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Biomedical subjects

T Gibson

Publications and source records attributed to T Gibson.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

Zinc finger-DNA recognition: analysis of base specificity by site-directed mutagenesis.

Zinc fingers of the Cys2/His2 class are conserved 28-30 amino acid motifs that constitute an important and widespread family of eukaryotic DNA-binding domains. It is therefore of great interest to understand the rules that govern specific recognition of DNA by zinc fingers. The DNA-binding domain of the transcription factor Krox-20 consists of three zinc fingers, each of them making its primary contacts with a three-base pair subsite. We have performed a data base-guided site-directed mutagenesis analysis of Krox-20: nine derivatives were generated, in which one to three amino acid changes had been introduced within finger 2, at positions which were likely to affect the specificity of DNA recognition. The affinities of the different proteins for a panel of potential DNA binding sites were estimated by gel retardation assay. Six of the derivatives bound specific targets with affinities comparable to that of wild type Krox-20 for its consensus binding site. However, the specificity of recognition was dramatically modified at the expected bases, in a manner that could be explained by examining the newly introduced amino acids within the context of the overall finger/triplet interaction. These data provide new insights into the details of zinc finger-DNA interactions and, combined with the modular nature of zinc fingers, illustrate both the potential and the difficulties of utilising these motifs for designing DNA-binding proteins with novel specificities.

Amino Acid Sequence↗
PubMed1992

SH3--an abundant protein domain in search of a function.

Src-homology 3 is a small protein domain of about 60 amino acid residues. It is probably made of beta-sheets. SH3 is present in a large number of eukaryotic proteins which are involved in signal transduction, cell polarization and membrane-cytoskeleton interactions. Here we review its occurrence and discuss possible functions of this domain.

Amino Acid Sequence↗
PubMed1992

Osteoporosis and chronic back pain: a study with single-photon emission computed tomography bone scintigraphy.

A group of 26 patients aged 47-81 years (average 67) with spinal osteoporosis and back pain for more than 6 months were investigated with planar and SPECT bone scintigraphy and anterior and lateral x-rays of the thoracolumbar spine. Abnormal activity on bone scintigraphy was found in all patients, of whom 22 had multiple lesions. A total of 17 (65%) patients had abnormal activity associated with collapsed vertebral bodies, 5 (19%) had degenerative disk disease, and 21 (81%) had facetal joint disease. Of 112 lesions identified by SPECT, 60 (54%) were localized to the apophyseal joints. Facetal lesions were commoner in those patients with more collapsed vertebrae, and 32 facetal lesions (54%) were associated with collapse of the vertebra immediately above or below. Bone scintigraphy findings suggest that in some individuals with osteoporosis and chronic back pain, collapse of the vertebral body or degenerative disk disease are causes of pain. However, the high frequency of increased apophyseal joint activity suggests that the facet joint may also be an important site of origin of pain in these individuals. Bone scintigraphy may identify a subgroup of osteoporotic patients with chronic back pain who would benefit from treatment to the facet joints.

Aged↗
PubMed1992

Renal handling of enalaprilat.

Most converting enzyme inhibitors share a predominantly renal dual elimination pathway consisting of glomerular filtration and tubular secretion. Since enalaprilat has two functional acidic groups, it is likely that it may be secreted via the proximal tubule organic acid system and, thus, its clearances would exceed that of glomerular filtration rate markers. We therefore examined the renal clearance of enalaprilat in normal volunteers and compared it with simultaneously measured inulin and creatinine clearances to explore the contribution of tubular secretion to the renal elimination of the drug. Twelve healthy male subjects with an age range of 24 to 58 years (mean +/- SE, 33.1 +/- 2.8) were studied. They had representative height (178.6 +/- 1.99 cm) and weight (73.3 +/- 2.1 kg) and had normal renal function as judged by blood urea nitrogen (BUN) (6 +/- 0.3 mmol/L [17 +/- 0.8 mg/dL]), plasma creatinine (88 +/- 3 mumol/L [1.0 +/- 0.03 mg/dL]), and creatinine clearance determined by a prestudy 24-hour urine collection (123.2 +/- 6.2 mL/min). Results are as follows: mean creatinine clearance, 2.12 mL/s (127 mL/min); mean inulin clearance, 119.1 ml/min mean creatinine clearance/inulin clearance, 1.07 mean enalaprilat protein binding, 37.9% unbound enalaprilat clearance, 222.4 ml/min; and the mean fractional enalaprilat clearances were: enalaprilat clearance/creatinine clearance, 1.72 (P less than 0.05, difference from 1.0); enalaprilat clearance/inulin clearance, 1.85, (P less than 0.05, difference from 1.0). Our results demonstrate that the clearance of free enalaprilat exceeds that of inulin and creatinine, suggesting that elimination of the drug proceeds through two complementary pathways, namely glomerular filtration and tubular secretion.

Adult↗
PubMed1992

Treatment of Paget's disease by weekly infusions of 3-aminohydroxypropylidene-1,1-bisphosphonate (APD).

Thirty patients with symptomatic Paget's disease of bone were treated with weekly infusions of 30 mg APD for 6 weeks and followed for up to 3 years (mean 2 years). Bone pain diminished or disappeared in 83%. Six months following treatment the serum alkaline phosphatase (sAP) had normalized in 53% and had fallen by an average of 68% in the remainder. The average fall in sAP was 65% at 6 months, 59% at 1 year and 51% at 2 years. Urine hydroxyproline/creatinine ratios (OHp/Cr) fell by an average of 72% over the 6 weeks of treatment whilst serum bone gla protein (BGP) showed no significant change. However, there was a significant fall in the mean BGP of 25% by 6 months following treatment. Radionuclide bone scan abnormalities improved in all patients and showed complete resolution in two. The same regimen was used to retreat eight patients with a persistence or recurrence of symptoms after 1 year. At 6 months following retreatment the sAP had fallen to normal in four and in the remainder by an average of 39%. Two patients had a third course after a further year and by 6 months the sAP had fallen by an average of 50%. Normalization of sAP occurred in 86% of patients with a pretreatment sAP less than 900 iu/l (normal less than 300) and 89% of patients with a sAP less than 600 iu/l immediately following the course of treatment. Therefore, knowledge of the pretreatment and post-treatment sAP should enable prediction of the need for further therapy in most cases. We confirm that APD is an effective and well tolerated treatment for the management of Paget's disease, giving long-term suppression.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

The identification of spinal pathology in chronic low back pain using single photon emission computed tomography.

Bone scintigraphy with single photon emission computed tomography (SPECT) offers improved lesion detection and localization when compared to conventional planar imaging. The SPECT findings were investigated in 80 consecutive patients (aged 18-70 years, median 44) referred to a rheumatology outpatient clinic with low back pain persisting for more than 3 months. Lesions of the lumbar spine were demonstrated in 60% of patients using SPECT but in only 35% with planar imaging. Fifty-one per cent of all lesions were only detected by SPECT, and lesions visualized on SPECT could be precisely localized to the vertebral body, or different parts of the posterior elements. Fifty per cent of lesions involved the facetal joints of which almost 60% were identified on SPECT alone. X-rays of the lumbar spine, with posterior oblique views, failed to demonstrate abnormalities corresponding to almost all SPECT posterior element lesions although it identified abnormalities corresponding to over 60% of anterior SPECT lesions. Computed tomography (CT) was performed in 30 patients with a SPECT lesion and sites of facetal joint activity corresponded to facetal osteoarthritis in 82%. It is concluded that bone scintigraphy with SPECT in patients with chronic low back pain demonstrates many lesions not seen with either X-ray or conventional planar imaging. In addition anatomical localization is greatly enhanced with bone SPECT. The technique offers improved diagnosis in a group of patients often difficult to evaluate, and in particular a means of detecting apophyseal joint pathology which may be responsive to treatment.

Adult↗
PubMed1992

Chronic low back pain: comparison of bone SPECT with radiography and CT.

In patients with chronic low back pain, bone scintigraphy with single photon emission computed tomography (SPECT) of the lumbar spine allows identification of lesions not seen with planar imaging. In this study, findings from radiography, computed tomography (CT), and bone scintigraphy with SPECT in 34 patients with chronic back pain were examined to determine the nature and clinical relevance of the lesions. Twenty-seven patients had lesions at SPECT, of whom 24 (89%) had abnormalities at CT and 18 (67%) had abnormalities at radiography. SPECT allowed identification of 54 lesions, of which only 20 (37%) were detected with planar imaging. Forty-three (80%) SPECT lesions were located at the site of an abnormality also seen at CT and 20 (37%) at the site of an abnormality also seen at radiography. It was concluded that bone SPECT provides diagnostic information in chronic low back pain that is not available with radiography or planar imaging. The majority of lesions seen at SPECT corresponded to identifiable disease at CT.

Adult↗
PubMed1992

Bone scintigraphy following intravenous pamidronate for Paget's disease of bone.

Pamidronate is one of several powerful bisphosphonates able to produce prolonged remissions of Paget's disease. This study examined to what extent bone scan changes parallel the clinical response and whether there is variability in the behavior of individual lesions. Twenty-five patients with pagetic bone pain for more than 2 yr were examined with bone scintigraphy before and on average 8 mo after six 30-mg infusions of pamidronate given weekly. Serum alkaline phosphatase and urinary hydroxyproline-to-creatinine ratios were measured before and 6 mo after treatment. A second course of pamidronate was given to 13 patients who had clinical or biochemical relapse. Of 136 pagetic lesions, 13 (10%) completely resolved, 90 (65%) improved and 33 (24%) remained unchanged. There was no significant difference in response between bony sites, although less active lesions were more likely to resolve completely. In conclusion pamidronate has a powerful effect on bone scan appearances in Paget's disease. Most lesions improve but complete resolution is uncommon. Less active lesions are more likely to resolve and are less likely to require further therapy.

Alkaline Phosphatase↗
PubMed1992

Serial estimation of interleukin 6 as a measure of systemic disease in rheumatoid arthritis.

Disease activity in rheumatoid arthritis (RA) is frequently associated with a marked acute phase response, thrombocytosis, hypergammaglobulinemia and the presence of rheumatoid factors (RF). Interleukin 6 (IL-6) is a cytokine that stimulates hepatocytes to produce acute phase reactants and B lymphocytes to produce immunoglobulin. We measured serum IL-6 in patients with active RA during induction of intramuscular gold therapy. Levels of IL-6 correlated strongly with the erythrocyte sedimentation rate and RF titers and to a lesser degree with platelet counts. It may, therefore, be responsible for many of the systemic manifestations of RA and its measurement in the serum may be a convenient and reproducible variable for the assessment of disease activity in this very common disease.

Arthritis, Rheumatoid↗
PubMed1991

Evidence that nebulin is a protein-ruler in muscle thin filaments.

Partial amino acid sequence was obtained from the massive myofibrillar protein nebulin. This consists of repeating motifs of about 35 residues and super-repeats of 7 x 35 = 245 residues. The repeat-motifs are likely to be largely alpha-helical and to interact with both actin and tropomyosin in thin filaments. Nebulin from different species was found to vary in size in proportion to filament length. The data are consistent with the proposal that nebulin acts as a protein-ruler to regulate precise thin filament assembly.

Actin Cytoskeleton↗
PubMed1991

Solution structure of the basic region from the transcriptional activator GCN4.

The structure of the basic region (i.e., the region responsible for sequence-specific binding to DNA) of the transcriptional activator GCN4 was studied. Two peptide fragments containing either the basic region alone (residues 240-280) or the basic and the dimerization leucine zipper domains (220-280) were synthesized and investigated by nuclear magnetic resonance and circular dichroic spectroscopy. The basic region in the absence of DNA appears as a mobile flexible segment folded into a loose helix. The helical stability increases upon addition of trifluoroethanol and/or lowering of the temperature. Dimerization via the leucine zipper does not affect the three-dimensional structure of the basic region. Possible consequences for the binding to DNA are discussed.

Amino Acid Sequence↗
PubMed1991

Polychlorinated biphenyl congeners in blood of Wisconsin sport fish consumers.

As part of a study to evaluate the effect of chemical contaminants on Wisconsin sport fish consumers, measurements were made of polychlorinated biphenyl (PCB) congeners in human blood sera. A high resolution gas chromatography procedure was employed, with 13 individual congeners used as standards. Analytical recoveries and precision were greater than 90% and replicates were always within +/- 30%. Total concentrations, obtained by summing quantified congeners, ranged from 0.6 to 27.1 micrograms/L. Conventional packed column PCB analysis, conducted on a subset of samples, gave higher total PCB results. On a congener specific basis, congeners 153 (245-245), 138 (234-245), 180 (2345-245) and 118 (245-34) were found most often. These congeners have been reported to be prominent in other matrices. Of the congeners found, 118, 138, and possibly 180 are potentially the most toxic (based on current toxicological information).

Animals↗
PubMed1991

The solution structure of a leucine-zipper motif peptide.

We report the complete structure determination of a 34 residue synthetic peptide with the amino acid sequence of the dimerization domain (leucine zipper) of GCN4. A high resolution structure in solution was obtained by 1H-NMR studies and distance geometry calculations followed by restrained energy minimization. A set of 20 final structures was obtained with an average root mean square deviation of 1.3 A for the backbone atoms (excluding the first and the last two residues). The structure contains an uninterrupted helix. A comparison with a structure previously determined for a larger peptide containing both the DNA-binding region (basic region) and the leucine-zipper motif shows the structural independence of the leucine-zipper domain from the contiguous DNA binding region.

Amino Acid Sequence↗
PubMed1991

Local injection treatment of tennis elbow--hydrocortisone, triamcinolone and lignocaine compared.

Corticosteroid injections are the mainstay of treating tennis elbow even though their effectiveness has not been well established by controlled studies. A survey of consultant rheumatologists confirmed a widespread preference for this treatment but they varied in their choice of steroid dose and preparation. We examined the value of some practices by comparing local injections of 2 ml 1% lignocaine with either 10 mg triamcinolone or 25 mg hydrocortisone made up to 2 ml with 1% lignocaine (Study 1). The investigation was conducted double blind. Within the first 8 weeks, pain relief was greater for triamcinolone than hydrocortisone although the differences were not statistically significant. The response to both steroid preparations was significantly better than for lignocaine up to this point but at 24 weeks, the degrees of improvement were similar for all three groups and many patients still had pain. Relapse was common. In a separate but similarly designed study, triamcinolone 10 mg was compared with 20 mg of the same agent. Improvements of pain were similar and followed the same time scale. Post-injection worsening of pain occurred in approximately half of all steroid treated patients in both studies and this was sometimes severe and persistent. It was less frequent amongst those given lignocaine alone. Skin atrophy was reported in all groups but was more frequent amongst those given triamcinolone in Study 1. In conclusion, more rapid relief of symptoms was achieved with 10 mg triamcinolone than with 25 mg hydrocortisone or lignocaine alone and there was less needed to repeat injections. Results obtained with 20 mg triamcinolone were similar to those of the smaller dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Isolated ACTH deficiency presenting with bilateral frozen shoulder.

We describe a 55-year-old female who presented with a 1-year history of tiredness, depression and painful stiff joints. The most striking clinical abnormality was bilateral frozen shoulders, local corticosteroid treatment of which provided the first diagnostic clue. She was found to have profound diminution of plasma cortisol secondary to an isolated deficiency of ACTH. There was no obvious cause for this. Steroid replacement eradicated her lethargy within 3 months and evidence of frozen shoulders resolved completely.

Adrenal Cortex Hormones↗