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Biomedical subjects

A Bateman

Publications and source records attributed to A Bateman.

At least 55 records · Page 3Linked to original sources
PubMed1999

The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease.

Most cases of autosomal dominant polycystic kidney disease (ADPKD) are the result of mutations in the PKD1 gene. The PKD1 gene codes for a large cell-surface glycoprotein, polycystin-1, of unknown function, which, based on its predicted domain structure, may be involved in protein-protein and protein-carbohydrate interactions. Approximately 30% of polycystin-1 consists of 16 copies of a novel protein module called the PKD domain. Here we show that this domain has a beta-sandwich fold. Although this fold is common to a number of cell-surface modules, the PKD domain represents a distinct protein family. The tenth PKD domain of human and Fugu polycystin-1 show extensive conservation of surface residues suggesting that this region could be a ligand-binding site. This structure will allow the likely effects of missense mutations in a large part of the PKD1 gene to be determined.

Amino Acid Sequence↗
PubMed1999

Pfam 3.1: 1313 multiple alignments and profile HMMs match the majority of proteins.

Pfam is a collection of multiple alignments and profile hidden Markov models of protein domain families. Release 3.1 is a major update of the Pfam database and contains 1313 families which are available on the World Wide Web in Europe at http://www.sanger.ac.uk/Software/Pfam/ and http://www.cgr.ki.se/Pfam/, and in the US at http://pfam.wustl.edu/. Over 54% of proteins in SWISS-PROT-35 and SP-TrEMBL-5 match a Pfam family. The primary changes of Pfam since release 2.1 are that we now use the more advanced version 2 of the HMMER software, which is more sensitive and provides expectation values for matches, and that it now includes proteins from both SP-TrEMBL and SWISS-PROT.

Algorithms↗
PubMed1999

Long-term blood product transfusion support for patients with myelodysplastic syndromes (MDS): cost analysis and complications.

Patients with myelodysplastic syndromes (MDS) frequently become dependent on blood transfusions. We analyzed the total transfusion support required, and its complications and cost, following the diagnosis of MDS (total period = 79.7 patient-years) in 50 patients followed at the Minneapolis VA Medical Center. From diagnosis of MDS to transformation to AML or death (the MDS phase), 41 patients (82%) required transfusions. The median numbers of transfused blood products per patient per year of follow-up in the MDS phase were: packed red blood cells (pRBC), 11.1 (range, 0-91.3) units, random donor platelets (RDP), 6.8 (range, 0-581) units, and single donor apheresis platelet packs (SDP): 0 (range, 0-40) collections. In the AML phase (time from diagnosis of secondary AML to death or last follow-up), median transfusion requirements per patient (n = 5) were 24 (range, 8-88) units pRBC, 94 (range, 24-480) units RDP and 3 (range, 0-19) collections of SDP. Overall, 80% of patients required either special processing or selection of blood products, had reactions to blood products or required premedications (specified/complicated transfusions); 94% of all pRBC and 97% of all platelet transfusions were specified/complicated. The median cost of transfusions per patient was $4048 (range, $0-73210) during the MDS phase and $13210 (range, $5288-59010) during the AML phase. During the MDS phase, the median cost was $4877 (range, $0-67050) per patient-year of follow-up; the major proportion of this cost was for pRBC transfusions. Long-term support with frequent transfusions for MDS usually requires specially selected or processed blood products, and is associated with a high incidence of transfusion reactions. This study provides baseline data on the costs of transfusion support for MDS, and can be used for comparing resource utilization and costs of long-term transfusion support (supportive care) with growth factor therapy or disease-modifying modalities such as allogeneic transplantation.

Blood Transfusion↗
PubMed1999

Effectiveness of partial hospitalization in the treatment of borderline personality disorder: a randomized controlled trial.

OBJECTIVE: This study compared the effectiveness of psychoanalytically oriented partial hospitalization with standard psychiatric care for patients with borderline personality disorder. METHOD: Thirty-eight patients with borderline personality disorder, diagnosed according to standardized criteria, were allocated either to a partially hospitalized group or to a standard psychiatric care (control) group in a randomized controlled design. Treatment, which included individual and group psychoanalytic psychotherapy, was for a maximum of 18 months. Outcome measures included the frequency of suicide attempts and acts of self-harm, the number and duration of inpatient admissions, the use of psychotropic medication, and self-report measures of depression, anxiety, general symptom distress, interpersonal function, and social adjustment. Data analysis used repeated measures analysis of covariance and nonparametric tests of trend. RESULTS: Patients who were partially hospitalized showed a statistically significant decrease on all measures in contrast to the control group, which showed limited change or deterioration over the same period. An improvement in depressive symptoms, a decrease in suicidal and self-mutilatory acts, reduced inpatient days, and better social and interpersonal function began at 6 months and continued until the end of treatment at 18 months. CONCLUSIONS: Psychoanalytically oriented partial hospitalization is superior to standard psychiatric care for patients with borderline personality disorder. Replication is needed with larger groups, but these results suggest that partial hospitalization may offer an alternative to inpatient treatment.

Adult↗
PubMed1999

The Caenorhabditis elegans genes egl-27 and egr-1 are similar to MTA1, a member of a chromatin regulatory complex, and are redundantly required for embryonic patterning.

We show here that two functionally redundant Caenorhabditis elegans genes, egl-27 and egr-1, have a fundamental role in embryonic patterning. When both are inactivated, cells in essentially all regions of the embryo fail to be properly organised. Tissue determination and differentiation are unaffected and many zygotic patterning genes are expressed normally, including HOX genes. However, hlh-8, a target of the HOX gene mab-5, is not expressed. egl-27 and egr-1 are members of a gene family that includes MTA1, a human gene with elevated expression in metastatic carcinomas. MTA1 is a component of a protein complex with histone deacetylase and nucleosome remodelling activities. We propose that EGL-27 and EGR-1 function as part of a chromatin regulatory complex required for the function of regional patterning genes.

Amino Acid Sequence↗
PubMed1998

Pfam: multiple sequence alignments and HMM-profiles of protein domains.

Pfam contains multiple alignments and hidden Markov model based profiles (HMM-profiles) of complete protein domains. The definition of domain boundaries, family members and alignment is done semi-automatically based on expert knowledge, sequence similarity, other protein family databases and the ability of HMM-profiles to correctly identify and align the members. Release 2.0 of Pfam contains 527 manually verified families which are available for browsing and on-line searching via the World Wide Web in the UK at http://www.sanger.ac.uk/Pfam/ and in the US at http://genome.wustl. edu/Pfam/ Pfam 2.0 matches one or more domains in 50% of Swissprot-34 sequences, and 25% of a large sample of predicted proteins from the Caenorhabditis elegans genome.

Amino Acid Sequence↗
PubMed1998

Structure and distribution of pentapeptide repeats in bacteria.

We report the discovery of a novel family of proteins, each member contains tandem pentapeptide (five residue) repeats, described by the motif A(D/N)LXX. Members of this family are both membrane bound and cytoplasmic. The function of these repeats is uncertain, but they may have a targeting or structural function rather than enzymatic activity. This family is most common in cyanobacteria, suggesting a function related to cyanobacterial-specific metabolism. Although no experimental information is available for the structure of this family, it is predicted that the tandem pentapeptide repeats will form a right-handed beta-helical structure. A structural model of the pentapeptide repeats is presented.

Amino Acid Sequence↗
PubMed1998

The DUTT1 gene, a novel NCAM family member is expressed in developing murine neural tissues and has an unusually broad pattern of expression.

A new member of the NCAM family mapping to 3p12 has been isolated and predicted to be arranged in five immunoglobulin-like domains and three fibronectin-like domains which are particularly homologous to L1. There is a transmembrane domain and a long cytoplasmic region with no detectable homology to other sequences. Although less closely related to DCC, another family member, both share a loop of positively charged amino acids within the first immunoglobulin domain, unique to these two members of this very large gene family. Preliminary studies of expression in mouse embryos support an inferred role in neural development, but the observation of widespread gene expression in adult human tissues indicates that this protein has additional functions to those performed in neural cells.

Amino Acid Sequence↗
PubMed1998

Privatized Medicaid managed care in Massachusetts: disposition in child and adolescent mental health emergencies.

Data from child and adolescent emergency mental health screening episodes prior and subsequent to privatized Medicaid managed care in Massachusetts are used to investigate the relationship between payer source and disposition and to compare the match between clinical need and disposition level of care. Having Medicaid as the payer in the post-Medicaid managed care period decreased the odds of hospitalization by nearly 60%. None of the clinical need variables that contributed to hospitalization for Medicaid episodes in the pre-Medicaid managed care period were significant in the post-Medicaid managed care period. Multiple forces shaping professional standards, decision making, and quality of care are described. Public sector agencies must lay the groundwork for comprehensive evaluation prior to the implementation of privatized Medicaid managed care initiatives.

Adolescent↗
PubMed1998

RK-2: a novel rabbit kidney defensin and its implications for renal host defense.

Defensins are endogenous antimicrobial peptides. We demonstrated recently the existence of RK-1, a defensin-like peptide in rabbit kidneys. Defining the renal-defensin system is an essential step toward understanding how the kidney responds to infection. Here, using a combination of high-performance liquid chromatography, matrix-assisted laser desorption time-of-flight mass spectrometry, amino acid compositional analysis, and microsequence analysis, we show that the rabbit kidney contains a novel alpha-defensin-like peptide, RK-2. This work establishes the existence of a new subfamily of alpha-defensins in the kidney.

Amino Acid Sequence↗
PubMed1998

Granulins: the structure and function of an emerging family of growth factors.

The granulin/epithelin motif defines a family of structurally unique proteins, of great evolutionary antiquity, which have been implicated as regulators of cell growth. Recurrent in granulin research are the surprising parallels between the granulin and EGF systems. Both are cysteinerich peptides of approximately 6 kDa that can modify cell growth. They show similar, but not identical, biological activities, although granulin/epithelin peptides do not bind EGF receptors; the three-dimensional folds of granulin and EGF are partially superimposible; and the precursors for mammalian granulin/epithelins and EGF are both organized as multiple repeats of conserved cysteine modules. Given the dissimilarity between amino acid sequences of members of the granulin/epithelin family and EGF-related peptides, the parallelism between the two systems probably represents convergent evolution towards related solutions to common biological problems. The granulin/epithelin precursor gene is expressed throughout the body, but its expression is predominantly in epithelial and haematopoietic cells. There is a great deal of versatility in the means by which cells process and handle the granulin/epithelin precursor. In some instances, the precursor is secreted intact (Zhou et al. 1993), and in others it is stored in a vesicular organelle, such as the sperm acrosome (Baba et al. 1993a). It may be processed into small 6-kDa peptides, which, in the neutrophil, can also be stored in vesicles (Bateman et al. 1990, Couto et al. 1992). The 6-kDa peptide forms, the intact precursor, and related proteins such as TGFe, regulate the growth of epithelial and mesenchymal cells. Epithelial cells express putative receptors for granulin/epithelin peptides and TGFe (Culouscou et al. 1993, Parnell et al. 1995). Thus, although much remains to be clarified, granulin/epithelin polypeptides and related proteins are emerging as widely distributed potential autocrine and paracrine growth modulating factors for epithelial and mesenchymal cells.

Amino Acid Sequence↗
PubMed1997

Distant homology recognition using structural classification of proteins.

Protein structure prediction is arguably the biggest unsolved problem of structural biology. The notion of the number of naturally occurring different protein folds being limited allows partial solution of this problem by the use of fold recognition methods, which "thread" the sequence in question through a library of known protein folds. The fold recognition methods were thought to be superior to the distant homology recognition methods when there is no significant sequence similarity to known structures. We show here that the Structural Classification of Proteins (SCOP) database, organizing all known protein folds according their structural and evolutionary relationships, can be effectively used to enhance the sensitivity of the distant homology recognition methods to rival the "threading" methods. In the CASP2 experiment, our approach correctly assigned into existing SCOP superfamilies all of the six "fold recognition" targets we attempted. For each of the six targets, we correctly predicted the homologous protein with a very similar structure; often, it was the most similar structure. We correctly predicted local alignments of the sequence features that we found to be characteristic for the protein superfamily containing a given target. Our global alignments, extended manually from these local alignments, also appeared to be rather accurate.

Amino Acid Sequence↗
PubMed1997

A member of the immunoglobulin superfamily in bacteriophage T4.

We report a prediction that the highly immunogenic outer capsid (Hoc) protein of the prokaryotic phage T4 contains three tandem immunoglobulin-like domains. Immunoglobulin-like folds have previously been identified in prokaryotic proteins but these share no recognizable sequence similarity with eukaryotic immunoglobulin superfamily (IgSF) folds, and may represent products of convergent evolution. In contrast, the Hoc immunoglobulin-like folds are proposed, based on immunoglobulin-like sequence consensus matches detected by hidden Markov modeling. We propose that the Hoc immunoglobulin-like domains and eukaryotic immunoglobulin-like domains are likely to be related by divergence from a common ancestor.

Amino Acid Sequence↗
PubMed1997

Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains.

PKD1 is the major locus of the common genetic disorder autosomal dominant polycystic kidney disease (ADPKD). Analysis of the predicted protein sequence of the human PKD1 gene, polycystin, shows a large molecule with a unique arrangement of extracellular domains and multiple putative transmembrane regions. The precise function of polycystin remains unclear with a paucity of mutations to define key structural and functional domains. To refine the structure of this protein we have cloned the genomic region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA and has greater complexity with 54 exons compared with 46 in man. Comparative analysis of the predicted protein sequences shows a lower level of homology than in similar studies with identity of 40 and 59% similarity. However key structural motifs including leucine rich repeats (LRR), a C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A region of homology with the sea urchin REJ protein was also confirmed in Fugu but found to extend over 1000 amino acids. Several highly conserved intra- and extra-cellular regions, with no known sequence homologies, that are likely to be of functional importance were detected. The likely structure of the membrane associated region has been refined with similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels highlighted over part of this area. The overall protein structure has therefore been clarified and this comparative analysis derived structure will form the basis for the functional study of polycystin and its individual domains.

Amino Acid Sequence↗
PubMed1996

Outline structure of the human L1 cell adhesion molecule and the sites where mutations cause neurological disorders.

The L1 cell adhesion molecule has six domains homologous to members of the immunoglobulin superfamily and five homologous to fibronectin type III domains. We determined the outline structure of the L1 domains by showing that they have, at the key sites that determine conformation, residues similar to those in proteins of known structure. The outline structure describes the relative positions of residues, the major secondary structures and residue solvent accessibility. We use the outline structure to investigate the likely effects of 22 mutations that cause neurological diseases. The mutations are not randomly distributed but cluster in a few regions of the structure. They can be divided into those that act mainly by changing conformation or denaturing their domain and those that alter its surface properties.

Amino Acid Sequence↗