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1.
Int J Biol Macromol ; 266(Pt 2): 131079, 2024 May.
Article in English | MEDLINE | ID: mdl-38537860

ABSTRACT

This study investigates the effects of SCG embedded into biodegradable polymer blends and aimed to formulate and characterise biomass-reinforced biocomposites using spent coffee ground (SCG) as reinforcement in PHB/PLA polymer blend. The effect of SCG filler loading and varying PHB/PLA ratios on the tensile properties and morphological characteristics of the biocomposites were examined. The results indicated that tensile properties reduction could be due to its incompatibility with the PHB/PLA matrixSCG aggregation at 40 wt% content resulted in higher void formation compared to lower content at 10 wt%. A PHB/PLA ratio of 50/50 with SCG loading 20 wt% was chosen for biocomposites with treated SCG. Biological treatment of SCG using Phanerochaete chrysosporium CK01 and Aspergillus niger DWA8 indicated P. chrysosporium CK01 necessitated a higher moisture content for optimum growth and enzyme production, whereas the optimal conditions for enzyme production (50-55 %, w/w) differed from those promoting A. niger DWA8 growth (40 %, w/w). SEM micrographs highlighted uniform distribution and effective wetting of treated SCG, resulting in improvements of tensile strength and modulus of biocomposites, respectively. The study demonstrated the effectiveness of sustainable fungal treatment in enhancing the interfacial adhesion between treated SCG and the PHB/PLA matrix.


Subject(s)
Aspergillus niger , Coffee , Hydroxybutyrates , Polyesters , Polyesters/chemistry , Hydroxybutyrates/chemistry , Coffee/chemistry , Aspergillus niger/drug effects , Tensile Strength , Polymers/chemistry
2.
J Hosp Infect ; 132: 133-139, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36309203

ABSTRACT

BACKGROUND: Mycobacterium abscessus (MABS) group are environmental organisms that can cause infection in people with cystic fibrosis (CF) and other suppurative lung diseases. There is potential for person-to-person airborne transmission of MABS among people with CF attending the same care centre. Ultraviolet light (band C, UV-C) is used for Mycobacterium tuberculosis control indoors; however, no studies have assessed UV-C for airborne MABS. AIM: To determine whether a range of UV-C doses increased the inactivation of airborne MABS, compared with no-UVC conditions. METHODS: MABS was generated by a vibrating mesh nebulizer located within a 400 L rotating drum sampler, and then exposed to an array of 265 nm UV-C light-emitting diodes (LED). A six-stage Andersen Cascade Impactor was used to collect aerosols. Standard microbiological protocols were used for enumerating MABS, and these quantified the effectiveness of UV-C doses (in triplicate). UV-C effectiveness was estimated using the difference between inactivation with and without UV-C. FINDINGS: Sixteen tests were performed, with UV-C doses ranging from 276 to 1104 µW s/cm2. Mean (±SD) UV-C effectiveness ranged from 47.1% (±13.4) to 83.6% (±3.3). UV-C led to significantly greater inactivation of MABS (all P-values ≤0.045) than natural decay at all doses assessed. Using an indoor model of the hospital environment, it was estimated that UV-C doses in the range studied here could be safely delivered in clinical settings where patients and staff are present. CONCLUSION: This study provides empirical in-vitro evidence that nebulized MABS are susceptible to UV-C inactivation.


Subject(s)
Mycobacterium abscessus , Mycobacterium tuberculosis , Humans , Ultraviolet Rays , Respiratory Aerosols and Droplets , Disinfection/methods
4.
Colorectal Dis ; 18(6): O206-9, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26880360

ABSTRACT

AIM: It is controversial whether a high or low ligation of the inferior mesenteric artery (IMA) is superior. The former allows an extended lymph node clearance whereas the latter preserves the distal vascular supply via the left colic artery (LCA). Apical lymph node dissection of the IMA (ALMA) harvests nodal tissue along the IMA proximal to the LCA whilst performing a low ligation. This anatomically replicates the oncological benefit of high ligation and the vascular preservation of low ligation. Our study evaluates the nodal yield of ALMA and the short-term outcome of this technique. METHOD: We retrospectively studied 19 patients with sigmoid or rectal cancer who underwent curative surgical resection with ALMA. All ALMAs were performed with a standard technique previously described (Kobayashi et al., Surg Endosc 2005, 20:563-9; Sekimoto et al. Surg Endosc 2010, 25:861-6) . The lymph node yield from the dissection (the ALMA specimen) was compared with the total lymph node yield. Data on the LCA anatomy, time required to perform ALMA, complications and postoperative recovery were evaluated. RESULTS: ALMA was successful in 18 patients. Median postoperative hospitalization was 5 (2-26) days without ALMA-related morbidity or mortality. The median lymph node yield was 20 (9-41) and a median of 14.3 (0-80)% were harvested with ALMA. Two patients not having neoadjuvant chemoradiotherapy had fewer than 12 lymph nodes, excluding nodes harvested from ALMA. The average time required for ALMA was 18 min. CONCLUSION: ALMA is a safe and feasible technique, allowing extended lymphadenectomy without sacrificing the LCA. In this small group of patients none were upstaged due to cancerous involvement of the proximal nodes.


Subject(s)
Lymph Node Excision/methods , Lymph Nodes/pathology , Mesenteric Artery, Inferior/surgery , Rectal Neoplasms/surgery , Sigmoid Neoplasms/surgery , Aged , Colon/blood supply , Colon/surgery , Female , Humans , Ligation , Lymph Nodes/surgery , Lymphatic Metastasis , Male , Middle Aged , Rectal Neoplasms/pathology , Retrospective Studies , Sigmoid Neoplasms/pathology , Treatment Outcome
5.
Hernia ; 17(6): 805-7, 2013 Dec.
Article in English | MEDLINE | ID: mdl-22911516

ABSTRACT

Foreign bodies causing perforation of hernias are extremely uncommon with only a few cases reported in the literature. Here, we present a case of a patient with ingestion of a foreign body, which was initially managed expectantly but developed a perforation due to the foreign body impacting and causing perforation of an irreducible inguinal hernia. Management of this condition usually involves resection of the involved loop of bowel with repair of the hernia defect at the time of surgery. Patients with ingested foreign bodies who have irreducible hernias have altered anatomy and should be considered for early surgical intervention to prevent complications.


Subject(s)
Bone and Bones , Chickens , Foreign-Body Migration/diagnosis , Hernia, Inguinal/complications , Aged , Animals , Foreign-Body Migration/complications , Humans , Male
6.
Anim Genet ; 36(1): 1-6, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15670124

ABSTRACT

Myostatin, or growth and differentiation factor 8 (GDF8), has been identified as the factor causing a phenotype known as double muscling, in which a series of mutations render the gene inactive, and therefore, unable to regulate muscle fibre deposition. This phenotype occurs at a high frequency in some breeds of cattle such as Belgian Blue and Peidmontese. Phylogenetic analysis has shown that there has been positive selection pressure for non-synonymous mutations within the myostatin gene family, around the time of the divergence of cattle, sheep and goats, and these positive selective pressures on non-ancestral myostatin are relatively recent. To date, there have been reports of nine mutations in coding regions of myostatin that cause non-synonymous changes, of which three cause missense mutations, including two in exon 1 and one in exon 2. The remaining six mutations, located in exons 2 and 3, result in premature stop codons, which are the mutations responsible for the double-muscling phenotype. Unfortunately, breed management problems exist for double-muscled cattle, such as birthing difficulties, which can be overcome through genetically controlled breeding programmes, as shown in this review.


Subject(s)
Breeding , Cattle/genetics , Transforming Growth Factor beta/genetics , Animals , Breeding/economics , Breeding/methods , Muscle, Skeletal/abnormalities , Myostatin
7.
Tissue Antigens ; 63(3): 263-9, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14989717

ABSTRACT

Nucleotide polymorphisms of the C4 genes were investigated by direct sequencing of seven different homozygous typing cells from the 10IHW panels. Two novel sequences were identified within the C4d region of the C4 genes. Our sequencing analyses extend previous findings suggesting that a recombination hot spot is likely to have occurred between codon positions 1157 and 1186 within the C4d region. The classification of electrophoretically defined C4A and C4B alleles can be further subtyped by sequencing. Because the central major histocompatibility complex region that carries various copies of the C4 gene has been associated with a range of disorders; further analysis at the sequence level within the C4 locus may provide informative genetic markers for the investigation of disease-associated polymorphisms.


Subject(s)
Alleles , Complement C4/genetics , Polymorphism, Genetic , Recombination, Genetic/genetics , Base Sequence , Cell Line , Exons/genetics , Humans , Introns/genetics , Molecular Sequence Data , Sequence Analysis, DNA
8.
Tissue Antigens ; 60(1): 77-83, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12366786

ABSTRACT

In order to examine the relationship between corneodesmosin (CDSN) and psoriasis we have determined the presence of CDSN polymorphisms by DNA sequencing in (a) nine B-LCL cell lines of major histocompatibility complex ancestral haplotypes known to be associated with psoriasis vulgaris including 13.1AH, 46.1AH, 46.2 and 57.1AH, and in (b) a group of 267 unrelated individuals comprising Japanese psoriasis patients (n = 101) and Japanese subjects without the disease (n = 166). Three novel CDSN gene sequences were identified. In addition, we have classified the 18 alleles into seven main groups based on phylogeny of non-synonymous substitutions. However, we have found no statistically significant differences between the patients and the unaffected individuals in any of these groups. These findings indicate that CDSN is not a major psoriasis susceptibility gene.


Subject(s)
Glycoproteins/genetics , Haplotypes/genetics , Histocompatibility Antigens Class I/genetics , Major Histocompatibility Complex/genetics , Psoriasis/genetics , Alleles , Base Sequence , Genetic Linkage/genetics , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Humans , Intercellular Signaling Peptides and Proteins , Japan/epidemiology , Molecular Sequence Data , Polymorphism, Genetic/genetics , Psoriasis/epidemiology
9.
Hum Immunol ; 62(3): 279-85, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11250045

ABSTRACT

The genomic matching technique (GMT) improves survival following bone marrow transplantation (BMT) between unrelated donor and recipient pairs correlating with a decrease in incidence and severity of graft-versus-host disease (GvHD). The principles of this technique are based on the duplication and polymorphic characteristics of the major histocompatibility complex (MHC). Specifically, the beta block GMT matches for a 300 kb region that contains the human leukocyte antigen (HLA-B and -C) genes as well as other non-HLA genes such as the natural killer cell receptor ligand PERB11 (MIC). The block contains two large segmental duplications. One results in two PERB11 genes (11.1 and 11.2), the other in two class I genes (HLA-B and -C). With the complete sequencing of the class I region of the MHC in different haplotypes, we can now show that the beta block GMT profiles reflect amplification of the duplicated PERB11 segments and not the duplicated segments containing HLA-B and -C, and yet provide a signature that characterizes the entire block rather than individual loci.


Subject(s)
HLA-B Antigens/genetics , HLA-C Antigens/genetics , Histocompatibility Antigens Class I/genetics , Proteins/genetics , Base Sequence , Bone Marrow Transplantation , DNA Primers , DNA, Complementary , Gene Amplification , Gene Duplication , Genetic Techniques , Histocompatibility Testing , Humans , Molecular Sequence Data , Polymorphism, Genetic , RNA, Long Noncoding , RNA, Untranslated , Sequence Analysis, DNA , Treatment Outcome
10.
Eur J Immunogenet ; 27(5-6): 397-426, 2000.
Article in English | MEDLINE | ID: mdl-11029610

ABSTRACT

Cell panels have been used extensively in studies of polymorphism and disease associations within the major histocompatibility complex (MHC), but the results from these panels require continuous updates with the increasing availability of novel data. We present here an updated table of the typings of the 10IHW and 4AOH panels. Local data included are HFE, HERV-K(C4) and six microsatellites telomeric of HLA-A. Typings for class I, MICA (PERB11.1), MICB (PERB11.2), XA, XB, LMP2 and 10 microsatellites reported by others have also been consolidated in this table. The tabulation shows that the length of conservation in the human MHC is even more extensive than previously thought. Human MHC ancestral haplotypes are inherited as a conserved region of genomic sequence spanning some 6-8 megabases from the HLA class II region and beyond the HLA class I region up to and including the HFE gene. Numerous examples of historical recombinations were also observed.


Subject(s)
HLA-A Antigens/genetics , Telomere/genetics , Cell Line , Conserved Sequence , Haplotypes , Humans , Recombination, Genetic , Sequence Analysis, DNA
11.
J Mol Evol ; 50(4): 359-65, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10795827

ABSTRACT

Several highly polymorphic sequences are present in the beta block of the MHC, especially HLA-B, HLA-C, PERB11.1 (MICA), and PERB11.2 (MICB). It is now apparent that the polymorphism of PERB11.1 is of the same order as that of HLA-A, -B, and -C and it has been suggested that PERB11 could explain some of the disease associations previously attributed to HLA-B. Phylogenetic analysis of PERB11 alpha-domain sequences demonstrates relationships with HLA-B cross-reactive serogroups. In contrast, the transmembrane polymorphisms do not appear to be associated with either PERB11 or HLA-B. These data indicate that PERB11 and HLA-B have evolved in concert from their common ancestors and that the transmembrane polymorphisms have arisen independently and more recently. MHC disease associations will need to be reviewed in the light of mechanisms such as receptor binding and signaling.


Subject(s)
Evolution, Molecular , HLA-B Antigens/genetics , Polymorphism, Genetic , Proteins/genetics , Base Sequence , Histocompatibility Antigens Class I , Humans , Molecular Sequence Data , Phylogeny
12.
Clin Exp Immunol ; 119(3): 553-8, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10691930

ABSTRACT

The susceptibility genes for psoriasis remain to be identified. At least one of these must be in the major histocompatibility complex (MHC) to explain associations with alleles at human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and C4. In fact, most of these alleles are components of just two ancestral haplotypes (AHs) designated 13.1 and 57.1. Although relevant MHC gene(s) could be within a region of at least 4 Mb, most studies have favoured the area near HLA-B and -C. This region contains a large number of non-HLA genes, many of which are duplicated and polymorphic. Members of one such gene family, PERB11.1 and PERB11.2, are expressed in the skin and are encoded in the region between tumour necrosis factor and HLA-B. To investigate the relationship of PERB11.1 alleles to psoriasis, sequence based typing was performed on 97 patients classified according to age of onset and family history. The frequency of the PERB11.1*06 allele is 44% in type I psoriasis but only 7% in controls (Pc = 0.003 by Fisher's exact test, two-tailed). The major determinant of this association is a single nucleotide polymorphism (SNP) within intron 4. In normal and affected skin, expression of PERB11 is mainly in the basal layer of the epidermis including ducts and follicles. PERB11 is also present in the upper keratin layers but there is relative deficiency in the intermediate layers. These findings suggest a possible role for PERB11 and other MHC genes in the pathogenesis of psoriasis.


Subject(s)
Histocompatibility Antigens Class I/genetics , Proteins/genetics , Psoriasis/genetics , Base Sequence , Haplotypes , Humans , Molecular Sequence Data , Polymorphism, Single Nucleotide , Proteins/immunology , Psoriasis/immunology , Psoriasis/pathology , RNA, Long Noncoding , RNA, Untranslated , Skin/immunology , Skin/pathology
13.
J Appl Toxicol ; 19(4): 285-90, 1999.
Article in English | MEDLINE | ID: mdl-10439344

ABSTRACT

Decontamination of chemical agents from the skin uses both dry and wet decontamination processes. Recent studies have shown that wet decontamination frequently results in stratum corneum hydration. To evaluate the hydration effect of wet decontamination on the skin barrier function and hence on the decontamination efficiency, a series of comparative studies were carried out on human skin contaminated with the nerve agent simulant diethylmalonate, using decontamination media having different salinity and surfactants. The results showed that, compared to non-decontaminated skin, remnant diethylmalonate on decontaminated skin penetrated at an accelerated rate in the immediate 2 h following decontamination. This transient enhancement effect, ranging from 20 to 98%, was depended on the nature of the decontamination media used and was more obvious in skin samples that were decontaminated 1 h postexposure. All decontamination media exhibited this effect, with the greatest enhancement observed in the following order: anionic surfactant > cationic surfactant > non-ionic surfactant > deionized water > 0.9% saline > 9% saline.


Subject(s)
Body Water/metabolism , Decontamination/methods , Malonates/pharmacokinetics , Skin Absorption/physiology , Skin/metabolism , Aged , Aged, 80 and over , Benzethonium/pharmacology , Cadaver , Humans , Male , Middle Aged , Skin/drug effects , Skin Absorption/drug effects , Sodium Dodecyl Sulfate/pharmacology
14.
J Heart Lung Transplant ; 18(3): 226-30, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10328148

ABSTRACT

It is argued that HLA matching is not worthwhile in heart transplantation. However, transplanting HLA compatible hearts enhances graft survival and should significantly reduce infection and malignancies related to aggressive immunosuppression. It is our view that the problem is technical and we offer a potential solution.


Subject(s)
Heart Transplantation , Histocompatibility Testing , Graft Survival , Heart Transplantation/immunology , Heart Transplantation/mortality , Humans , Immunosuppression Therapy/adverse effects , Survival Rate
15.
Immunol Rev ; 167: 275-304, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10319268

ABSTRACT

The genomic region encompassing the Major Histocompatibility Complex (MHC) contains polymorphic frozen blocks which have developed by local imperfect sequential duplication associated with insertion and deletion (indels). In the alpha block surrounding HLA-A, there are ten duplication units or beads on the 62.1 ancestral haplotype. Each bead contains or contained sequences representing Class I, PERB11 (MHC Class I chain related (MIC) and human endogenous retrovirus (HERV) 16. Here we consider explanations for co-occurrence of genomic polymorphism, duplication and HERVs and we ask how these features encode susceptibility to numerous and very diverse diseases. Ancestral haplotypes differ in their copy number and indels in addition to their coding regions. Disease susceptibility could be a function of all of these differences. We propose a model of the evolution of the human MHC. Population-specific integration of retroviral sequences could explain rapid diversification through duplication and differential disease susceptibility. If HERV sequences can be protective, there are exciting prospects for manipulation. In the meanwhile, it will be necessary to understand the function of MHC genes such as PERB11 (MIC) and many others discovered by genomic sequencing.


Subject(s)
Disease Susceptibility/immunology , Disease Susceptibility/virology , Gene Duplication , Haplotypes/immunology , Major Histocompatibility Complex/genetics , Retroviridae/genetics , Animals , Base Sequence , Humans , Major Histocompatibility Complex/immunology , Molecular Sequence Data , Retroviridae/immunology
16.
Hum Immunol ; 60(2): 171-6, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10027786

ABSTRACT

Block matching is a valuable tool for selecting donors for bone marrow transplantation. Identical, electrophoretic profiles of unrelated bone marrow donor-recipient pairs have been shown to be associated with long-term survival and a reduction of graft versus host disease (GVHD). This study was undertaken to determine the sequences of the PCR products which are generated. PCR products obtained with beta-block primers following the amplification of DNA extracted from cell lines homozygous for 7.1 and 8.1 ancestral haplotypes were cloned and sequenced. The PCR products were characterised and the beta block profiles reconstructed. The data indicate that the profiles consist of homoduplexes and heteroduplexes which are formed by the products of probably 3 different sequence locations.


Subject(s)
HLA Antigens/genetics , Polymerase Chain Reaction/methods , Cell Line, Transformed , HLA Antigens/classification , Haplotypes , Humans
17.
Am J Respir Crit Care Med ; 158(6): 1825-30, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9847274

ABSTRACT

Asthma is a genetically complex disease, and the investigation of putative linkages to candidate loci in independent populations is an important part of the gene discovery process. This study investigated the linkage of microsatellite markers in the 5q and 11q regions to asthma-associated quantitative traits in 121 Australian Caucasian nuclear families. The families were recruited on the basis of a child proband: a cohort of 95 randomly recruited families of unselected probands (n = 442 subjects) and a cohort of 26 families of probands selected on the basis of severe symptomatic asthma (n = 134 subjects). The quantitative traits assessed included serum levels of total IgE and specific IgE to house dust mite and mixed grass, blood eosinophil counts, and the dose-response slope (DRS) of FEV1 to histamine provocation. Multipoint linkage analysis using Haseman-Elston sib-pair methods provided evidence of significant linkage between the chromosome 5q markers and loge total serum IgE levels, specific serum IgE levels, and loge blood eosinophil counts. The chromosome 11q markers showed evidence of significant linkage to specific serum IgE levels. Neither region demonstrated significant linkage to the loge DRS to histamine. Phenotypes were residualized for age and sex. These data are consistent with the existence of loci regulating asthma-associated quantitative traits in both the 5q31-33 and 11q13 chromosomal regions.


Subject(s)
Asthma/genetics , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 5/genetics , Genetic Linkage/genetics , Adolescent , Adult , Animals , Australia , Bronchial Provocation Tests , Bronchoconstrictor Agents/administration & dosage , Child , Chromosome Mapping , Cohort Studies , Dose-Response Relationship, Drug , Eosinophils/pathology , Female , Forced Expiratory Volume/drug effects , Genetic Markers , Histamine/administration & dosage , Humans , Immunoglobulin E/blood , Leukocyte Count , Longitudinal Studies , Male , Microsatellite Repeats/genetics , Mites/immunology , Phenotype , Poaceae/immunology
18.
Singapore Med J ; 39(1): 42-4, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9557106

ABSTRACT

During the Japanese Occupation of Singapore and Malaya (1941-1945), Singapore was renamed Syonan (or Syonanto) and Malaya was called Malai (or Marai; Marei). On 27 April 2603 (1943) the Japanese Military Administration established. The Marai Ika Daigaku (Syonan Medical College) at the Tan Tock Seng Hospital (Hakuai Byoin), Syonan. The Medical College shifted to the General Hospital, Malacca in February 2604 (1944) where it functioned till the end of the Japanese Occupation in September 2605 (1945).


Subject(s)
Schools, Medical , History, 20th Century , Humans , Japan , Malaysia , Singapore , Warfare
19.
Hum Immunol ; 59(1): 56-62, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9544240

ABSTRACT

Conventional matching is based on numbers of alleles shared between donor and recipient. This approach, however, ignores the degree of relationship between alleles and haplotypes, and therefore the actual degree of difference. To address this problem, we have compared family members using a block matching technique which reflects differences in genomic sequences. All parents and siblings had been genotyped using conventional MHC typing so that haplotypes could be assigned and relatives could be classified as sharing 0, 1 or 2 haplotypes. We trained an Artificial Neural Network (ANN) with subjects from 6 families (85 comparisons) to distinguish between relatives. Using the outputs of the ANN, we developed a score, the Histocompatibility Index (HI), as a measure of the degree of difference. Subjects from a further 3 families (106 profile comparisons) were tested. The HI score for each comparison was plotted. We show that the HI score is trimodal allowing the definition of three populations corresponding to approximately 0, 1 or 2 haplotype sharing. The means and standard deviations of the three populations were found. As expected, comparisons between family members sharing 2 haplotypes resulted in high HI scores with one exception. More interestingly, this approach distinguishes between the 1 and 0 haplotype groups, with some informative exceptions. This distinction was considered too difficult to attempt visually. The approach provides promise in the quantification of degrees of histocompatibility.


Subject(s)
HLA Antigens/genetics , Haplotypes/genetics , Histocompatibility Testing/methods , Neural Networks, Computer , Electrophoresis, Agar Gel , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Humans , Immunoblotting , Polymerase Chain Reaction
20.
Fold Des ; 3(1): 27-37, 1998.
Article in English | MEDLINE | ID: mdl-9502318

ABSTRACT

BACKGROUND: PERB11 is a multicopy polymorphic gene family found in association with HLA Class I genes within the major histocompatibility complex (MHC). Although its function is unknown, PERB11 has sequence similarities to HLA Class I and other related proteins. To explore the possible functional roles for PERB11, homology models have been constructed using both HLA Class I and Class I-like protein structures as templates. RESULTS: The models show that PERB11.1 appears to have an unusual distribution of charged residues that potentially give the molecule a distinct polarity. Furthermore, a cluster of negatively charged residues in the traditional P2 site may form a novel binding site for a positively charged ligand such as a metal ion or complex. Other charged residues line the floor and walls of the cleft and are able to form salt bridges, reminiscent of the closed cleft of the Class I-like mouse neonatal Fc receptor structure. The closely related PERB11.2 family has a different arrangement of charged residues in the cleft, but these residues are still able to form salt bridges. Unlike HLA Class I, the majority of polymorphic positions in the PERB11 family occur outside the cleft and on the surface of the molecule. CONCLUSIONS: Homology models for PERB11 suggest that the structure is capable of associating with beta2 microglobulin or a similar molecule. Furthermore, not all of the potential glycosylation sites suggested by the PERB11 sequences appear viable. Importantly, the models suggest that the molecule has a less accessible cleft than HLA Class I and is not, therefore, able to bind peptides. Other small ligands, including metal ions, might be bound, however.


Subject(s)
Histocompatibility Antigens Class I/genetics , Models, Chemical , Multigene Family , Proteins/genetics , Amino Acid Sequence , Binding Sites , Evaluation Studies as Topic , Glycosylation , Histocompatibility Antigens Class I/chemistry , Histocompatibility Antigens Class I/metabolism , Humans , Metals/metabolism , Molecular Sequence Data , Protein Binding , Proteins/chemistry , Proteins/metabolism , RNA, Long Noncoding , RNA, Untranslated , Sequence Homology, Amino Acid , beta 2-Microglobulin/metabolism
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