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Biomedical subjects

P Stastny

Publications and source records attributed to P Stastny.

At least 73 records · Page 4Linked to original sources
PubMed1993

Sequences of HLA alleles associated with arthritis in adults and children.

Adult rheumatoid factor (RF) positive rheumatoid arthritis (RA) and RF positive arthritis of childhood are associated with DRB1*0401 in Caucasians, and DRB1*0405 in Orientals, and in Ashkenazi and nonAshkenazi Jews. Certain other DRB1 alleles (DRB1*0101,1001) which have a similar sequence in the 3rd hypervariable region of the 1st domain are also associated with RA, but they appear to function as weaker risk factors. The difference in the relative strength of the associations is likely to be due to structural differences in the 1st and 2nd variable regions of the first domain of these alleles. Similarities and differences in the HLA associations between North American Caucasoid patients with juvenile arthritis in Dallas, TX, USA, and in Prague, Czechoslovakia, are discussed.

Adult↗
PubMed1992

DNA typing for HLA class I alleles: I. Subsets of HLA-A2 and of -A28.

A group of HLA-A locus alleles known to be comprised of approximately 14 closely related variants are collectively called HLA-A2 and -A28. Variations among these alleles are given by differences in only a few codons, and in the case of A*6901, elements of A*6801 (exons 1 and 2) and of A*0201 are combined. The purpose of these experiments was to determine the possibility of designing oligonucleotide probes to identify and develop a typing method for all or most of the A2 and A28 variants. Because the regions of interest are also shared by alleles of other groups, allele-specific or group-specific primers were needed to amplify only the alleles under study. HLA-A2-specific amplification of exon 2 and selective amplification of portions of exon 3 of the A2-A28 group were accomplished with sequence-specific primers and after appropriate adjustments of the PCR conditions. Hybridization patterns using products of four PCR reactions with our set of probes distinguished 11 alleles. Two other alleles might be recognized with the reagents used, but were not found in the panels in this study. A*0201 and A*0209, which are different in exon 4, were not resolved because exon 4 was not tested. A new variant of Aw68, defined by a hybridization pattern obtained with our probes, was different from A*6801 only in that it was negative with probe A6. It was called A*68.3. Population studies were performed in North American whites, blacks, and Indians and in a sample of subjects from North China. HLA-A*0201 was the most frequent allele. A*0202 was found only in blacks, and A*0203 and A*0207 were found only in Chinese. Among the A28-positive subjects, Caucasoids were predominantly A*6801 or A*68.3; A*6802 was the most frequent subtype in American blacks; among American Indians the predominant type was A*68.3. The two A28-positive Chinese subjects studied had A*6901. The results obtained demonstrate that DNA typing is an efficient method for determining these alleles. The methodology should be applicable to other class I groups and should be useful for more extensive population studies, for matching for bone marrow transplantation, and for investigation of certain diseases associated with HLA class I alleles.

Alleles↗
PubMed1992

Contribution of family, cognitive and clinical dimensions to long-term outcome in schizophrenia.

A multivariate approach incorporating both biological and psychosocial factors was used in a cross-sectional study of schizophrenic inpatients and outpatients selected to represent opposite ends of the outcome spectrum. Twenty-six RDC-diagnosed chronic schizophrenic patients hospitalized continuously for 18 months or longer, and 26 patients with a history of at least three years of community tenure without rehospitalization were matched for sex, age, ethnicity, SES and chronicity, and assessed on a structured family interview (Social Behavior Assessment Schedule), neuropsychological test battery, Brief Psychiatric Rating Scale and Premorbid Asociality Scale. Stepwise discriminant function analysis was performed; family ratings of patients' problem behaviors was the most powerful discriminator between the two groups and a composite measure of neuropsychological functioning ranked second. Other significant discriminators were BPRS scores, availability of social support to the family and age of onset. Family ratings of patient behavior were related to ratings of family burden and to BPRS scores. Further research is needed to understand the complex interactions between the diverse sets of social, clinical and neurobiological factors that determine long-term outcome in schizophrenia.

Activities of Daily Living↗
PubMed1992

Gender differences in cognition in schizophrenia.

Gender differences in cognition were investigated in schizophrenic inpatients and outpatients using the Dementia Rating Scale. Females displayed greater impairment on Attention and Conceptualization than males. Gender interacted with patient group for construction: females performed worse than males among inpatients and better among outpatients. Results may be related to the atypically early age of onset of females relative to males; attention to sampling and selection biases is needed in evaluating gender differences in cognition in schizophrenia.

Adult↗
PubMed1992

Comparison of HLA class II alleles in Gypsy and Czech populations by DNA typing with oligonucleotide probes.

Czechs (CZ) and Gypsies (GY) have lived in the same country for several centuries but seem to have different migratory origins. We have studied 99 CZ and compared them with 34 GY from an isolated group living in Czechoslovakia. DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 and DPB1 alleles were determined by PCR followed by oligonucleotide hybridization. DRB1*0701 was the most frequent DR allele in CZ (af = 36.3%). In GY, after DRB1*0701, DRB1*1404 was the second most frequent allele (af = 29.4%), while in CZ this allele was not found. Both groups differed also in the distribution of DR4 subtypes. In CZ, DRB1*0401 was the most frequent subtype (50.0%) of DR4. In GY, DRB1*0408 was the predominant type (44.4%). A new DQB1 pattern was found in GY, which we have called DQB1*3.4. This allele was similar to DQB1*0301 in codon 26, but in codon 57 it resembled DQB1*0302. All cells having this new allele were also positive for DRB1*0408. Four-locus associations in CZ showed haplotypes similar to those previously found in other Caucasoid populations. In GY we observed more unusual haplotypes, some previously seen in the Orient, possibly reflecting GY ancestry.

Alleles↗
PubMed1992

Neuropsychological discriminators of long-term inpatient or outpatient status in chronic schizophrenia.

This study investigates specific neuropsychological functions discriminating schizophrenic patients with hospitalization beyond 18 months from patients residing in the community without rehospitalization beyond 3 years. Twenty-six Research Diagnostic Criteria-diagnosed chronic schizophrenic outpatients and 26 inpatients matched for sex, ethnicity, socioeconomic status, and chronicity completed a comprehensive neuropsychological battery and responded to an inventory of psychopathology. Discriminant function analyses showed that measures of motor coordination, preservation, memory, and attention discriminated between patient groups. Bilateral simultaneous fine motor coordination was the most potent discriminator between patient groups, independent of psychopathology. Implications for treatment and research on course and outcome in schizophrenia are discussed.

Activities of Daily Living↗
PubMed1991

A variant of HLA-DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews.

HLA-DR4 is associated with risk for developing rheumatoid arthritis (RA) in most populations. In Israeli Jews, in whom the Dw10 subtype of DR4 predominates, no association of RA with DR4 has been found. The inability to detect an association could be due to the high frequency of DR4-Dw10. We used DNA typing with amplification by the polymerase chain reaction and dot-blotting with allele-specific oligonucleotides to determine DR4 variants in 131 Jewish RA patients living in Israel and 134 controls. In both Ashkenazi Jews and non-Ashkenazi Jews, the rare variant Dw15 (previously identified in Japanese populations and in Japanese patients with RA) was found to be the main allele associated with the risk of developing RA (relative risk = 9.2, corrected P less than 0.001). However, this low-frequency allele could be responsible for susceptibility in only 11.5% of the patients. Susceptibility for rheumatoid factor-positive RA was associated with Dw4 and Dw15; the risk for rheumatoid factor-negative RA was associated only with Dw14. The distribution of the HLA-DQ alleles associated with DR4 showed that more than half of the RA patients with Dw15 also had HLA-DQw2. The frequencies of DQw7 and DQw8 were not different in RA patients compared with controls. The results suggest that, as in other populations, susceptibility for the development of RA in Israeli Jews is associated with DRB1 locus alleles of the DR4 group.

Alleles↗
PubMed1991

HLA-DPB1*0301 is a major risk factor for rheumatoid factor-negative adult rheumatoid arthritis.

HLA-DPB1 alleles were determined using the polymerase chain reaction and allele-specific oligonucleotide probes in Caucasoid patients with rheumatoid arthritis (RA) and in healthy controls. DPB1*0301 was found to be increased in seronegative patients (50.0% versus 10.8% in controls; relative risk = 8.3, P less than 0.0001). With our previous finding that DPB1*0301 is increased in seronegative children with polyarticular-onset arthritis, the results suggest a relationship between this disease and seronegative RA in adults.

Adult↗
PubMed1991

HLA antigens and risk for development of pemphigus foliaceus (fogo selvagem) in endemic areas of Brazil.

Endemic pemphigus foliaceus (EPF), is an autoimmune disease associated with production of IgG antibodies against epidermal antigens. We have tested 38 patients and 50 control subjects living in endemic areas to investigate whether HLA genes are associated with host factors that determine whether or not exposed individuals will develop this disease. A variant of HLA-DR1, an antigen common in Blacks (DRB1*0102), was found to be the main susceptibility factor (relative risk = 7.3, P less than 0.0002). Two amino acids, in positions 85 and 86 of DRB1, distinguish DRB1*0102 from DRB1*0101. These residues appear to be involved in the formation of a functional epitope that causes T cell recognition and determines disease susceptibility. Moreover, subjects having DQw2 did not develop the disease, while the frequency of DQw2 in controls was 22% (RR = 0.04, P less than 0.006). Thus HLA genes appear to play a crucial role in the response to an environmental factor which in this setting frequently leads to the development of autoimmune disease. An HLA-DQ allele, DQw2, appears to be associated with factors that prevent the development of the disease in exposed individuals.

Autoimmune Diseases↗
PubMed1991

DNA typing for class II HLA antigens with allele-specific or group-specific amplification. IV. Typing for alleles of the HLA-DR2 group.

In this study we present an approach for the definition of the alleles belonging to the HLA-DR2 group by DNA typing with oligonucleotide probes. Following methodology similar to that we used previously for the definition of other HLA-DR subsets, we have now developed primers for DR2-DRB1 and DR2-DRB5 amplification, and probes for the identification of sequences that distinguish the subtypes of this group of genes. The method used defines all the previously described alleles at both DR2-associated DRB loci. In addition, we have identified a variant of DRB1-DR2-Dw2. This new allele has been called DRB1*15.3. It is different from DRB1*1501 in codon 30, where it carries histidine instead of tyrosine. Eight different haplotype combinations of DRB5, DRB1, and DQB1 were identified within the DR2 group and their occurrence in four normal panels of different ethnic origin has been described. Haplotypes containing DRB1*15.3 occurred most frequently in black panel members in whom it was associated with either DQB1*0602 or DQB1*0501. Two unusual haplotypes were observed: one containing elements of DR2-Dw21 (DQB1*0502) and of DR2-Dw22 (DRB1*1602) and one containing elements of Dw21 (DRB1*1601, DQB1*0502) and Dw2 (DRB5*0101). The methods described permit simple and rapid determination of the alleles of the HLA-DR2 group and should be useful for population studies and for investigation of DR2-associated diseases.

Alleles↗
PubMed1991

DNA typing for class II HLA antigens with allele-specific or group-specific amplification. III. Typing for 24 alleles of HLA-DP.

The second exon of HLA-DPB includes five polymorphic segments with extensive sharing of sequences between alleles. In order to facilitate assignment of specificities in heterozygous individuals, we have used group-specific amplification of two nonoverlapping sets of DPB alleles (here called group A and group B) with especially designed primers. Group A and group B polymerase chain reaction products were hybridized with sequence-specific oligonucleotide probes generating easily recognizable patterns which defined 24 distinct HLA-DPB alleles. We also established a routine procedure for distinguishing HLA-DP homozygosity from failed amplification in one of the alleles. Our results showed that when only one allele was detected, failure of amplification had occurred in less than 4% of the cases. DNA typing with this method correlated well with primed-lymphocyte typing for HLA-DP in the Tenth Workshop, as determined by us in assays performed on the workshop B-cell lines. Two normal panels of unrelated subjects were tested to obtain population frequencies. We conclude that this method is simple, relatively quick, and accurate. It is the method of choice for studies to determine the role of HLA-DP alleles in T cell reactions, in various diseases, and in transplantation.

Alleles↗
PubMed1991

DNA typing for class II HLA antigens with allele-specific or group-specific amplification. V. Typing for subsets of HLA-DR1 and DR'Br'.

Three DRB1 alleles of the DR1 group including DRB1*0101, DRB1*0102, and DRB1*0103 are currently recognized. The first two of these are defined as HLA-DR1 by serologic typing and as either Dw1 or Dw20 by typing with T cells. DRB1*0103, previously called DR'Br' or DR'BON', is not detectable by serology. Little information exists about the population frequencies of DRB1*0102 and DRB1*0103. In the present study we have used the polymerase chain reaction (PCR) and allele-specific oligonucleotide probes to determine these alleles. To avoid cross-hybridization with other DRB genes having the same DNA sequences as those of the region to be analyzed, we performed group-specific PCR to amplify only DR1 DRB1 genes. This was accomplished using a 21-nucleotide-long primer, homologous to the first hypervariable region common to the DR1 DRB1 genes, and which under appropriate conditions amplified only DRB1 genes of the DR1 group. Five oligonucleotide probes, one matching the second hypervariable region, two spanning the third hypervariable region, and two covering codons 82 through 89, were used to determine the three alleles. DRB1*0101 (Dw1) was found to be the major type of DR1 in North American Caucasians. In North American black and Brazilian mestizo populations DRB1*0102 (Dw20) was more prevalent. DRB1*0103 (DR'Br') was detected in only six individuals in the present study.

Alleles↗
PubMed1991

Alloantibodies against donor epidermis and early kidney transplant rejection.

We have previously observed that transplant recipient sera with endothelial antibodies are bound to epidermal cells, as shown by immunofluorescence on sections of skin. It was also reported that early kidney failures that occurred despite negative T cell crossmatches were associated with, and could have been predicted by, a crossmatch with donor skin. Ninety patients undergoing kidney transplantation have now been evaluated using this technique. A few other patients were excluded from the analysis because of the presence of autoantibodies staining autologous skin. In 12 the crossmatch with donor skin was positive, and 9 of them had severe rejection within the first 10 days after transplantation. The three patients with a positive skin crossmatch and a benign course had not been tested with autologous skin and therefore autoantibodies could not be excluded. Only 7 of the 78 patients with negative skin crossmatches had early rejection. The correlation between skin crossmatch and early rejection was statistically highly significant (P less than 0.0001). Studies by flow cytometry have shown that these antigens are found on the surface of epidermal and endothelial cells, and are modulated by gamma interferon. When tested against a panel of skin donors, skin alloantibodies gave different patterns of positive and negative reactions, suggesting polymorphism.

Antigens, Surface↗