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Biomedical subjects

S Jackson

Publications and source records attributed to S Jackson.

At least 163 records · Page 9Linked to original sources
PubMed1997

Characterisation of carnitine palmitoyltransferases in patients with a carnitine palmitoyltransferase deficiency: implications for diagnosis and therapy.

OBJECTIVES: Carnitine palmitoyltransferase (CPT) deficiency is one of the most common defects of mitochondrial fatty acid oxidation. Two different enzymes (CPT-I and CPT-II) are involved. Due to problems in measuring enzyme activity, relatively little is known about the substrate specificity of each of the human enzymes. This is of considerable importance in the treatment of patients. The objectives were to establish a reliable method for the measurement of CPT activity in whole cells, to use this to characterise the substrate specificity of each enzyme, and finally, to determine if medium chain triglycerides would be of benefit in the treatment of deficient patients. METHODS: A simple permeabilisation technique was used which allows the measurement of CPT activity in a small amount of cultured skin fibroblasts or peripheral blood cells. Using this technique three patients were identified with CPT deficiency. In two of these patients, one with CPT-I deficiency and one with CPT-II deficiency, a complete substrate specificity profile of the mitochondrial carnitine acyltransferases was established for all saturated even chain acyl-CoA esters. RESULTS: For both enzymes the highest CPT activity was with C12-CoA. About 70% of total cellular carnitine octanoyltransferase activity was due to mitochondrial CPT. As CPT is involved in the transport of medium chain fatty acids the metabolic response of a patient with CPT-II deficiency to dietary medium chain triglycerides was assessed. Despite the normal production of ketone bodies there was a significant medium chain dicarboxylic aciduria in the patient, indicating a limited capacity of the CPT independent mitochondrial uptake of medium chain fatty acids. CONCLUSIONS: CPT deficiency can easily be diagnosed in permeabilised cultured skin fibroblasts. Both CPT-I and CPT-II are more active with medium chain length substrates than previously assumed. Care should therefore be taken in the treatment of these patients with medium chain triglycerides.

Adult↗
PubMed1997

Effect of anaerobiosis on cysteine protease regulation during the embryonic-larval transition in

Hydrated encysted embryos of the brine shrimp Artemia franciscana have the ability to withstand years in anaerobic sea water using metabolic strategies that enable them to inactivate all cell metabolic activities and then to resume development when placed in aerobic sea water. However, this unique characteristic of Artemia franciscana embryos is lost during a very short period, at the embryonic­larval transition period of development, coincident with the appearance of prenauplius larvae. Thus, while encysted embryos show complete inhibition of proteolysis over at least 4 years under anoxia, control of this activity, together with resistance to anoxia, is lost in newly hatched nauplius larvae after only a few days in anaerobic sea water. In contrast to encysted embryos, young larvae in anaerobic sea water produce large amounts of lactic acid, which reaches a concentration of nearly 50 mmol l-1 within 12 h of incubation. The accumulated lactic acid is believed to reduce the intracellular pH (pHi) to considerably less than 6.3, the value found in encysted embryos after 5 months in anaerobic sea water. We find that larvae, in contrast to embryos, lose cytoplasmic proteins at the rate of 4­5 ng h-1 larva-1 upon transfer to anaerobic sea water, while yolk proteins are not degraded in either embryos or larvae under anoxic conditions. The decline in cytoplasmic protein levels in anaerobic larvae may be due to activation of an endogenous cysteine protease (CP) as the pHi becomes acidic. Contributing to the apparent uncontrolled CP activity is a decrease in the level of cysteine protease inhibitor (CPI) activity during the embryonic­larval transition period, resulting in an increase in the CP/CPI ratio, from approximately 0.5 in embryos to greater than 1.0 in newly hatched larvae. Finally, data are presented to suggest that loss of the 26 kDa stress protein from embryos during the embryonic­larval transition may also contribute to the loss in resistance of young nauplius larvae of A. franciscana to anaerobic conditions.

Journal Article↗
PubMed1997

[Alkaloids in Sophora alopecuroides seed and relevant tests for activity].

Seven alkaloids were isolated from the seed of Sophora alopecuroides and identified to be oxymatrin, oxysophocarpine, cytisine, matrine, sophocarpine, sophoridine and nicotine respectively by comparing chromactographic and spectral characteristics with authentic known compounds. Nicotine was isolated from Sophora for the first time. The activity of extracts and alkaloids against cancer, virus, dermatophytes and bacteria was carried out in vitro.

Alkaloids↗
PubMed1997

Female urinary incontinence--symptom evaluation and diagnosis.

The assessment of female urinary incontinence aims to evaluate the severity of the patient's condition and its impact on her quality of life. The initial evaluation should include investigation of the patient's symptoms, the compilation of a frequency/volume chart, physical examination and urinalysis. Concurrent confounding conditions should be addressed. For effective treatment, it is necessary to differentiate between urge incontinence secondary to detrusor instability and stress incontinence due to sphincter weakness. Symptom assessment alone, performed clinically or by questionnaire, is diagnostically inaccurate and urodynamic diagnosis is necessary before invasive treatment. Self-reporting of symptom severity does correlate reasonably with objective measures of fluid loss, although standardised methods for the quantification of incontinence should be developed to allow comparisons between patients and the monitoring of disease progression and outcome. Symptom severity does not correspond to patients' perception of the effect of the condition on quality of life and this is an important factor in identifying what treatment is appropriate.

Female↗
PubMed1996

Interleukin-1 beta-converting enzyme-like protease cleaves DNA-dependent protein kinase in cytotoxic T cell killing.

Cytotoxic T cells (CTL) represent the major defense mechanism against the spread of virus infection. It is believed that the pore-forming protein, perforin, facilitates the entry of a series of serine proteases (particularly granzyme B) into the target cell which ultimately leads to DNA fragmentation and apoptosis. We demonstrate here that during CTL-mediated cytolysis the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), an enzyme implicated in the repair of double strand breaks in DNA, is specifically cleaved by an interleukin (IL)-1 beta-converting enzyme (ICE)-like protease. A serine protease inhibitor, 3,4-dichloroisocoumarin (DCl), which is known to block granzyme B activity, inhibited CTL-induced apoptosis and prevented the degradation of DNA-PKcs in cells but failed to prevent the degradation of purified DNA-PKcs by CTL extracts. However, Tyr-Val-Ala-Asp-CH2Cl (YVAD-CMK) and other cysteine protease inhibitors prevented the degradation of purified DNA-PKcs by CTL extracts. Furthermore, incubation of DNA-PKcs with granzyme B did not produce the same cleavage pattern observed in cells undergoing apoptosis and when this substrate was incubated with either CTL extracts or the ICE-like protease, CPP32. Sequence analysis revealed that the cleavage site in DNA-PKcs during CTL killing was the same as that when this substrate was exposed to CPP32. This study demonstrates for the first time that the cleavage of DNA-PKcs in this intact cell system is exclusively due to an ICE-like protease.

Amino Acid Sequence↗
PubMed1996

The role of helix formation in the folding of a fully alpha-helical coiled coil.

To determine when secondary structure forms as two chains coalesce to form an alpha-helical dimer, the folding rates of variants of the coiled coil region of GCN4 were compared. Residues at non-perturbing positions along the exterior length of the helices were substituted one at a time with alanine and glycine to vary helix propensity and therefore dimer stability. For all variants, the bimolecular folding rate remains largely unchanged; the unfolding rate changes to largely account for the change in stability. Thus, contrary to most folding models, widespread helix is not yet formed at the rate-limiting step in the folding pathway. The high-energy transition state is a collapsed form that contains little if any secondary structure, as suggested for the globular protein cytochrome c (Sosnick et al., Proteins 24: 413-426, 1996).

Amino Acid Sequence↗
PubMed1996

Trifunctional enzyme deficiency: adult presentation of a usually fatal beta-oxidation defect.

Disorders of mitochondrial fatty acid oxidation are a common cause of exercise-induced rhabdomyolysis and myoglobinuria. We report three adult patients from a family with symptoms of recurrent exercise-induced rhabdomyolysis. This presentation closely resembles adult-type carnitine palmitoyltransferase II deficiency except that these patients had an associated peripheral neuropathy. Investigation of fatty acid oxidation in the patients revealed a deficiency of the mitochondrial trifunctional enzyme of beta-oxidation, a newly described fatty acid oxidation disorder with multiorgan involvement and a usually fatal outcome in early childhood. Our cases therefore represent a new phenotype of the disease, which is characterized by recurrent rhabdomyolysis and peripheral neuropathy, but without involvement of other organs, and which is associated with prolonged survival beyond the fourth decade. A low-fat/high-carbohydrate diet proved beneficial in one of the patients, drastically reducing the frequency of rhabdomyolytic episodes. Our findings suggest that mitochondrial trifunctional enzyme deficiency should be considered in patients with recurrent episodes of myoglobinuria and peripheral neuropathy presenting in later life.

Adult↗
PubMed1996

Serum and secretory IgA from HIV-infected individuals mediate antibody-dependent cellular cytotoxicity.

The potential function of IgA anti-HIV antibodies in mediation of antibody-dependent cellular cytotoxicity (ADCC) was investigated in this study. Serum IgA isolated from HIV-seropositive subjects in stage B3 or C3 and from healthy seronegative individuals was compared to IgG and whole serum for the ability to mediate ADCC. Peripheral blood mononuclear cells isolated from uninfected donors were used as effectors against CEM-NKr cells chronically infected with the HTLV-IIIB strain of HIV-1. Whole sera, isolated IgA, and IgG from both groups of seropositive individuals were capable of significant ADCC lysis against infected CEM-NKr cells compared to identical preparations from seronegative individuals. In comparing ADCC activity between the two seropositive groups, IgG mediated higher mean ADCC levels in the C3 group at the two highest concentrations of antibody assayed (P < 0.03), whereas IgA mediated the highest mean ADCC levels in the B3 group at all concentrations. Secretory IgA (S-IgA) isolated from colostrum of HIV-infected women was also examined for ADCC capabilities against infected CEM-NKr cells. Significant differences were observed between ADCC mediated by S-IgA from seropositive mothers compared to seronegative mothers (P < 0.04), but the amount of lysis detected was not as great as that seen with serum IgA. The presence of IgG, serum IgA, and secretory IgA antibodies capable of mediating ADCC may be critical in maintaining a functional immune response in all stages of HIV infection.

AIDS-Related Complex↗
PubMed1996

The balance of prevention, investigation, and treatment in the management of child protection services.

The planning, development, and review of child protection services and policies (management) is vitally important and yet to date has received very little consideration. This paper explores the balance between three components of child protection policy: prevention, investigation, and treatment. As part of a review of the management of child protection services in Wales, the authors examined the effectiveness of Area Child Protection Committees (ACPCs), which are multidisciplinary forums responsible for the local provision of child protection services. Thirty-eight (of 171) representatives were interviewed. The balance of the three components (prevention, investigation, and treatment) in policy making was explored. Overall, there was a substantial emphasis on investigation procedures, with very little consideration of prevention strategies, and treatment services virtually ignored. Treatment was described as a "gap" in the service consideration of ACPCs. The authors consider ways to shift the balance so that treatment and prevention services can be given more priority within a comprehensive child protection service.

Child↗
PubMed1996

Attitudes and beliefs within the Sikh community regarding organ donation: a pilot study.

The current shortage of organs for transplantation is a matter of considerable concern in the United Kingdom (U.K.). Whilst issues of histocompatibility create particular problems in this respect for the Asian population in the U.K., it is sometimes suggested that there is also a resistance to the idea of organ transplantation among this community. To explore this issue, a small-scale interview study was conducted in Coventry among members of the Sikh community. A judgemental sample of 22 individuals, from different strata of the local Sikh community, were interviewed either in one-to-one interviews or in a focus group. These interviews had two broad aims: to determine the prevailing attitudes towards organ transplantation, and to gauge the impact and acceptability of the current Department of Health campaign literature. It was found that, whilst there were a number of misgivings to do with notions of mutilation and reincarnation, and anxieties as to technical or clinical aspects of the transplantation process, the prevailing view was supportive of transplantation, and organ donation was seen as a highly appropriate means of exhibiting the altruistic tradition within Sikhism. Such barriers that exist to the idea of transplantation seem to have more to do with knowledge and understanding than with cultural or religious factors. Concerning the campaign literature, informants identified a number of shortcomings, and indicated ways in which the impact of the leaflets and posters might be enhanced. Although the generalizability of these findings is limited, and despite possible threats to the validity of the data collected, this study has produced findings with significant implications for future policy in this area.

Ethnicity↗
PubMed1996

Improved analogs and novel delivery systems for somatostatin octapeptides.

Appropriate N-terminus modification can result in somatostatin (SRIF) octapeptide analogs that are both more potent and more selective in vitro for the human SRIF receptor type 2 (hsst2). In addition, these modifications can improve the duration of action and bioavailability of SRIF analogs following parenteral administration, as shown by both pharmacological and distribution studies in vivo with BIM-23190 and BIM-23197 in the rat.

Amino Acid Sequence↗
PubMed1996

Malaria control and fever management in Henan Province, China, 1992.

Henan Province, which once had the highest malaria prevalence in China, had only 318 reported cases in 1992. Our purpose was to investigate this late 'consolidation phase' of malaria control in Henan with reference to malaria surveillance. We conducted a questionnaire survey of village doctors in Shang Shi Qiao Township during the transmission period of 1992. Of the 732 recorded fever cases, 16 were probable malaria cases by clinical and treatment response criteria, but only one received a full course of antimalarials. Of the 732 patients, 61% had fever every day, 37% went for treatment the first day, 52% waited 2-3 days and 10% waited longer. One hundred and twenty-eight patients took self-medication before seeing the doctor. Blood examination was carried out in 526 (71%) fever cases but only four were positive, all for Plasmodium vivax. Our findings highlight problems relating to patient behaviour and motivation of village doctors, malaria treatment, surveillance and microscopy, rural migration, economic development and malaria transmission. All need to be considered for reforming the malaria control strategy in Henan Province.

Adolescent↗
PubMed1996

The Bristol Female Lower Urinary Tract Symptoms questionnaire: development and psychometric testing.

OBJECTIVE: To develop a questionnaire that is sensitive to changes in the symptomatology of the female lower urinary tract, particularly urinary incontinence, providing an instrument that can characterize symptom severity, impact on quality of life and evaluate treatment outcome. PATIENTS, SUBJECTS AND METHODS: Items covering as wide a range of urinary symptoms as possible were devised after consultation with clinicians and a health scientist, a literature review and discussion with patients. Additional items assessed the degree of 'bother' that symptoms were causing. Eighty-five women with clinical symptoms attending for urodynamic assessment and 20 women with none were asked to self-complete the questionnaire. The instrument's validity was assessed by interviewing patients and measuring levels of missing data, comparing symptom scores between clinical and non-clinical populations and comparison with frequency/volume charts and data from pad tests. The instrument's reliability was assessed by measuring both internal consistency and stability, using a 2-week test-retest analysis. RESULTS: The questionnaire was completed by the patients with a mean of only 2% of items missing; most questions were easily understood. Construct validity was good, with the instrument easily differentiating clinical and non-clinical populations. Criterion validity, as tested against frequency/volume charts and pad-test data, was acceptable, with Kappa coefficients of 0.29-0.79 for frequency/volume data and Spearman rank correlations of 0.50-0.97 and 0.31-0.67 for frequency/volume and pad-test data, respectively. The reliability of the instrument was good; a Cronbach's alpha of 0.78 indicated that the symptom questions had high internal consistency, while stability was excellent, with 78% of symptoms and problems answered identically on two occasions, and Spearman rank correlations of 0.86 and 0.90, respectively. CONCLUSION: The instrument has good psychometric validity and reliability. The stability demonstrated at baseline and the ability to differentiate clearly between community and clinical populations suggest that it should be ideal for measuring changes following therapeutic intervention. The addition of life-impact items and a 'bother' factor may provide the opportunity to identify those women who wish treatment for their symptoms; this dimension requires further exploration.

Adult↗
PubMed1996

Planar imaging quantification using 3D attenuation correction data and Monte Carlo simulated buildup factors.

A new method to correct for attenuation and the buildup of scatter in planar imaging quantification is presented. The method is based on the combined use of 3D density information provided by computed tomography to correct for attenuation and the application of Monte Carlo simulated buildup factors to correct for buildup in the projection pixels. CT and nuclear medicine images were obtained for a purpose-built nonhomogeneous phantom that models the human anatomy in the thoracic and abdominal regions. The CT transverse slices of the phantom were converted to a set of consecutive density maps. An algorithm was developed that projects the 3D information contained in the set of density maps to create opposing pairs of accurate 2D correction maps that were subsequently applied to planar images acquired from a dual-head gamma camera. A comparison of results obtained by the new method and the geometric mean approach based on published techniques is presented for some of the source arrangements used. Excellent results were obtained for various source-phantom configurations used to evaluate the method. Activity quantification of a line source at most locations in the nonhomogeneous phantom produced errors of less than 2%. Additionally, knowledge of the actual source depth is not required for accurate activity quantification. Quantification of volume sources placed in foam, Perspex and aluminium produced errors of less than 7% for the abdominal and thoracic configurations of the phantom.

Biophysical Phenomena↗
PubMed1996

Kinship care: the African American response to family preservation.

The number of children entering the foster care system is increasing at an alarming rate. The increase in children entering foster care, compounded by political, economic, and social factors, has created a phenomenon in the African American community--formal kinship care. Formal kinship care is defined as a system through which the state or county has custody of the child but a relative takes care of the child. This article discusses increased kinship care as a resilient response by the African American community. The strengths and resilience of the African American family can be attributed in part to a strong kinship network. In this manner, the African American community is preserving the family. This community clearly needs support through imaginative social work policies and practice.

Black or African American↗
PubMed1996

The admission of Asian patients to intensive therapy units and its implications for kidney donation: a preliminary report from Coventry, UK.

OBJECTIVE: To determine the relative admission rates of Asian and non-Asian patients to intensive therapy units (ITUs) in Coventry and to explore the implications of these rates for the transplantation of organs to Asian people. DESIGN: Examination of 1991 census data and a retrospective review of ITU admissions books. Data were collected on ethnic background, presenting diagnosis, and clinical outcome for each admission. SETTING: The three ITUs in Coventry. PATIENTS: All admissions to the ITUs from 1990-93 inclusive. RESULTS: Asian patients were admitted to ITUs disproportionately to their numbers in the Coventry population. Members of the Asian community were less than half as likely to be admitted to an ITU (p < 0.001) and more likely to die while there (p = 0.007) than members of the non-Asian population in Coventry. The proportions of patients referred to the transplant unit and the rates of subsequent donation do not seem to differ significantly for Asian and non-Asian patients (p = 0.26 in both cases). CONCLUSIONS: There are clear implications for the availability of cadaveric kidney transplantation to Asian patients, given that few kidneys from non-Asian donors are histocompatible with Asian recipients. Indeed, in Asians, promotion of living related donation may be more effective in countering the organ shortfall than efforts to increase consent to cadaveric transplantation. However, it may be valuable to investigate any patterns of morbidity or social or cultural factors that might explain the initial low admissions rates to ITUs for Asian patients.

Asia↗