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Biomedical subjects

P Lamb

Publications and source records attributed to P Lamb.

At least 19 recordsLinked to original sources

Spontaneous clostridial myonecrosis.

Spontaneous, nontraumatic clostridial myonecrosis is a rare infection with an insidious onset and usually fatal outcome. Spontaneous clostridial myonecrosis has a frequent association with colon carcinoma, leukemia, diabetes mellitus, and drug-induced immunosuppression. We present the case of a 73-year-old diabetic man who died of spontaneous Clostridium septicum myonecrosis, who had presented with fulminant gangrene of the right thigh. Clostridium septicum was cultured from the quadriceps muscle postmortem. At autopsy, in addition to the gangrene, there was a Duke's A adenocarcinoma of the cecum, which had not been diagnosed during life. When spontaneous nontraumatic clostridial myonecrosis is diagnosed at autopsy, investigation should include through exam and the obtaining of past medical history in order to elucidate predisposing factors.

Adenocarcinoma

Evaluation of a commercial measles virus immunoglobulin M enzyme immunoassay.

Paired serum samples from 93 patients suspected of having measles were assayed for measles virus-specific immunoglobulin M (IgM) antibodies by an enzyme immunoassay (EIA), and the results were compared with results from a complement fixation assay and an EIA for measles virus IgG. By using significant serologic rises as the standard for comparison, the IgM EIA assay had a sensitivity of 85.7%, a specificity of 81.3%, a positive predictive value of 95.7%, and a negative predictive value of 54.2%. This assay can be expected to perform well in outbreak situations.

Complement Fixation Tests

Influence of racial origin on admission rates of patients with suspected myocardial infarction in Birmingham.

All patients with suspected myocardial infarction admitted to hospital in four Birmingham health districts were studied to test the hypothesis that Asian patients would be overrepresented and Caribbean patients underrepresented compared with the indigenous population. One thousand four hundred and ninety six patients had a final diagnosis of myocardial infarction or severe angina pectoris. The relative risk of admission for Asian men compared with white men aged 45-64 years was 2.65 (95% confidence interval 2.20 to 3.19) and the risk for Asian men was high for both myocardial infarction and ischaemia when analysed separately. The relative risk of admission for Caribbean men compared with white men was 0.53 (95% CI 0.33 to 1.20). The relative risk for Asian women compared with white women in the same age group was 2.58 (95% CI 1.68 to 3.96), but this was due to an excess of admissions diagnosed as ischaemia rather than infarction in the Asian women. For Caribbean and white women the risk of admission was the same, although significantly fewer Caribbean women were admitted with myocardial infarction. The study was undertaken in 1986-87 and population data had to be derived from the 1981 census. The resident population changed in those five years and so the results were recalculated making allowances for these changes in the health districts involved. Based on these data the admission rate for Asian men with suspected myocardial infarction aged 45-64 was nearly twice that for white men (1.8): the relative risk of admission for Asian men compared with white men was 2.04 (95% CI 1.53 to 2.18). For Caribbean men the relative risk compared with white men was 0.45 (95% CI 0.29 to 0.71). For Asian women the relative risk of admission calculated from the adjusted census data resemble that in white women aged 45-64 years. The relative risk for admission with coronary heart disease in Asians is higher than expected work; one possible explanation for this is that the Asian population resident in the area under study was larger than estimated. The single major difference in risk factors was the high prevalence of diabetes mellitus in Asians (19.5% compared with 8.3% for white residents) but this did not wholly account for the excess of admissions from the Asian community.

Asia

A factor binding GATAAG confers tissue specificity on the promoter of the human zeta-globin gene.

We describe the characterisation of cis-acting sequences which control the tissue specific expression of the human zeta globin gene. An extensive search for enhancer sequences in the vicinity of this gene proved negative. Instead our data demonstrate that the minimal promoter of the zeta gene is itself tissue specific. Sequences close to and possibly including the -100 CACCC and -70 CCAAT boxes display some erythroid specificity. However the principal tissue specific element is a GATAA sequence at -120 directly adjacent to the minimal promoter. Specific deletion of GATAA reduces zeta promoter activity 5 fold in erythroid but not non-erythroid cells. We also demonstrate that an erythroid specific factor binds to this GATAA sequence. Furthermore this factor forms a complex with the transcription factor CP1 which we show interacts with the zeta CCAAT box. We present evidence that the zeta GATAA binding factor is equivalent to GF1 recently purified and cloned by Tsai et al [1]. The erythroid specific GATAA sequence has been found in the promoters and enhancers of a number of erythroid specific genes. Similarly we show here that the zeta globin gene relies on a GATAA sequence in its promoter to specify its expression in erythroid cells.

Animals

The globin switch at the level of mRNA in the developing mouse.

We have carried out a detailed analysis of the relative amounts of zeta, alpha, beta H1, epsilon y2 and adult beta globin mRNA in different tissues of the mouse embryo from Day 8.5 to Day 17.5 i.e. from the first signs of erythropoiesis until almost the end of gestation (birth is Day 19). Interestingly, we find that the zeta to alpha "switch" occurs 24 hours earlier in yolk sac than it does in fetal liver and that the ratio of zeta to alpha mRNA remains higher in the peripheral blood than in the yolk sac or the fetal liver during the latter half of gestation. In fact, zeta mRNA remains present in peripheral blood until Day 15.5. The switch at the mRNA level appears to mimic that found by others [Popp et al, 1987] at the protein level, at least for peripheral blood. This suggests that regulation is not occurring to any major extent at the translational level. The reiteration of the switch in fetal liver suggests that local environmental factors are involved. We find two switches within the beta cluster; beta H1 is expressed first, then epsilon y2 and lastly the two adult beta globins (beta major and beta minor). The switch from beta H1 to epsilon y2 occurs around Day 11.5 and the switch from epsilon y2 to the adult beta globins occurs around Day 15.5. This means that the pattern of expression of the beta-like globin genes in the mouse is more analogous to that found in the human than was previously thought.

Animals

Primary structure polymorphism at amino acid residue 72 of human p53.

We analyzed p53 cDNA and genomic clones from a variety of normal and transformed cells. Sequence analysis of these clones revealed that amino acid residue 72 can be an arginine, proline, or cysteine. This single codon difference results in electrophoretically distinct forms of human p53 seen in normal and transformed cells.

Amino Acid Sequence

Characterization of the human p53 gene.

Cosmid and lambda clones containing the human p53 gene were isolated and characterized in detail. The gene is 20 kilobases (kb) long and has 11 exons, the first and second exons being separated by an intron of 10 kb. Restriction fragments upstream of sequences known to be within the first identified exon were tested for promoter activity by cloning them in front of the chloramphenicol acetyltransferase gene and transfecting the resulting constructs into HeLa cells. A 0.35-kb DNA fragment was identified that had promoter activity. Results of primer extension experiments indicated that the mRNA cap site falls within this fragment, as expected. Analysis of the sequence upstream of the presumptive cap site indicated that the human p53 promoter may be of an unusual type.

Amino Acid Sequence

Erythrocyte insulin receptors following myocardial infarction in non-diabetic subjects.

To determine whether changes in insulin receptors follow acute myocardial infarction, 10 non-diabetic patients were studied on admission to a coronary care unit and 24 h later. Erythrocyte insulin receptors were 86 (50-406) per cell [median (range)] initially and increased significantly to 203 (73-714). Maximum percent specific binding and 50% inhibition of tracer binding did not change significantly. Decreased receptor number after myocardial infarction may contribute to insulin resistance in the acute phase.

Adult

Transformation associated p53 protein is encoded by a gene on human chromosome 17.

The human gene for the transformation-associated p53 phosphoprotein (P53) was assigned to the short arm of chromosome 17 using human-rodent somatic cell hybrids and Southern filter hybridization of cell hybrid DNA. The filters were hybridized to radiolabeled DNA from a genomic clone which contained P53 nucleotide sequences. Hybridization of the probe to a 2.5-kb human DNA fragment in HindIII-digested DNA was used to identify the human P53 gene.

Animals

Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene.

A cDNA clone for human p53 cellular tumor antigen has been isolated and characterized. This clone contains the complete 3'-untranslated region and most of the open reading frame for the protein. Nucleotide sequence analysis revealed that p53 mRNA contains an Alu repeat in the 3'-untranslated region. Hybridization selection experiments showed this clone was capable of selectively binding p53 mRNA. In vitro translation of SV80 mRNA resulted in the synthesis of two immunoreactive p53 polypeptide species. Northern blot analysis showed that human p53 mRNA was 2.8 kb in length and was present in cell lines containing high and low levels of p53 protein. There appears to be only a single p53 gene in human cells and Southern blot analysis demonstrated no major genomic rearrangements or amplification of the p53 gene in the transformed cell lines examined.

Antigens, Neoplasm

Effect of intravenous insulin infusion on mortality among diabetic patients after myocardial infarction.

A review of the records of 353 diabetic patients after a myocardial infarction confirmed the high mortality associated with the condition. The influence of improved diabetic control achieved by intravenous insulin was assessed in 64 patients and compared with earlier experience in a diabetic control group. The frequency of the major complications of myocardial infarction was unchanged and the death rate in both groups was identical (33%); even the patients with blood glucose concentrations greater than 20 mmol/l on admission failed to benefit. Thus careful control of blood glucose concentrations after myocardial infarction in diabetic patients fails to improve the outcome of this high risk group.

Aged

The cellular protein p53 in human tumours.

Tumour tissue from patients with colorectal and mammary tumours has been assayed for the cellular protein p53 using a specific radioimmune assay. The levels of p53 in normal tissues are not detectable with this assay but a substantial number of the tumours showed detectable p53, i.e. the amounts of this protein were significantly increased, to levels which varied from 0.3% to 10% of that found in simian virus 80 (SV80), an SV40 transformed human fibroblast cell line. Sera from the same patients were also assayed for the presence of anti-p53 antibodies and found to be positive in about 12% of the patients. The presence of increased amounts of p53 is not peculiar to malignant tumours since 4 out of 19 fibroadenomas (benign breast tumours) showed detectable amounts of p53 protein. The DNA from tumours was examined by Southern blotting using a variety of restriction enzymes. The arrangement of the p53 gene was not detectably altered in comparison with that in normal human foetal liver DNA. No alteration was observed which could be correlated with the increased levels of p53 in the positive tumours.

Antigens, Neoplasm

Effect of GL enzyme (a highly purified form of hyaluronidase) on mortality after myocardial infarction.

The influence of intravenous GL enzyme (hyaluronidase) on the outcome of myocardial infarction was assessed in a controlled trial among 483 patients presenting within 6 h of the onset of symptoms. There was a consistent trend towards reduced mortality throughout the period of follow-up among GL enzyme treated patients. When the fate of all patients entering the trial was considered, irrespective of final diagnosis, the reduction in mortality at 6 months (27 of 240 GL enzyme patients, 45 of 243 placebo) was statistically significant (p = 0.025).

Clinical Trials as Topic

A comparison of piribedil, procyclidine and placebo in the control of phenothiazine-induced parkinsonism.

A double-blind, cross-over trial of the effectiveness of piribedil, procyclidine and placebo in the control of parkinsonism induced by fluphenazine decanoate was conducted in sixteen cases of chronic schizophrenia. Procyclidine was shown to be more effective and piribedil less effective than the placebo. Piribedil produced a number of unpleasant effects, including headache, vomiting and malaise.

Chronic Disease

The use of salbutamol in obstetrics.

Sympathomimetic amines have been used with the aim of abolishing uterine contractions. On the basis of results from an in vivo technique for testing the specificity and affinity of the beta2-receptor stimulating agents, salbutamol was used for a clinical trial. Five case histories were selected in order to illustrate the possibility of utilizing salbutamol in emergency cases with the aim of achieving uterine relaxation during the period of time between the admission of the patient and the commencement of delivery by, for example, caesarean section.

Adult