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Biomedical subjects

P H Kay

Publications and source records attributed to P H Kay.

At least 73 records · Page 4Linked to original sources
PubMed1989

The pathophysiology of atypical tamponade in infants undergoing cardiac surgery.

A small solid state transducer was used to measure pericardial pressure (PP) in 13 pediatric patients (mean age 18 months) at hourly intervals for 24 h following cardiac surgery. The mean PP following closed cardiac surgery via a left thoracotomy (group 1: 5 patients) was 2.7 +/- 1.4 mmHg and did not change with time. Maximum PP occurred during isovolumic relaxation of the ventricle rising to a peak at the onset of the 'a' wave of the central venous pressure (CVP). PP was strongly correlated with CVP (r = 0.58, P less than 0.001) but not with airways pressure (r = 0.27, P less than 0.2). Mean PP in the 3 patients undergoing transatrial surgery (group 2) was 4.5 +/- 2.7 mmHg (group 1 vs group 2, P less than 0.001). PP was significantly raised in the 2 patients undergoing transventricular correction of Fallot's tetralogy (group 3, PP = 10.2 +/- 3.2 mmHg; group 3 vs group 2, P less than 0.001) and in the 3 patients undergoing homograft conduit reconstruction of the right ventricular outflow tract for truncus arteriosus (group 4, PP = 9.3 +/- 2.6 mmHg; group 4 vs group 2, P less than 0.001). The results confirm that PP is a mathematical function of the expansile forces of the heart and the restricting forces of the pericardium and mediastinum. Patients with pulmonary regurgitation or pulmonary hypertensive crisis leading to increased right ventricular end diastolic dimension or a space occupying conduit have a high PP and are therefore at risk of atypical tamponade. In this situation splinting open the chest may reduce PP and break the cycle of falling cardiac output.

Cardiac Tamponade↗
PubMed1988

Extensive deletions and insertions in different MHC supratypes detected by pusled field gel electrophoresis.

The genomic organization of the human MHC was examined in multiple examples of six different supratypes using pulsed field electrophoresis (PFGE) after digestion of genomic DNA with infrequency cutting restriction endonucleases. Differences in restriction fragment length and band intensity were shown to be specific for each supratype. Mapping of the MHC revealed that each supratype contains previously undescribed deletions and insertions between HLA B and DQ regions.

Chromosome Deletion↗
PubMed1988

Influence of C4 null genes on infection with human immunodeficiency virus.

The hypothesis that complement is important in the host response to human immunodeficiency virus (HIV) was tested. Complement C4 and Bf allotypes were determined in 26 patients who fulfilled the diagnostic criteria for persistent generalised lymphadenopathy due to HIV, 72 homosexuals who were negative for antibody to HIV, and 185 control subjects drawn from the local population. HLA-A, B, and DR were also typed and the phenotypes examined for the presence of supratypes and C4BQ0. Eleven patients (42%) had C4B null alleles compared with only 13 (18%) homosexuals who were negative for antibody and 28 (15%) controls. From estimates of gene frequencies the difference between the patients with lymphadenopathy and the controls was significant after conservative correction. In the patients only a minority (six) of the C4B null alleles were contained within ancestral haplotypes. Together with the fact that C4 null alleles result in partial deficiency of C4, this finding suggests that products of complement genes are important in infection with HIV or its consequences, or both. A role is proposed for complement and Fc receptors.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Class III gene rearrangements in Thai/Chinese supratypes containing null or defective C4 alleles.

Class III gene rearrangements have been examined in Thai/Chinese individuals with supratypes bearing defective or null C4 alleles. Genomic DNA from C4 null supratypes was probed with an almost full-length 21-OH probe following digestion with Taq I and Kpn I. The HLA-B17 C4A3 BQ0 BfS DR3 Thai/Chinese supratypes (which may be associated with insulin-dependent diabetes mellitus in Orientals) lacks a 3.2 kb Taq I and a 3.9 kb Kpn I fragment hybridizing with the 21-OH probe. Similar gene rearrangements are found in Caucasoid diabetogenic supratypes HLA-B18 C4A3 BQ0 BfF1 DR3 and HLA-B8 C4AQ0 B1 BfS DR3. Interethnic comparisons suggest that class II and class III interactions may be important in disease susceptibility. By contrast, neither of two Thai/Chinese supratypes with C4AQ0 appear to have major class III gene rearrangements; disease association studies will determine the significance of C4 deficiency per se. As in Caucasoids, the electrophoretically fast C4 allele, C4A6, in Orientals has been shown to correlate with a 12 kb Bgl II fragment hybridizing with a C4 probe. It is likely that the HLA-B17 C4A6 B1 BfS DR7 supratype marks a highly conserved MHC chromosomal segment.

Alleles↗
PubMed1988

Coexistence of an MHC chromosomal segment marked by HLA B17,BfS,C4A6,B1,DR7, and DQw9 in different ethnic groups.

Previously we have shown that the supratype HLA B17 BfS C4A6 B1 DR7 (17 6 1 7) carrying a C4/Bgl II RFLP correlating with C4A6 coexists in whites and Thai/Chinese. Using conventional and PFGE/Southern blotting with class II, class III, and TNF probes as well as serologic DQ subtyping, we have extended these comparisons and now report that four examples each of white and Oriental 17 6 1 7 bear DQw9, as well as an approximately 10kb fragment hybridizing with a DR beta probe following digestion of genomic DNA with Hind III. Furthermore, Oriental and white 17 6 1 7 share a genomic insertion of some 70kb close to the class II region. These data suggest that 17 6 1 7 may mark a highly conserved chromosomal segment which provides new insights into the biology and evolution of the major histocompatibility complex.

Asian People↗
PubMed1988

C4 allotyping on plasma or serum: application to routine laboratories.

Allotypes of the fourth component of complement (C4) can be detected by electrophoresis and immunofixation after treatment of EDTA plasma with neuraminidase (NAse). We have assessed the value of additional treatment with carboxypeptidase B (CPseB). Following treatment with CPseB + NAse, each allele is resolved into a single band, permitting clear definition of overlapping bands seen following treatment with NAse alone. More importantly, C4 allotypes can be determined using stored heparinized plasma or serum. Most C4 null alleles can be assigned without requiring family studies. The approach described is suitable for routine use by tissue typing laboratories.

Alleles↗
PubMed1988

HLA, C4, Bf, Gm and autoantibodies in rheumatoid arthritis.

Sera from 48 subjects with rheumatoid arthritis (RA), more than 80% of which were seropositive, were examined for the presence of antibodies to intact nuclei (ANA) by immunofluorescence, extractable nuclear antigens (ENA), double-stranded DNA by immunoassay and immunoglobulins, i.e. rheumatoid factors (RF) by haemagglutination. The genetic markers of HLA, the fourth complement component (C4) and properdin factor (Bf), which are all coded for within the major histocompatibility complex and Gm immunoglobulin allotypic markers were all analysed in relation to various parameters of these autoantibodies. The only significant association to emerge was between low ENA antibody affinities and the Bf Fs phenotype (p less than 0.02). Although weak associations between individual autoantibody parameters and the other immunogenetic markers were detected, there were no significant HLA, C4 or Gm association with either ANA subsets or RF, a finding which agrees with, and also extends previous HLA studies of predominantly seropositive RA cohorts.

Adolescent↗
PubMed1987

Polymorphism of the acetylcholine receptor in the horse.

A cDNA probe to the alpha subunit of the murine acetylcholine receptor was used to demonstrate restriction fragment length polymorphism in an acetylcholine receptor gene in the horse. Three different patterns of polymorphism have been observed with fragment sizes of 4.3 and 2.9 kilobases (kb) (pattern 1), 4.3 and 2.5 kb (pattern 2) and 4.3, 2.9 and 2.5 kb (pattern 1,2). Analysis of a three generation pedigree has suggested that patterns 1 and 2 represent two allelic forms of the gene encoding the alpha subunit of the acetylcholine receptor. These data provide a basis for the examination of the genetic control of neuromuscular function in the horse.

Alleles↗
PubMed1987

A multidisciplinary approach to primary nonseminomatous germ cell tumors of the mediastinum.

The introduction of cis-platinum-based chemotherapy has dramatically improved the prognosis for patients with primary nonseminomatous germ cell tumors of the mediastinum. Since 1978, 12 male patients (mean age, 29 years) have been seen with a large mediastinal mass, normal testes, and abnormal testicular tumor markers. Eleven patients had raised alpha-fetoprotein levels (median, 1,300 micrograms/L; normal, less than 10 micrograms/L), and 3 had elevated levels of the beta fraction of human chorionic gonadotropin (median, 8,000 IU/L; normal, less than 5 IU/L). Two patients were treated by primary surgical intervention followed by chemotherapy. Ten patients were treated with primary chemotherapy (cis-platinum, vinblastine sulfate or etoposide, and bleomycin sulfate), and this was followed by timed surgical excision of the tumor mass in 7. Six (60%) patients responded to primary chemotherapy with normalization of tumor markers. In this group there was 1 postoperative death and 1 recurrence. The 4 remaining patients are alive and free from disease at a mean of five years. Of the 4 patients with persistently elevated tumor markers, 2 died within six months, 1 is alive with recurrence, and 1 is lost to follow-up at three months. Patients whose tumor markers return to normal after cis-platinum-based chemotherapy have a good long-term prognosis following radical surgery. If the tumor markers remain elevated, the prognosis is poor.

Adult↗
PubMed1987

MHC supratypes as markers of null and defective C4 alleles in a Thai/Chinese population: relevance to disease susceptibility.

Deficiency alleles at the C4 loci within the MHC are associated with autoimmune diseases in Caucasoids and possibly other races. We therefore studied the relationship between relevant C4 alleles and other MHC markers in a random Thai/Chinese population. Over 90 per cent of C4AQO occurs within two supratypes (HLA Aw33, B44, C4AQO, B1, BfS, DR7 and Aw33, B17, C4AQO, B1, BfF DR x where x is an unassigned DR antigen). These two supratypes have minimum population frequencies of 6 and 3 per cent, respectively. Almost 70 per cent of C4BQO is contained within the supratype HLA Aw33 (11), B17, C4A3, BQO, BfS, DR3. At least 8 per cent of the Thai/Chinese population bear this supratype. Essentially all subjects with C4A6 also have HLA A1, B17, C4B1, BfS, and DR7. Approximately 6 per cent of Thai/Chinese have this supratype which is also found in Caucasoids. Partial C4 deficiency is common in Thai/Chinese as well as Caucasoids, can be inferred from examination of HLA phenotypes and may contribute to susceptibility to some diseases.

Alleles↗
PubMed1986

Electrophoretic polymorphism and molecular structure of equine C3.

Plasma or serum samples from 12 Arabian and 181 standardbred horses have been typed using an immunofixation technique to determine electrophoretic polymorphism of equine third complement component (C3). Six distinctly different electrophoretic patterns of equine C3 have been recognized thus far. SDS PAGE analysis of equine C3/anti C3 complexes revealed that the submolecular structure comprised an alpha chain and beta chain of molecular weights approximately 118,000 and 63,000 daltons respectively. The molecular weights of the alpha and beta chains were similar in all electrophoretic variants tested. Family data derived from 73 mares, 21 stallions and 99 offspring suggested that the six electrophoretic phenotypes were inherited by means of three codominant alleles named C3-1, C3-2 and C3-3 at a single autosomal locus.

Animals↗
PubMed1986

Genetic studies in familial fibrosing alveolitis. Possible linkage with immunoglobulin allotypes (Gm).

A family containing 12 subjects spanning three generations and including six cases with clinical evidence of definite or probable fibrosing alveolitis has been investigated. Histologic confirmation was available for three cases. The subjects were between 15 and 54 years of age at diagnosis. Although the size of the sample is small, the mode of inheritance of fibrosing alveolitis within this family appeared to be dominant with incomplete penetrance. HLA typing showed that at least one of the affected siblings did not share any HLA haplotypes with other affected siblings in the third generation. This makes it unlikely that a disease gene would be in association with HLA genes on chromosome 6. In contrast, all affected siblings, as well as two as yet unaffected siblings, carried the immunoglobulin haplotype Gm 1. These studies indicate that familial fibrosing alveolitis in this family may be inherited by a dominantly inherited gene located on chromosome 14 close to the loci encoding for Gm.

Adolescent↗
PubMed1986

Extractable nuclear antigen (ENA) autoantibodies in SLE: an immunogenetic relationship with HLA, C4 and Bf alleles.

Sera from 36 subjects with systemic lupus erythematosus (SLE) were examined for extractable nuclear antigen (ENA) autoantibodies by immunoassay with the ribonucleoprotein (RNP) subset being determined by immunodiffusion. The prevalence of the genetic markers of HLA, the fourth complement component (C4) and properdin factor (Bf), which are all coded for within the major histocompatibility complex on chromosome 6 were analysed in relation to various parameters of these autoantibodies. The following associations were observed: The lowest ENA antibody titres of the RNP negative group were associated with HLA A9 (P less than 0.05), while the lowest RNA-ase sensitive ENA (RSE) subset antibody levels were associated with HLA Dr 1 (P less than 0.05). For the complement markers, C4 AQo was associated with the lowest affinity ENA antibodies (P less than 0.05), while the BF F allele and Fs phenotype had lower RSE antibody levels than did the S allele (P less than 0.05) and the SS phenotype (P less than 0.05) respectively. This study demonstrated diverse association between various MHC markers and ENA antibody parameters, indicating that there are distinctive immunogenetic influences over ENA autoantibodies in SLE.

Adolescent↗
PubMed1985

Different allotypes of C3 degrade at different rates.

To determine whether different forms of C3 degrade at different rates, we compared two strains of mice with a B10 background. The only difference was that one is C3A, while the other is C3B. These strains allow comparison of C3A and C3B without the added complication of differing C3 convertases. Sera from the two strains were incubated with zymosan and the degradation products were detected by immunofixation following electrophoresis in agarose. The rate of degradation of mouse C3B was more rapid than that of C3A. Differences in the rates of degradation could not be explained by differing concentrations of C3. We suggest that the genetic differences in C3 determine the decay rate following activation via the alternate pathway.

Alleles↗
PubMed1985

Susceptibility to IDDM is marked by MHC supratypes rather than individual alleles.

107 patients with insulin-dependent diabetes mellitus (IDDM) were typed for HLA A, B, C-, and DR antigens, and for complement C4A, C4B, and Bf alleles, and the results were compared with those of a combined reference group of 332 appropriately matched healthy subjects. Supratypes (allelic combinations) were identified from the phenotype of each group, and it was shown that the frequency of several supratypes is increased in patients with IDDM, in particular supratypes (A1 Cw7) B8 C4AQ0 C4B1 BfS DR3 (P = 0.0001), (A30 Cw-) B18 C4A3 C4BQ0 BfF1 DR3 (P = 0.0003), (A2 Cw3) B62 C4AR C4B2.9 BfS DR4 (P = 0.0002), and three other supratypes including DR4. It was also shown that increases in the frequency of individual alleles are secondary to increases in supratype frequency. Moreover, supratypes appeared to interact; the presence of two relevant supratypes being particularly important. The absolute risk of IDDM was approximately 0.5 in subjects who were homozygous for B18 C4A3 C4BQ0 BfF1 DR3. We concluded that genetic susceptibility is best recognized by MHC supratypes rather than isolated alleles, and that supratype combinations make the identification of even greater disease risk possible.

Alleles↗
PubMed1985

The molecular structure of different polymorphic forms of canine C3 and C4.

The subunit composition of different electrophoretic forms of canine C3 and C4 was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of reduced immune precipitates. Canine C4 comprises alpha, beta, and gamma chains of approximate molecular weight 90 000-95 000, 72 000, and 33 000, respectively. The molecular weight of the alpha chain of the C4 1 allelic product was approximately 95 000, but 90 000 for the C4 2 and C4 4 allotypes. No differences were observed in the molecular weights of the beta or gamma chains of any canine C4 phenotype tested. Canine C3 appears to be encoded by a single locus. The subunit composition comprises an alpha and beta chain with molecular weights of approximately 106 000 and 71 000, respectively. Unlike C4, no differences in the molecular weights of the subunits were observed in different electrophoretic forms of canine C3.

Alleles↗
PubMed1985

Complement C4 allotype association with and serum C4 concentration in an autoimmune disease in the dog.

Serum C4 concentrations and C4 allotypes were determined wherever possible on eight dogs with an autoimmune disorder characterized by antinuclear antibody (ANA) positivity, pyrexia, and seronegative arthritis. Three of the six dogs tested serially showed hypocomplementemia at disease onset with return to normal concentrations with clinical remission following steroid therapy. All five dogs C4 allotyped were phenotypically identical. The phenotype (C4-4) was significantly increased in the diseased dogs. Thus C4 allotype may provide a marker for susceptibility to development of an autoimmune disorder in the dog. Serum C4 concentrations may help in disease diagnosis and monitoring the effectiveness of therapy.

Animals↗