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Biomedical subjects

L Pearl

Publications and source records attributed to L Pearl.

At least 19 recordsLinked to original sources
PubMed1995

The structural basis of specific base-excision repair by uracil-DNA glycosylase.

The 1.75-A crystal structure of the uracil-DNA glycosylase from herpes simplex virus type-1 reveals a new fold, distantly related to dinucleotide-binding proteins. Complexes with a trideoxynucleotide, and with uracil, define the DNA-binding site and allow a detailed understanding of the exquisitely specific recognition of uracil in DNA. The overall structure suggests binding models for elongated single- and double-stranded DNA substrates. Conserved residues close to the uracil-binding site suggest a catalytic mechanism for hydrolytic base excision.

Amino Acid Sequence↗
PubMed1995

Knowledge and experience of young people regarding drug misuse, 1969-94.

OBJECTIVE: To monitor young people's knowledge and experience of illicit drugs between 1969 and 1994 at intervals of five years. DESIGN: The same anonymously completed questionnaire was used throughout. SETTING: Three Wolverhampton secondary schools representing three different socioeconomic groups. SUBJECTS: 392 pupils aged 14 to 15 completed the questionnaire in 1994. Previous sample sizes were 471 in 1969, 523 in 1974, 648 in 1979, 540 in 1984, and 380 in 1989. MAIN OUTCOME MEASURES: Self reported levels of knowledge and experience of illicit drugs. RESULTS: Over 25 years the proportion of pupils who knew someone taking drugs more than quadrupled from 15% (71/471) to 65% (254/392), and the proportion who had been offered drugs increased ninefold from 5% (24) to 45% (175). Both of these proportions more than doubled over the past five years. In 1994 the proportions of pupils mentioning "ecstasy" (methylenedioxymethamphetamine), amphetamines, and crack cocaine increased significantly (P < 0.01) and the proportion mentioning opiates decreased significantly (P < 0.01). "Poppers" (amyl nitrite) were mentioned for the first time. "To feel big, to show off, look grown up" has continued to be the main perceived reason for taking drugs. Television has continued to be the main source of information. CONCLUSIONS: In the past five years in particular young people's exposure to illicit drugs has increased dramatically. Despite more education about drugs, pupil's knowledge remains limited. Social pressures remain the first perceived reason for taking drugs. The media have a responsibility not to glamorise drugs.

Adolescent↗
PubMed1995

Absence of an association between G-CSF support and clinical response in heavily pre-treated ovarian cancer patients receiving salvage chemotherapy with paclitaxel (Taxol).

This study was undertaken to determine if there was an association between the use of granulocyte colony-stimulating factor (G-CSF) and the clinical response to paclitaxel in patients with advanced ovarian cancer. Seventy-seven heavily pre-treated patients were given 135 mg/m2 paclitaxel every 21 days, with G-CSF support as necessary according to standard criteria. Patients were stratified into two subgroups according to the presence or absence of G-CSF use. The clinical response, progression-free interval (PFI) and survival were determined for each patient and analyzed relative to G-CSF use. Thirty-three patients received G-CSF support. The overall response rate was 32% (one complete and 24 partial) with similar patient numbers from each subgroup. The mean PFI and survival were not significantly different between the subgroups; 170.9 +/- 21.2 and 401 +/- 45.5 days (G-CSF) and 182.4 +/- 30.2 and 367 +/- 36 days (no G-CSF), respectively. We conclude that G-CSF use is not associated with response to paclitaxel in heavily pre-treated ovarian cancer patients.

Adult↗
PubMed1994

Crystal structure of AmiC: the controller of transcription antitermination in the amidase operon of Pseudomonas aeruginosa.

The crystal structure for the negative regulator (AmiC) of the amidase operon from Pseudomonas aeruginosa has been solved at a resolution of 2.1 A. AmiC is the amide sensor protein in the amidase operon and regulates the activity of the transcription antitermination factor AmiR, which in turn regulates amidase expression. The AmiC structure consists of two domains with an alternating beta-alpha-beta topology. The two domains are separated by a central cleft and the amide binding site is positioned in this cleft at the interface of the domains. The overall fold for AmiC is extremely similar to that for the leucine-isoleucine-valine binding protein (LivJ) of Escherichia coli despite only 17% sequence identity, however, the two domains of AmiC are substantially closed compared with LivJ. The closed structure of AmiC is stabilized significantly by the bound acetamide, suggesting a molecular mechanism for the process of amide induction. The amide binding site is extremely specific for acetamide and would not allow a closed conformation in the presence of the anti-inducer molecule butyramide.

Amidohydrolases↗
PubMed1992

Molecular dynamics of alkylated DNA.

The effect of methylation of the O4 atom of thymine in two oligonucleotide sequences is investigated by molecular dynamics simulations. Three types of environments are considered including: (i) in vacuo calculation, with a distance-dependent dielectric function and unhydrated counter-ions; (ii) in vacuo calculation, with a distance-dependent dielectric constant and hydrated counter-ions; and (iii) with a 9 A thick explicit water layer and counter-ions. In all environments, the oligonucleotide sequence containing the chemically modified thymine paired with guanine is more stable than the oligonucleotide sequence in which the modified thymine is paired with adenine. The methyl group attached to the O4 atom of thymine is found in a syn configuration with respect to the N3 atom. The best fit between the experimental NMR results and the molecular dynamics simulations is obtained using the environment with hydrated counter-ions.

Alkylation↗
PubMed1990

Knowledge and experience of young people regarding drug abuse, 1969-89.

OBJECTIVE: To establish a baseline of knowledge to plan an effective health education programme in schools. The survey was repeated at five year intervals from 1969 to 1989. DESIGN: To preserve consistency, the same anonymous questionnaire, which was confidential to the research workers, was used throughout. SETTING: Three secondary schools in Wolverhampton in different parts of the town and representing different social groups. SUBJECTS: Sample sizes ranged from 471 fourth year pupils (aged 14 to 15) in 1969 to 540 in 1984 and 380 in 1989, the decrease being due mainly to the falling birth rate. There were slightly more girls than boys, and the pupils covered the whole range of academic ability. RESULTS: Over the 20 years the proportion of pupils who knew someone taking drugs more than doubled from 15% (71) to 31% (117) and the proportion who had been offered drugs almost quadrupled from 5% (24) to 19% (72). The changes taking place over the past five years were characterised by an increased knowledge about drugs and the first mention of "crack," a purified form of cocaine, and "ecstasy" (methylenedioxymethamphetamine). Peer influence continued to be given as the prime reason for taking drugs. Over the 20 years, though less often mentioned in 1989, television and newspapers remained the most common source of information. CONCLUSIONS: These results suggest the need for responsible coverage by the mass media and for more effective health and social education programmes to prevent the spread of drug misuse.

Adolescent↗
PubMed1989

Power frequency magnetic field; depressive illness and myocardial infarction.

Surveys were made to determine whether susceptibility to depressive illness and to myocardial infarction of people living in Wolverhampton was related to the intensity of 50 Hz magnetic field outside their homes. Comparing case with control addresses it was found that the field strength was significantly higher for depressive illness (P = 0.033) but not for myocardial infarction.

Depressive Disorder↗
PubMed1986

Knowledge and experience of young people of drug abuse 1969-84.

An anonymous questionnaire survey of the knowledge and experience of drug abuse among fourth year pupils in three Wolverhampton secondary schools in 1969, 1974, 1979, and 1984 showed familiarity with the names of drugs but considerable ignorance and misunderstanding about how the drugs were taken and their dangers. The proportion of pupils who knew someone taking illicit drugs almost doubled over the period from 15% in 1969 to 28% in 1984, and the proportion of those who had been offered illicit drugs almost trebled, from 5% in 1969 to 14% in 1984. Television remained the most important source of information about drugs. Peer group and social pressures continued to be the most important reason for starting to take drugs. The results of this study endorse the need for continued evaluation of programmes of education about drugs. Such programmes must be part of a wider programme of health and social education, define clear goals, and be sensitive to culture, locality, and ability.

Adolescent↗
PubMed1986

Rehabilitative neurosurgery.

The neurosurgical role in rehabilitation rehabilitation was studied. Over a 5-year period, 850 individuals were referred to a rehabilitation center after initial acute care. Surgery was indicated for 66 patients. There were 28 quadriplegic or paraplegic individuals with intractable spasticity. Percutaneous radiofrequency foramenal rhizotomies were found to be 98% effective in relieving posttraumatic spasticity. In 14 patients with cognitive impairment, intellectual improvement had reached a plateau level. These persons underwent computed tomography scanning and cisternography, revealing significant communicating hydrocephalus. After surgical shunt therapy, cognitive improvement was noted in 86%. Nineteen individuals were sent for rehabilitation following spine fracture or progressive quadriplegia; 17 were found to have persistent spinal instability requiring surgical stabilization by fusion. This was successful in all cases without complications. Two persons required decompressive spinal operations, resulting in neurological stabilization or improvement. Five patients developed pain, spasticity, ascending neurological deficit, or autonomic dysreflexia due to posttraumatic syrinx. These symptoms were stabilized or improved following syringosubarachnoid shunting. The authors submit that comprehensive neurosurgical reevaluation is desirable in patients received for rehabilitation. Periodic neurosurgical follow-up is recommended. The neurosurgeon's role is not limited to the acute process.

Brain Diseases↗
PubMed1984

The active site of aspartic proteinases.

The active site of the aspartic proteinase, endothiapepsin, has been defined by X-ray analysis and restrained least-squares refinement at 2.1 A resolution with a crystallographic agreement value of 0.16. The environments of the two catalytically important aspartyl groups are remarkably similar and the contributions of the NH2- and COOH-terminal domains to the catalytic centre are related by a local 2-fold axis. The carboxylates of the aspartyls share a hydrogen bond and have equivalent contacts to a bound water molecule or hydroxonium ion lying on the local diad. The main chains around 32 and 215 are connected by a novel interaction involving diad-related threonines. It is suggested that the two pKa values of the active site aspartyls arise from a structure not unlike that in maleic acid with a hydrogen-bonded intermediate species and a dicarboxylate characterised by electrostatic repulsions between the two negatively charged groups.

Amino Acid Sequence↗
PubMed1983

Percutaneous radiofrequency foramenal rhizotomies.

Thirty quadriplegic and paraplegic patients with intractable spasticity underwent percutaneous radiofrequency foramenal rhizotomies. This produced improvement in 94% of the patients, with excellent results in 73%. The complication rate was 3%. The major disadvantage of the procedure was recurrent spasticity, which was dealt with by simple repetition of the procedure. Rehabilitative goals were facilitated; needless painful disability was avoided; a need for intense nursing was reduced; the prevention and treatment of decubitus ulcer formation was enhanced. The study suggests that this procedure is effective, inexpensive, and at low risk to the patient.

Aged↗
PubMed1983

Spinal hemangiomas.

Three new cases of spinal cord compression due to vertebral hemangioma are reported. The clinical presentation, with spinal pain, radicular radiation, and paraparesis, is similar to that of primary lymphoma, metastatic tumor, and disc disease. If the characteristic plain film changes of vertical trabeculations and striations are present, the preoperative diagnosis is facilitated, but in the majority of cases these are not seen. In some instances, vertebral body or pedicle erosion is present. A myelographic epidural block will be seen on further study. Spinal arteriography can prove helpful. Surgical decompression results in marked neurological improvement if intervention takes place before the onset of complete paralysis. The authors recommend that the diagnosis of vertebral hemangioma be considered in the differential diagnosis of epidural spinal cord compression whenever considered in the differential diagnosis of epidural spinal cord compression whenever a primary malignant neoplasm cannot be identified.

Aged↗
PubMed1981

Knowledge and experience of young people regarding drug abuse between 1969 and 1979.

A trend survey carried out by anonymous questionnaire of the knowledge and experience of drug abuse among fourth-year pupils in three Wolverhampton secondary schools in 1969, 1974, and 1979 showed familiarity with the names of drugs, but that there continues to be considerable ignorance and misunderstanding about how drugs are taken and their dangers. Contact with drugs and drug-taking increased over the first five years, but this trend was not continued through to 1979. Television remained the most important source of information about drugs, while peer group and social pressures remained the most important reason for starting to take drugs. Effective preventive measures must include a health education programme that discusses decision-making processes and a wider view of "drugs in society".

Adolescent↗