rates after heart transplantation, long-term outcome remains limited by rejection and graft atherosclerosis. We have previously demonstrated the development of alloreactive lymphocytotoxic antibodies in baboon recipients of heterotopic cardiac transplants despite cyclosporine administration. The hypothesis of our study is that human heart transplant recipients given treatment with cyclosporine are also capable of generating strong humoral immune responses that might adversely affect clinical outcome. Serial serum specimens from 118 heart transplant recipients were tested against a reference panel of 70 cells for anti-HLA lymphocytotoxic antibodies. Patients with positive sera on at least three separate samplings at minimal intervals of 1 week were considered to be antibody producers (Ab+), and those with less than three positive sera samplings were considered nonproducers (Ab-). Donor lymphocytes were not available for most recipients for the assessment of the specificity of antibodies produced. Seventy-six of 118 patients (64%) were Ab+. One-year, 3-year, and 5-year actuarial survival rates were 81%, 70%, and 53%, respectively, for Ab+ patients compared with corresponding rates of 93%, 90%, and 90%, respectively, in Ab- patients (p less than 0.01). Graft atherosclerosis confirmed by coronary angiography or autopsy developed in 12 Ab+ patients (16%), compared with 1 of 42 Ab- patients (2.3%) (p less than 0.05). These data show that almost two thirds of heart transplant recipients produce anti-HLA antibodies after grafting that correlate strongly with adverse outcome. Immunotherapies directed at control of deleterious humoral immune responses need to be developed.

Actuarial Analysis↗