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T Gibson

Publications and source records attributed to T Gibson.

At least 55 records · Page 3Linked to original sources

The KH module has an alpha beta fold.

The KH module has recently been identified in a number of RNA associated proteins including vigilin and FMR1, a protein implicated in the fragile X syndrome. In this work, NMR spectroscopy was used to determine the secondary structure in solution of a KH domain (repeat 5 from vigilin). Almost complete assignments were obtained for the 1H and 15N resonances using uniform 15N-labeling of the protein combined with homo-nuclear 2D 1HNMR and 3D 15N correlated 1H NMR. On the basis of NOE patterns, secondary chemical shifts and amide solvent exposure, the secondary structure consists of an antiparallel three stranded beta sheet connected by two helical regions. This domain may also be stabilized by an appended C-terminal helix which is common to many but not all members of the KH family.

Amino Acid Sequence↗

Bacterial infections: the arthritis of leprosy.

Arthritis is a common feature of leprosy and contributes to disability. Direct invasion of joints and bones by mycobacteria may lead to a destructive arthritis in lepromatous disease. The infective process may involve few or many joints. Reactional states may occur spontaneously but usually after the initiation of anti-mycobacterial treatment. In both the type 1 reaction of borderline case and the type 2 reaction of the lepromatous disease, intense inflammation may occur at sites of infection. The immunology of the reactions is different but they share clinical features including a polyarthritis which may resemble rheumatoid disease. The joint disease may be chronic or relapsing, affecting the wrists and small joints of the hands in particular. Radiological erosions may occur. Mycobacterium leprae is not found in the synovium in this pattern of arthritis. Further study of this phenomenon might yield useful information above the mechanism of joint inflammation in other rheumatic diseases.

Arthritis, Reactive↗

The prevalence of rheumatoid arthritis in affluent and poor urban communities of Pakistan.

Using previously applied methods a survey of joint symptoms was undertaken among 4232 adults, evenly distributed between affluent and poor areas of Karachi, Pakistan. Only six cases of definite rheumatoid arthritis (RA) (1958 ARA criteria) were identified in the 245 persons who complained of joint problems of at least 4 weeks duration. The prevalence was 0.9 [confidence interval (CI) 0.21-3.61] and 1.98 (CI 0.55-5.1) per thousand in the poor and affluent districts, respectively. These were substantially less than prevalence rates reported in the West but were similar to figures derived from other developing countries. There was no obvious impact of current living standards on the findings. The relative paucity of older female subjects in both the affluent and poor communities may account at least in part for the low rates observed. The infrequency of rheumatoid nodules in Southern Asians with RA illustrates the difficulty of applying existing diagnostic criteria to this community.

Adolescent↗

Diltiazem induces remission of calcinosis in scleroderma.

There is no widely accepted treatment for the calcinosis which occurs in scleroderma and dermatomyositis. We report a case of a 62-yr-old woman with active scleroderma complicated by tuberose calcinosis. The calcinosis, which had previously been unchanged for several years, regressed over a 2-yr period during which diltiazem was used to treat hypertension. This effect could not be explained by altered disease activity or renal function but, we suggest, may be due to inhibition of calcium influx into cells. This treatment merits further evaluation.

Calcinosis↗

The frequency of known diabetes, hypertension and ischaemic heart disease in affluent and poor urban populations of Karachi, Pakistan.

The high frequency of diabetes mellitus and coronary artery disease among people of South Asian extraction living in the West is well established. The prevalence of these disorders in Southern Asia is less certain. No previous attempt has been made to estimate their occurrence in Pakistan. In order to compare the prevalence of known diabetes mellitus, hypertension and ischaemic heart disease between affluent and poor urban communities in Pakistan, a survey of consecutive households was undertaken in a relatively prosperous and a poor area in Karachi. Information was obtained on 4232 adults evenly distributed between the two areas. Body weight and height were measured in 199 healthy subjects at the two sites. The prevalence of known diabetes in the affluent population was 4.5%, significantly higher than 1.8% in the poor area (p < 0.001). A maximal prevalence of 25% was seen in the affluent community aged 55-64. Diabetes was more common in females in both populations. The overall prevalence of hypertension was similar in the two areas although significantly more frequent in the middle aged and affluent. A history of ischaemic heart disease occurred in 1.9% of the affluent and 0.6% of the poor (p = 0.003). Healthy subjects were heavier and more obese in the richer community. Thus the susceptibility of South Asian populations to diabetes and ischaemic heart disease is also apparent in an affluent segment of Pakistani society. The phenomenon is not attributable simply to urbanization. Obesity is probably an important contributory factor. The economic implications for developing South Asian countries are serious.

Adolescent↗

The dimerization stability of the HLH-LZ transcription protein family is modulated by the leucine zippers: a CD and NMR study of TFEB and c-Myc.

In the HLH-LZ protein family, the helix-loop-helix DNA-binding dimerization domain is followed in the sequence by a leucine zipper motif. The precise function of this second dimerization domain is still unclear, since the HLH motif of a subset of this family has been shown to be necessary and sufficient for dimerization. However, deletion and mutagenesis studies of the leucine zipper in various HLH-LZ proteins have shown a clear influence of this motif on homo- and heterodimerization. In this paper, we present a structural characterization of synthetic peptides encompassing the leucine zipper sequences of c-Myc and TFEB, using circular dichroism, analytical ultracentrifugation, and nuclear magnetic resonance. We show that the different ability of the synthetic leucine zippers of c-Myc and TFEB to homodimerize at neutral pH reflects the different dimerization properties reported for the entire proteins. The TFEB protein is known to form homodimers. c-Myc, on the other hand, does not homodimerize in vivo, but is mostly found in heterodimeric complexes with Max, another protein of the HLH-LZ family. Accordingly, our results show that the TFEB peptide homodimerizes at neutral pH whereas the Myc peptide dimerizes to a comparable amount only at acidic pH and high ionic strength. Both synthetic peptides are far less stable than leucine zippers of the b-ZIP family. The relative stability of the two leucine zippers and the factors which stabilize the dimer formation are discussed.

Amino Acid Sequence↗

Recognition of the mRNA selenocysteine insertion sequence by the specialized translational elongation factor SELB.

In Escherichia coli the unusual amino acid selenocysteine is incorporated cotranslationally at an in-frame UGA codon. Incorporation of selenocysteine relies, in part, on the interaction between a specialized elongation factor, the SELB protein, and a cis-acting element within the mRNA. Boundary and toeprint experiments illustrate that the SELB-GTP-Sec-tRNA(Sec) ternary complex binds to the selenoprotein encoding mRNAs fdhF and fdnG, serving to increase the concentration of SELB and Sec-tRNA(Sec) on these mRNAs in vivo. Moreover, toeprint experiments indicate that SELB recognizes the ribosome-bound message and that, upon binding, SELB may protrude out of the ribosomal-mRNA track so as to approach the large ribosomal subunit. The results place the mRNA-bound SELB-GTP-Sec-tRNA(Sec) ternary complex at the selenocysteine codon (as expected) and suggest a mechanism to explain the specificity of selenocysteine insertion. Cis-acting mRNA regulatory elements can tether protein factors to the translation complex during protein synthesis.

Bacterial Proteins↗

Arthritis of leprosy.

An inflammatory polyarthritis has been previously described in leprosy but accounts of the clinical characteristics have varied. All patients with joint symptoms admitted to a leprosy centre over 5 months were examined by a rheumatologist. Of 48 acute admissions, 20 (42%) had a symmetrical polyarthritis affecting the wrists and fingers. This was strikingly similar to RA in appearance. The arthritis occurred exclusively in patients with reactions mainly during anti-mycobacterial treatment. The clinical features of the joint disorder were identical in Type I (associated with alterations in immune status) and Type II (erythema nodosum leprosum) reactions. Synovial tissue from one patient revealed no mycobacteria. Four of five hand X-rays suggested small erosions of the finger joints.

Acute Disease↗

The clinical, serologic and radiologic features of rheumatoid arthritis in ethnic black Zimbabwean and British Caucasian patients.

OBJECTIVE: To compare the clinical, serologic and radiologic expression of rheumatoid arthritis (RA) in UK Caucasian and ethnic black patients from Zimbabwe. METHODS: Standardized protocols and assessment criteria were used to study 84 black patients with no non-Bantu antecedents and 84 UK Caucasian patients with RA (matched for disease duration, sex and age). RESULTS: Articular manifestations of RA were less severe in the black patients with RA from Zimbabwe as shown by less early morning stiffness (p = 0.001), fewer patients with > or = 3 active joints (p = 0.01), fewer joint deformities (p = 0.004) and better grip strength (p = 0.001) in comparison to the white patients with RA from the UK. Caucasian patients had a higher frequency of extraarticular manifestations (p = 1 x 10(-6)) including rheumatoid nodules (p = 0.0001), Raynaud's (p = 0.01) and Sicca syndrome (p = 0.001). Toxic effects from disease modifying antirheumatic drugs occurred less frequently in black patients (p = 0.0002). More white patients had Ro and La antibodies. The radiologic changes in the black patients were less severe than those in the white patients. The distribution of erosions in hands and feet were different in the 2 groups of patients studied. There were no differences between the urban and rural black patients but a more detailed study involving a large number of patients is required to confirm this observation. CONCLUSION: Black patients with RA from Zimbabwe have a disease that is clinically and radiologically less severe with fewer extraarticular features when compared to UK white patients.

Adult↗

Intrinsic spinal cord lesions in 2 patients with ankylosing spondylitis.

Two men with longstanding ankylosing spondylitis (AS) developed spastic paraparesis. Extensive investigation failed to find a cause and it was concluded that some acute undetermined intrinsic spinal cord lesion had occurred. Similar descriptions in the past have been attributed to associated multiple sclerosis, but we suggest that the finding may represent a rare complication of AS with an unknown etiology.

Diagnosis, Differential↗

Nature of the ribosomal mRNA track: analysis of ribosome-binding sites containing different sequences and secondary structures.

The ribosomal mRNA track was investigated by toeprinting 30S ribosomes, in the presence or absence of tRNA, using a variety of different ribosome-binding sites. We found that: (1) the ribosome, by itself, recognizes the mRNA translational initiation site; (2) the ribosomal mRNA track makes extensive contact with mRNA independent of tRNA and the start codon; (3) ribosome-mRNA complexes are less stable than complexes containing tRNA; and (4) toeprinting can be used to analyze the contour of the ribosomal mRNA track, yielding information on its "height" as well as its "length" dimension. Examination of several ribosome-binding sites, including those containing very stable secondary structure, indicated that the "height" of the mRNA track is quite roomy, while the nucleotide distance between the site of Shine-Dalgarno annealing, the P site, and the 3'-edge of the mRNA track is fixed. The data suggest a mechanism for tethering regulatory elements to the ribosome during translation.

Base Sequence↗

The PH domain: a common piece in the structural patchwork of signalling proteins.

The 'pleckstrin homology' domain is an approximately 100-residue protein module that has recently been added to the domain catalogue of signalling proteins. For this review we have made an extensive database search using a profile search method, and found a number of additional proteins that may contain PH domains. The PH domain is present in many kinases, isoforms of phospholipase C, GTPases, GTPase-activating proteins and nucleotide-exchange factors, including such proteins as Vav, Dbl and Bcr, and there are two PH domains in a guanine-nucleotide releasing factor of Ras. Many PH-domain-containing proteins interact with GTP-binding proteins. We have also identified a PH domain in beta-adrenergic receptor kinase exactly in the region that has already been shown to be involved in binding to the beta and gamma subunits of a heterotrimeric G protein. This suggests that PH domains may be involved in interactions with GTP-binding proteins.

Amino Acid Sequence↗

Irreversible blindness in systemic lupus erythematosis.

We describe a patient with systemic lupus erythematosis and renal involvement and who developed visual impairment in the absence of hypertension and anti-cardiolipin antibodies. This was attributed to occlusive vascular disease and choroidal infarction in the context of active lupus. Complete and irreversible blindness developed rapidly despite treatment and the patient died of cerebral haemorrhage 2 months after discharge.

Adult↗

The diagnosis of Poncet's disease.

Two cases of polyarthritis in young people with extra-articular tuberculosis are described. The clinical features were consistent with the concept of Poncet's disease. After synovial biopsy one patient proved to have tuberculous peripheral arthritis. This observation raised doubts about the diagnosis in the other patient. Multiple joints may be simultaneously infected with Mycobacterium tuberculosis and Poncet's disease, if it exists, should not be entertained in the absence of synovial biopsy.

Adolescent↗

Holism, care and nursing: points of reflection during the evolution of a philosophy of nursing statement.

An exploration of the diversity and complexity of perspectives from which holism and care can legitimately be constructed. The preparation of a document for accreditation of a proposed pre-registration Bachelor of Nursing award was the impetus for this exploration. School members deemed holism and care to be central to our philosophy of nursing statement, however, difficulty arose in determining a shared understanding of these notions. Through reflective deliberation and a review of the literature, the authors attempted to unravel the range of meanings given to these problematic terms.

Education, Nursing, Baccalaureate↗

Risk of schizophrenia in adults born after obstetric complications and their association with early onset of illness: a controlled study.

OBJECTIVE: To determine whether obstetric complications occur to excess in the early histories of individuals who go on to develop schizophrenia when compared with controls, and to seek clinical correlates of any such excess. DESIGN: Contemporaneous maternity hospital records were identified and extracted verbatim, and these extracts evaluated for obstetric complications by two independent assessors who were blind to subjects' status. SUBJECTS: 65 patients having an ICD-9 diagnosis of schizophrenia, the records of the previous same sex live birth being deemed to be those of a control subject. MAIN OUTCOME MEASURE: Presence of one or more obstetric complications recorded in maternity notes of patients and controls. RESULTS: When two recognised scales for specifying obstetric complications were used the patients with schizophrenia were significantly more likely than controls to have experienced at least one obstetric complication (odds ratio 2.44, 95% confidence interval 1.08 to 6.03). Patients also showed a greater number and severity of and total score for obstetric complications, fetal distress being the only complication to occur to significant individual excess (present in five (8%) patients, absent in controls). There was a marked sex effect, male patients being more vulnerable (odds ratio 4.24, 1.39 to 12.90) to such complications. Obstetric complications in patients were unrelated to family history or season of birth but were associated with a significantly younger age at onset of illness (mean difference--4.5 years,--1.2 to--7.8 years). CONCLUSIONS: Patients with schizophrenia, particularly males, have an excess of obstetric complications in their early developmental histories, and such complications are associated with a younger age at onset of their disease. Though the data are not conclusive, they also suggest that obstetric complications may be secondary to yet earlier events.

Adult↗