Phylogenetic analysis of 8 dermatophyte species using chitin synthase 1 gene sequences

Nucleotide sequences of chitin synthase 1 (CHS1) gene of eight species of dermatophytes, Arthroderma benhamiae, A. fulvum, A. grubyi, A. gypseum, A. incurvatum, A. otae, A. simii and A. vanbreuseghemii were obtained and analysed for their phylogenetic relationship. A 600-bp genomic DNA fragment of the CHS1 gene was amplified from these dermatophytes by polymerase chain reaction (PCR) and sequenced. The CHS1 nucleotide sequences of these eight dermatophyte species showed more than 85% similarity between the species. The phylogenetic analysis of their sequences revealed three clusters, the first cluster consisting of A. benhamiae, A. simii and A. vanbreuseghemii, the second cluster consisting of A. fulvum, A. gypseum and A. incurvatum, and the third cluster consisting of A. grubyi and A. otae. The phylogenetic analysis of CHS1 gene in this study will provide useful information for classification and understanding the evolution of these dermatophyte species.     

Synthesis and structure-activity relationships of 3,7-dimethyl-1-propargylxanthine derivatives, A2A-selective adenosine receptor antagonists

A series of 8-substituted derivatives of 3,7-dimethyl-1-propargylxanthine (DMPX) was synthesized and investigated as A2A adenosine receptor antagonists. Different synthetic strategies for the preparation of DMPX derivatives and analogues were explored. A recently developed synthetic procedure starting from 3-propargyl-5,6-diaminouracil proved to be the method of choice for the preparation of this type of xanthine derivatives. The novel compounds were investigated in radioligand binding studies at the high-affinity adenosine receptor subtypes A1 and A2A and compared with standard A2A adenosine receptor antagonists. Structure-activity relationships were analyzed in detail. 8-Styryl-substituted DMPX derivatives were identified that exhibit high affinity and selectivity for A2A adenosine receptors, including 8-(m-chlorostyryl)-DMPX (CS-DMPX, Ki A2A = 13 nM, 100-fold selective), 8-(m-bromostyryl)-DMPX (BS-DMPX, Ki A2A = 8 nM, 146-fold selective), and 8-(3,4-dimethoxystyryl)-DMPX (Ki A2A = 15 nM, 167-fold selective). These and other novel compounds are superior to the standard A2A adenosine receptor antagonists KF17837 (4) and CSC (5) with respect to A2A affinity and/or selectivity.     

Some properties of hemoglobin A2

While no significant physiologic function of hemoglobin A2 (Hb A2), the minor basic component of human hemoglobin, has been recognized, only its oxygen equilibria have been studied in detail. Since hemoglobin A2 and its oxidative denaturation product, hemichrome A2, bind to the red cell membrane, particularly to band 3, to a greater extent than do Hb A or hemichrome A, some of the properties of Hb A2 that might influence hemoglobin-membrane association were examined. Hemoglobin A2 exhibited slightly increased susceptibility to autoxidation to methemoglobin. No differences were noted between methemoglobins A and A2, including the rates of enzymatic reduction and stability of the heme-globin linkage. Oxyhemoglobin A2 had a slightly lower solubility in phosphate buffer than did hemoglobin A. While the hemichromes (prepared with phenylhydrazine) of hemoglobins A2 and A had the same optical spectra, the A2 hemichrome exhibited greater stability. It is suggested that the differences in products of oxidative denaturation may provide the basis for functional differences between hemoglobins A2 and A.     

Preferential adsorption, internalization and resistance to degradation of the major isoform of the Alzheimer's amyloid peptide, A beta 1-42, in differentiated PC12 cells

A central question in Alzheimer's disease (AD) is the role of amyloid in pathogenesis. Recent discoveries implicating the longer A beta 1-42 form of amyloid in pathogenesis led us to characterize the interaction of A beta with cells to elucidate differences that might account for these observations. We characterized the adsorption, internalization and degradation of radiolabeled A beta in NGF-differentiated PC12 cells under conditions that are not acutely toxic. All A beta peptides examined absorb to the surface of PC12 cells and are internalized; however the adsorption and internalization of A beta 1-42 is significantly greater than that of A beta 1-40 and A beta 1-28. The adsorption of A beta 1-42 is decreased by treatment of the cells with neuraminidase, but not heparitinase. The fate of the internalized A beta 1-42 is also very different than shorter A beta peptides; a fraction of the internalized A beta 1-42 accumulates intracellularly and is resistant to degradation for at least 3 days while A beta 1-40 and shorter peptides are eliminated with a half life of about 1 h. A beta 1-42 does not appear to inhibit lysosomal hydrolases, since A beta 1-28 is degraded at the same rate in the presence or absence of A beta 1-42. The intracellular A beta 1-42 is located in a dense organellar compartment and colocalizes with the lysosomal markers Lucifer Yellow and horseradish peroxidase. These data indicate that there are significant differences in the cell surface adsorption, internalization and catabolism of A beta 1-42 compared to A beta 1-40 and A beta 1-28. These differences may be important for the preferential accumulation of the longer A beta 1-42 isoform and its association with AD pathogenesis.     

Derivatives of the triazoloquinazoline adenosine antagonist (CGS 15943) having high potency at the human A2B and A3 receptor subtypes

The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1, 5-c]quinazolin-5-amine (CGS 15943) binds nonselectively to human A1, A2A, and A3 receptors with high affinity. Acylated derivatives and one alkyl derivative of the 5-amino group and other modifications were prepared in an effort to enhance A2B or A3 subtype potency. In general, distal modifications of the N5-substituent were highly modulatory to potency and selectivity at adenosine receptors, as determined in radioligand binding assays at rat brain A1 and A2A receptors and at recombinant human A3 receptors. In Chinese hamster ovary cells stably transfected with human A2B receptor cDNA, inhibition of agonist-induced cyclic AMP production was measured. An N5-(2-iodophenyl)acetyl derivative was highly selective for A2A receptors. An (R)-N5-alpha-methyl(phenylacetyl) derivative was the most potent derivative at A3 receptors, with a Ki value of 0.36 nM. A bulky N5-diphenylacetyl derivative, 13, displayed a Ki value of 0. 59 nM at human A3 receptors and was moderately selective for that subtype. Thus, a large, nondiscriminating hydrophobic region occurs in the A3 receptor in proximity to the N5-substituent. A series of straight-chain N5-aminoalkylacyl derivatives demonstrated that for A2B receptors the optimal chain length occurs with three methylene groups, i.e., the N5-gamma-aminobutyryl derivative 27 which had a pA2 value of 8.0 but was not selective for A2B receptors. At A1, A2A, and A3 receptors however the optimum occurs with four methylene groups. An N5-pivaloyl derivative, which was less potent than 27 at A1, A2A, and A3 receptors, retained moderate potency at A2B receptors. A molecular model of the 27-A2B receptor complex based on the structure of rhodopsin utilizing a "cross-docking" procedure was developed in order to visualize the environment of the ligand binding site.     

S100A1 utilizes different mechanisms for interacting with calcium-dependent and calcium-independent target proteins

While previous studies have identified target proteins that interact with S100A1 in a calcium-dependent manner as well as target proteins that interact in a calcium-independent manner, the molecular mechanisms of S100A1-target protein interaction have not been elucidated. In this study, point and deletion mutants of S100A1 were used to investigate the contribution of carboxyl terminal amino acids to S100A1 interaction with calcium-dependent and calcium-independent target proteins. First, a recombinant rat S100A1 protein (recS100A1) expressed in bacteria exhibited physical and chemical properties indistinguishable from native S100A1. Next, proteins lacking the carboxyl-terminal nine residues of recS100A1 (Delta85-93), or containing alanine substitutions at Phe 88 (F88A), Phe 89 (F89A), or Trp 90 (W90A), both Phe 88 and Phe 89 (F88/89A), or all three aromatic residues (F88/89A-W90A) were recombinantly expressed. Like recS100A1, F88A, F89A, and W90A proteins interacted with phenyl-Sepharose in a calcium-dependent manner. However, the Delta85-93 protein did not interact with phenyl-Sepharose, indicating that a phenyl-Sepharose-binding region (PSBR) of recS100A1 had been disrupted. The F88/89A and F88/89A-W90A proteins exhibited reduced calcium-dependent interaction with phenyl-Sepharose when compared with recS100A1, demonstrating that the carboxyl-terminal aromatic residues Phe 88, Phe 89, and Trp 90 comprise the PSBR of S100A1. Fluorescence studies showed that the Delta85-93 protein exhibited reduced calcium-dependent interaction with the dodecyl CapZ peptide, TRTK, while W90A bound TRTK with a Kd of 5.55 microM. These results demonstrate that the calcium-dependent target protein-binding site and the PSBR are indistinguishable. In contrast to the calcium-dependent target TRTK, activation of the calcium-independent target protein aldolase A by the point and deletion mutant S100A1s was indistinguishable from native S100A1. These results demonstrate that carboxyl-terminal residues are not required for S100A1 modulation of calcium-independent target protein aldolase A. Alltogether, these results indicate that S100A1 utilizes distinct mechanisms for interaction with calcium-independent and calcium-dependent target proteins.     

Metabolism of dynorphin A1-13 in human CSF

In-vitro incubation of human cerebrospinal fluid (CSF) obtained from patients ranging from 22-78 years with 10 microM of dynorphin A1-13 (Dyn A1-13) resulted in several cleavage products. Dyn A1-12 and A2-13 were identified as the major CSF metabolites by matrix-assisted laser desorption mass spectrometry (LD-MS). Further metabolites were Dyn A1-6, A2-12 and A4-12. LD-MS further suggested the formation of Dyn A1-8, A1-7, A1-10, A7-10, A3-12, A7-12, A3-13, A7-13 and A8-13. The metabolic half-life of Dyn A1-13 at 37 degrees C was approximately 2.5 h (range 1.75-8.5 h), compared to less than one minute in plasma. The half-life of Dyn A1-13 decreased markedly with age or age-associated processes (n = 20, r2 = 0.498). Noncompartmental kinetic analysis in the absence or presence of enzyme inhibitors (leucinethiol 10 microM, captopril 100 microM and GEMSA 20 microM) suggested that Dyn A1-13 is mainly metabolized by carboxypeptidase to A1-12 (51%) and by aminopeptidases to A2-13 (35%). The generation of A1-6 (13%) was only detected under enzyme inhibition. The extent of conversion into the main metabolites did not follow an age-associated trend, thus over-all enzyme levels but no specific enzymatic systems are elevated with age.     

Differentiation of Arthroderma spp. by random amplification of polymorphic DNA (RAPD) and Southern hybridization

To develop the molecular differentiation analysis of dermatophytes, we carried out RAPD and Southern hybridization analyses using genomic DNAs of six Arthroderma species, including A. fulvum, A. grubyi, A. gypseum, A. incurvatum, A. otae and A. racemosum. The RAPD analysis gave different band patterns specific to each of the six Arthroderma fungi. However, minor differences in the banding patterns were observed between the strains of plus (+) and minus (-) mating types of A. gypseum, A. fulvum and A. incurvatum. Southern blot analysis using a probe (1S) obtained from A. grubyi DNA gave specific bands only in the DNA samples of A. grubyi and A. incurvatum. On the other hand, Southern blot analysis using a probe (C3) obtained from A. otae DNA gave specific bands in all six Arthroderma species examined, and the size of the bands were specific to each species. These findings indicate that RAPD and Southern hybridization analyses are useful in the differentiation of these Arthroderma species.     

Simple one-step procedure for the separation of apolipoproteins A1 and A2 by high-performance liquid chromatography

A simple assay method for apolipoproteins apo A1 and apo A2 by HPLC is introduced. The simple one-step method is based on fractionation of apo A1 and apo A2 from other serum proteins which are precipitated at 100 degrees C and removed by centrifugation. The apo A1 and apo A2 which remain in solution can be recovered and resolved by size-exclusion chromatography without ultracentrifugation and delipidation by an organic solvent. This makes sample preparation easier. The recoveries of apo A1 and apo A2 were 104.26% and 101.04%; the precision (C.V.%) of apo A1 and apo A2 was 0.88 and 1.63 respectively.     

Relevance of the finite element method to optimize fixed partial denture design. Part I. Influence of the size of the connector on the magnitude of strain

One hundred forty seven sera of children in Gifu Prefecture, were tested for positive rate of neutralization antibody against Coxsackievirus group A (Cox. A). The results were as follows; 1. The positive rate of antibodies against Cox. A 4, Cox. A 10 and Cox. A 16 were detected in over 45%, but the positive rate of antibody against Cox. A 2 thought isolated rarely, was detected in the same rate. However, both the rate of isolation and positive rate of antibody against Cox. A 8 showed lower levels than other types. 2. The positive rate of antibodies against Coxsackievirus group A were different in every areas in the prefecture. In Seino area, the positive rate of antibodies of Cox. A 2, Cox. A 8 and Cox. A 10 were higher than in other areas. In Gifu area, the positive rate of antibodies against Cox. A 4 and Cox. A 16 were highest but the positive rate of antibody against Cox. A 8 was the lowest than other areas. In Hida(G) area, the positive rate of antibodies against Cox. A 2 and Cox. A 16 were the lowest levels than other areas. In Hide(T) area, the positive rate of antibodies against Cox. A 4 and Cox. A 10 of these viruses, were the lowest than other areas. 3. The positive rate of antibodies by age group, was showed the same pattern in Cox. A 2, Cox. A 4 and Cox. A 10, that is, there was a raise with age and reached to 80-90%. In Cox. A 8, the positive rate of antibody rose with age, but the highest positive rate of antibody reached only 35.5%. In Cox. A 16, the positive rate in 0-1 year olds showed a higher positive rate in 44%, which rose with age, but the rate dropped once at 6-7 age and again rose and reached to 86.7% in the 8-9 age group.     

Antigenic relationships among oral Actinomyces isolates, Actinomyces naeslundii genospecies 1 and 2, Actinomyces howellii, Actinomyces denticolens, and Actinomyces slackii

Antigenic relatedness among human strains of oral Actinomyces and similar isolates from cattle has been analyzed by agglutination and immunoblotting. Whole cell agglutination placed A. viscosus serotype II, A. naeslundii serotypes II and III, Actinomyces NV, and strains from numerical taxomonic clusters C1, C2, C3, C4, and C6 into a single group. A. viscosus serotype I cross-reacted weakly with this group. A naeslundii serotype I strains and the cattle isolates Actinomyces denticolens and Actinomyces howellii were distinct. The agglutination results for A. slackii were equivocal. Immunoblots of cell wall extracts developed with non-absorbed sera showed cross-reactivity (23% to 90% antigenic similarity) among all of the strains tested, including A. israelii. The range of antigenic similarities among the group which included strains of A. viscosus serotype II, the A. naeslundii serotypes, and clusters C1, C2, C3, C4, and C6 was from 39% to 89%. Immunoblotting showed that A. howellii and A. denticolens were between 39% and 72% similar to A. naeslundii and A. viscosus. Absorption of antisera with A. israelii cell walls removed antibodies recognizing antigens common to Actinomyces and made the sera more specific. Immunoblotting with absorbed sera supported the grouping and separation of strains shown by agglutination. In some cases, serotypes could be included into a specific taxonomic cluster. A. naeslundii serotype II and Actinomyces NV most closely resembled cluster C1 strains, and A. naeslundii serotype III resembled cluster C1 strains, and A. naeslundii serotype I and A. viscosus serotype I were included into clusters C5 and C7, respectively. The results support a recent proposal that strains of A. viscosus serotype II, A. naeslundii serotypes II and III, and Actinomyces NV be included into A. naeslundii genospecies 2, that A. naeslundii serotype I should be designated A. naeslundii genospecies 1, and that A. viscosus serotype I should be retained distinct from A. naeslundii, as A. viscosus.     

Accelerated neutrophil apoptosis in mice lacking A1-a, a subtype of the bcl-2-related A1 gene

To elucidate the role of A1, a new member of the Bcl-2 family of apoptosis regulators active in hematopoietic cell apoptosis, we established mice lacking A1-a, a subtype of the A1 gene in mice (A1-a-/- mice). Spontaneous apoptosis of peripheral blood neutrophils of A1-a-/- mice was enhanced compared with that of either wild-type mice or heterozygous mutants (A1-a+/- mice). Neutrophil apoptosis inhibition induced by lipopolysaccharide treatment in vitro or transendothelial migration in vivo observed in wild-type mice was abolished in both A1-a-/- and A1-a+/- animals. On the other hand, the extent of tumor necrosis factor alpha-induced acceleration of neutrophil apoptosis did not differ among A1-a-/-, A1-a+/-, and wild-type mice. The descending order of A1 mRNA expression was wild-type, A1-a+/-, and A1-a-/-. Taken together, these results suggest that A1 is involved in inhibition of certain types of neutrophil apoptosis.     

Sporogonic development of Plasmodium yoelii in five anopheline species

Sporogonic development of Plasmodium yoelii yoelii 17XNL was examined in 5 species of Anopheles mosquitoes; A. albimanus, A. dirus, A. freeborni, A. gambiae, and A. stephensi. The kinetics of ookinete formation differed among species. In A. freeborni, A. gambiae, and A. stephensi, mature ookinetes formed synchronously at 8 hr, then quickly subsided. In A. albimanus and A. dirus, ookinete formation was more protracted, and ookinete densities peaked from 12 to 24 hr. Losses in parasite abundance during the conversion of ookinetes to oocysts were similar between A. dirus and A. gambiae (55- and 41-fold losses, respectively) but were an order of magnitude less in A. stephensi (1.3-fold loss). Ookinete conversion to oocysts in A. albimanus was nil. Melanotic encapsulation of oocysts occurred in 25-30% of infected A. gambiae and A. dirus. Melanized parasites in A. gambiae at days 7-10 were small (10 microns diameter) and retort-shaped, whereas melanized parasites in A. dirus were generally as large as normal oocysts (60 microns) and many were incompletely melanized. Melanotic encapsulation did not occur in A. stephensi, A. freeborni, or A. albimanus. On day 16, sporozoites were present in the salivary glands of A. freeborni, A. gambiae, and A. stephensi, but only half of mosquitoes were mature oocysts also had gland infections. When present in the glands, sporozoites were successfully transmitted to mice via mosquito bite. Parasite populations were not normally distributed in any mosquito species but were adequately described by a negative binomial type of distribution.     

Potentially reactive cyclic carbamate metabolite of the antiepileptic drug felbamate produced by human liver tissue in vitro

To gain insights into the different forms of modified amyloid beta peptides (A beta) in the Alzheimer disease (AD) and Down syndrome (DS) brain, we used two-site ELISAs with antibodies specific for isomerized (i.e. A beta with L-isoaspartate at positions 1 and 7) and pyroglutamate-modified (i.e. A beta beginning with pyroglutamate at position 3) forms of A beta to quantitate the levels of these different A beta peptides in formic acid extracts of AD and DS frontal cortex. Despite variations in the proportions of distinct forms of A beta in AD and DS frontal cortex, the major species of A beta in these samples were A betaN3(pyroGlu)-42 as well as A beta x-42 (where x is a residue at position 2 or less in A beta), whereas isomerized A beta was a minor species. Further, the levels of isomerized and pyroglutamate-modified forms of A beta terminating at amino acid 42 were higher than those ending at amino acid 40. The abundance of the distinct forms of A beta reported here in formic acid extracts of AD and DS frontal cortex suggests that these A beta species could play important roles in the deposition of A beta in AD and DS brains.     

Peritoneal malformation with intestinal dystopia--a case report

Four subtypes of adenosine receptors have recently been cloned from thyroid, brain and testis. In this review we have summarised properties of these purinergic receptors. The cloned A1 and A2 subtypes are probably similar or identical to receptors that exist on cardiac and vascular tissues, respectively. A comparison of the amino acid sequences of A1, A2a, and A2b receptors reveals several stretches of conserved amino acids that are unique to adenosine receptors, primarily in the membrane spanning regions. Species differences in A1 receptors indicate that minor changes in receptor structure can produce marked changes in ligand binding properties and may facilitate the identification of amino acids involved in ligand recognition. A confusing A1 receptor subclassification system of putative A1a, A1b, and A3 subtypes has emerged based on subtle rank order potency differences for various ligands among tissues. cDNAs corresponding to these A1 subtypes have not yet been isolated. Atrial A1 receptors activate K+ channels and inhibit adenylyl cyclase. These two pathways appear to be independently up and down regulated, suggesting the existence either of atrial A1 receptor subtypes or of differential regulation of the coupling of a single receptor to distinct GTP binding proteins. An adenosine receptor distinct from A1 and A2 receptors has been cloned from testis and designated TGPCR, or A3, although it differs from the pharmacologically defined A3 receptor. We suggest that the current A1/A3 receptor subtype nomenclature be abandoned and superseded by a nomenclature based solely on receptor cDNAs. In addition to the cloned adenosine receptors, a novel A4 subtype has been proposed based on pharmacological and electrophysiological criteria.(ABSTRACT TRUNCATED AT 250 WORDS)     

An atypical case of arising of some parietal branches of the Arteria iliaca interna in man

In the pelvis of a 78 year old man there have been observed deviations in the origin and course os some parietal branches of the A. iliaca interna dextra. Apart from this typically arising and passing branches (the A. glutaea superior dextra, the A. glutaea inferior dextra, the A. umbilicalis dextra) an atypical stem--the Truncus pudendo-obturatorius--comes out of the A. iliaca interna dextra. This stem divides into the A. obturatoria dextra and the A. pudenda accessoria. The A. pudenda accessoria goes through the pelvis and through the fissure between Symphysis and the Diaphragma urogenitale on the Radix penis as the A. dorsalis penis dextra. The A. pudenda interna dextra comes out of the A. pudenda accessoria in a quite atypical way. It enters the fossa ischiorectalis through the fissure in the hind part of the Arcus tendineus m. levatoris ani ventrally from the Spina ischiadica. Its terminal part goes to the right Corpus cavernosum penis as the A. profunda penis dextra. The parietal branches of the A. iliaca interna sinistra arise and go in a typical way. The A. pudenda accessoria is not formed on the left side of the pelvis.     

Autotransplantation of the spleen in the rat: donor leukocytes of the splenic fragment survive implantation to migrate and proliferate in the host

A rabbit liver UDP-glucuronosyltransferase cDNA that is related to human and rat UGT1A7 has been identified. The predicted amino acid sequence of the UGT1A71 displays 80% similarity to that encoded by human HP4 (UGT1A9), but 81% to that predicted for human UGT1A7 and 77% to the rat UGT1A7 (UGTA2). The exons encoding human UGT1A7 and rat UGTA2 are the seventh of the series of cassette exons that flank the 3' common exon series of the UGT1A locus. Southern blot analysis demonstrates that the exon sequence encoding UGT1A71 is part of a larger cluster of highly related genes. The UGT1A71 RNA is expressed in both neonatal and adult liver, and unlike rat UGT1A2 which is inducible with Ah receptor ligands such as polycyclic aromatic hydrocarbons, rabbit UGT1A7 is not regulated when animals are exposed to these inducers. Following expression of UGT171 in COS-1 cells, glucuronidation activity was identified for small phenolic molecules like 4-nitrophenyl, bulky phenols as represented by 4-hydroxybiphenol and octylgallate, as well as 4-hydroxyestrone. In addition, UGT1A71 possesses catalytic activity toward tertiary amines like the tricyclic antidepressant imipramine. The pattern of UGT1A71 glucuronidation is similar to that observed for human UGT1A9, except tertiary amines are not subject to glucuronidation by human UGT1A9. Glucuronidation of tertiary amines is catalyzed principally by human UGT1A4 as well as rabbit UGT1A4. Although rabbit UGT1A7 catalyzes the formation of quarternary ammonium glucuronides, the Vmax is considerably less than that observed for rabbit UGT1A4. Overall, the characterization of rabbit UGT1A7 suggests that this protein represents the ortholog of the human UGT1A7, which to date has not been identified.     

Bovine natural killer activity against virally infected cells inhibited by monoclonal antibodies

Forty-four monoclonal antibodies (mAbs) were evaluated for their ability to alter natural killer (NK) cell lysis of virally infected target cells. Six of the mAbs inhibited the lysis of the target cells, while one of the mAbs enhanced lysis. Four of the inhibitory mAbs, CACT26A, CACT16A, CACTB45A and MUC76A, had very marked activity. These mAbs with inhibitory or enhancing activity recognized (1) WC2 molecules (CACTB44A, CACT16A, CACT26A) present on putative NK cells, (2) molecules on granulocytes, monocytes, a subpopulation of lymphocytes (CACTB45A and TH2A), (3) CD11a (MUC76A), and a protein of CD3 (MM1A).     

Polysaccharide biotechnology--a Cinderella subject

Histotyping of HLA I antigens in 100 patients with keratoconus. Europeoids of the Chelyabinsk district, and of 701 controls (donors listed in the regional register) showed an increased incidence of HLA A28, B12, and B15, a decreased incidence of HLA B8, B13, and complete absence of HLA A11. Estimation of HLA haplotypes in keratoconus showed an increased incidence of haplotypes A1-B5 (relative risk RR = 5.9), A2-B15 (RR = 3.34), A2-B27 (RR = 2.12), and A9-B21 (RR = 4.13) and decreased incidence of A1-B8 (RR = 0.31). The incidence of incomplete phenotypes was 27%. The most incident of incomplete phenotypes was A3-B35. Reliably linked HLA haplotypes A3-B7, A2-B27, A9-B21, and A9-B35 were typical of men with keratoconus, whereas A2-B21 haplotype was characteristic of the female patients.