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Biomedical subjects

G Pearce

Publications and source records attributed to G Pearce.

At least 37 records · Page 2Linked to original sources
PubMed1998

Moderate exercise during growth in prepubertal boys: changes in bone mass, size, volumetric density, and bone strength: a controlled prospective study.

Cross-sectional studies of elite athletes suggest that growth is an opportune time for exercise to increase areal bone mineral density (BMD). However, as the exercise undertaken by athletes is beyond the reach of most individuals, these studies provide little basis for making recommendations regarding the role of exercise in musculoskeletal health in the community. To determine whether moderate exercise increases bone mass, size, areal, and volumetric BMD, two socioeconomically equivalent schools were randomly allocated to be the source of an exercise group or controls. Twenty boys (mean age 10.4 years, range 8.4-11.8) allocated to 8 months of 30-minute sessions of weight-bearing physical education lessons three times weekly were compared with 20 controls matched for age, standing and sitting height, weight, and baseline areal BMD. Areal BMD, measured using dual-energy X-ray absorptiometry, increased in both groups at all sites, except at the head and arms. The increase in areal BMD in the exercise group was twice that in controls; lumbar spine (0.61 +/- 0.11 vs. 0.26 +/- 0.09%/month), legs (0.76 +/- 0.07 vs. 0.34 +/- 0.08%/month), and total body (0.32 +/- 0.04 vs. 0.17 +/- 0.06%/month) (all p < 0.05). In the exercise group, femoral midshaft cortical thickness increased by 0.97 +/- 0. 32%/month due to a 0.93 +/- 0.33%/month decrease in endocortical (medullary) diameter (both p < 0.05). There was no periosteal expansion so that volumetric BMD increased by 1.14 +/- 0.33%/month, (p < 0.05). Cortical thickness and volumetric BMD did not change in controls. Femoral midshaft section modulus increased by 2.34 +/- 2. 35 cm3 in the exercise group, and 3.04 +/- 1.14 cm3 in controls (p < 0.05). The growing skeleton is sensitive to exercise. Moderate and readily accessible weight-bearing exercise undertaken before puberty may increase femoral volumetric BMD by increasing cortical thickness. Although endocortical apposition may be a less effective means of increasing bone strength than periosteal apposition, both mechanisms will result in higher cortical thickness that is likely to offset bone fragility conferred by menopause-related and age-related endocortical bone resorption.

Age Determination by Skeleton↗
PubMed1998

Exercise before puberty may confer residual benefits in bone density in adulthood: studies in active prepubertal and retired female gymnasts.

Exercise during growth may contribute to the prevention of osteoporosis by increasing peak bone mineral density (BMD). However, exercise during puberty may be associated with primary amenorrhea and low peak BMD, while exercise after puberty may be associated with secondary amenorrhea and bone loss. As growth before puberty is relatively sex hormone independent, are the prepubertal years the time during which exercise results in higher BMD? Are any benefits retained in adulthood? We measured areal BMD (g/cm2) by dual-energy X-ray absorptiometry in 45 active prepubertal female gymnasts aged 10.4 +/- 0.3 years (mean +/- SEM), 36 retired female gymnasts aged 25.0 +/- 0.9 years, and 50 controls. The results were expressed as a standardized deviation (SD) or Z score adjusted for bone age in prepubertal gymnasts and chronological age in retired gymnasts. In the cross-sectional analyses, areal BMD in the active prepubertal gymnasts was 0.7-1.9 SD higher at the weight-bearing sites than the predicted mean in controls (p < 0.01). The Z scores increased as the duration of training increased (r = 0.32-0.48, p ranging between <0.04 and <0.002). During 12 months, the increase in areal BMD (g/cm2/year) of the total body, spine, and legs in the active prepubertal gymnasts was 30-85% greater than in prepubertal controls (all p < 0.05). In the retired gymnasts, the areal BMD was 0.5-1.5 SD higher than the predicted mean in controls at all sites, except the skull (p ranging between <0.06 and <0.0001). There was no diminution across the 20 years since retirement (mean 8 +/- 1 years), despite the lower frequency and intensity of exercise. The prepubertal years are likely to be an opportune time for exercise to increase bone density. As residual benefits are maintained into adulthood, exercise before puberty may reduce fracture risk after menopause.

Adolescent↗
PubMed1996

Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group.

OBJECTIVE: To compare safety and efficacy of lamivudine-zidovudine combination therapy with zidovudine monotherapy in treating human immunodeficiency virus type 1 (HIV-1)-infected, antiretroviral therapy-naive patients. DESIGN: Double-blind, randomized, multicenter, comparative trial of 129 patients throughout 24 weeks followed by 24 weeks of open-label lamivudine in combination with zidovudine. SETTING: Outpatients from 14 hospitals in Belgium, France, Germany, Spain, and the United Kingdom were enrolled within 6 months. PATIENTS: HIV-1-positive, antiretroviral-naive ( < or = 4 weeks prior zidovudine use) patients aged atleast 18 years with CD4+ cell counts between 0.10 x 10(9)/L and 0.40 x 10(9)/L (100-400/microL). INTERVENTION: Patients received either 300 mg of lamivudine every 12 hours in combination with 200 mg of zidovudine every 8 hours for 24 weeks or zidovudine monotherapy for 24 weeks. All patients were then allowed to receive zidovudine in combination with open-label lamivudine (300 mg every 12 hours). MAIN OUTCOME MEASURES: Efficacy was assessed by changes in CD4+ cell counts beta 2-microglobulin, neopterin, HIV-1 immune-complex dissociated (ICD) p24 antigenemia, and HIV-1 viral load. Safety was assessed by incidence of adverse clinical events and defined laboratory-measured toxic effects. RESULTS: Combination therapy showed superior treatment effects compared with monotherapy during the first 24 weeks as documented by changes in CD4+ cell counts (increase of 0.08 x 10(9)/L vs 0.02 x 10(9)/L; P < .001), ICDp24 (-88% vs -49%; P = .04), cellular viremia (-1.27 vs -0.20 log10 median tissue-culture infected dose [TCID50] per 10(6) peripheral blood mononuclear cells; P = .001), and viral load measured by HIV-1 RNA polymerase chain reaction using a Roche method (-1.33 vs -0.57 log10 copies/mL; P = .001) or an immune-capture method (-0.6 vs -0.14log10 copies/mL; P = .008). Observed changes were sustained to 48 weeks for patients continuing to receive combination therapy. Patients switching to receive combination therapy at week 24 showed improvements in CD4+ cell count and viral load to week 48. Mutation results suggested that mutations associated with zidovudine resistance may have developed more slowly over the first 24 weeks in patients receiving combination therapy. In contrast, mutations associated with lamivudine resistance appeared to develop rapidly, despite sustained antiviral treatment effect. However, the number of patients evaluated for genotypic changes was small, and confirmation of these results is needed in larger studies. No statistically significant differences in incidence or severity of clinically manifested or laboratory-measured toxic effects were noted between treatment groups. CONCLUSIONS: The combination of lamivudine and zidovudine results in a potent and sustained antiviral effect in antiretroviral-naive patients that is superior to that observed with zidovudine monotherapy.

Adult↗
PubMed1996

Homozygous hereditary C1q deficiency and systemic lupus erythematosus. A new family and the molecular basis of C1q deficiency in three families.

OBJECTIVE: To describe a new kindred with Clq deficiency and to identify the molecular lesions responsible for complete functional C1q deficiency in this and 2 other previously described kindreds. METHODS: The A-, B-, and C-chain genes of C1q were amplified by polymerase chain reaction, cloned, and sequenced. The DNA sequence was checked for mutations. RESULT: Patient 1 had a homozygous G-to-A change at codon 6 of the C chain, causing an amino acid change from Gly to Arg. Patient 2 had a homozygous deletion of a C nucleotide at codon 43 of the C-chain, causing a frame shift, leading to a premature stop codon at codon 108. Patient 3 had a homozygous C-to-T mutation at amino acid position 41 of the C chain, resulting in a premature stop codon. CONCLUSION: In the homozygous state, the mutations are sufficient to cause complete deficiency of Clq. The mutation in patient 1 has been previously reported in a patient of different ethnic origin. A survey of a series of 158 DNA samples from patients with systemic lupus erythematosus showed no other examples of this mutant allele.

Base Sequence↗
PubMed1996

Does weight-bearing exercise protect against the effects of exercise-induced oligomenorrhea on bone density?

Does weight-bearing exercise offset bone loss associated with oligomenorrhea? If so, bone mineral density (BMD) will be stable at weight bearing sites but decrease at non-weight-bearing sites with increasing duration of oligomenorrhea. To test this hypothesis, BMD (g/cm2), was measured by dual-energy X-ray absorptiometry in 41 oligomenorrheic ballet dancers aged 17.7 +/- 0.2 years (mean +/- SEM) and 46 age-matched controls with normal menstrual function. BMD correlated negatively with the duration of oligomenorrhea at weight-bearing and non-weight-bearing sites (femoral neck, r = -0.33, p < 0.05; Ward's triangle, r = -0.29, p = 0.06; trochanter, r = -0.33, p < 0.05; lumber spine, r = -0.25, p = 0.1; skull, r = -0.29, p = 0.06; arms, r = -0.32, p < 0.05; ribs, r = -0.30, p = 0.06). The slopes of the regression of BMD on duration of oligomenorrhea were greater at the proximal femur (trochanter, -0.28 +/- 0.13, femoral neck, -0.24 +/- 0.11; Ward's triangle, -0.29 +/- 0.15) than the skull (-0.15 +/- 0.08, p < 0.05, p < 0.1, p < 0.1 respectively). The slopes at the trochanter and femoral neck were also greater than at the ribs (-0.10 +/- 0.05; both p < 0.1). In the dancers with oligomenorrhea of less than 40 months duration, BMD was higher than the age-predicted mean at weight-bearing sites (except the lumber spine), but not at non-weight-bearing sites (femoral neck, 9.1 +/- 3.4%; Ward's triangle, 10.0 +/- 1.7%; trochanter, 9.4 +/- 4.1%, all p < 0.05; lumbar spine, -2.1 +/- 2.7%, NS; skull, -2.5 +/- 2.1%, NS; ribs, -3.0 +/- 1.6% NS; arms, -3.9 +/- 1.6%; p < 0.05). In the dancers with greater than 40 months oligomenorrhea, BMD was no higher than the age predicted mean, at the weight bearing sites, and was lower at non-weight bearing sites (femoral neck, 4.3 +/- 2.3%, NS; Ward's triangle, 3.5 +/- 3.2%, NS; trochanter, 2.1 +/- 2.7%, NS; lumbar spine, -3.8 +/- 2.1%, NS; arms, -7.5 +/- 0.8%, p < 0.05; skull, -6.2 +/- 1.8%, p < 0.01; ribs, -5.4 +/- 1.1%, p < 0.0001). In conclusion, weight-bearing exercise is unlikely to offset the deleterious effects of oligomenorrhea. Bone loss appears to occur at all sites but may begin from a higher level at weight-bearing sites and may proceed more rapidly.

Absorptiometry, Photon↗
PubMed1996

Salmeterol: a study by prescription-event monitoring in a UK cohort of 15,407 patients.

OBJECTIVE: To examine the safety of the long-acting beta2-agonist, salmeterol, in general medical practice in the U.K. DESIGN: In Prescription-Event Monitoring (PEM) the exposure data are derived from prescriptions confidentially provided by the Prescription Pricing Authority. Outcome data are obtained by questionnaires (green forms) on which prescribing medical practitioners recorded event (safety) data. Additional information is obtained from the patients' lifetime clinical records, from follow-up of all pregnancies, and from death certificates. SETTING: PEM provides an observational cohort study in which there is no interference with the medical decision on which drug is prescribed for individual patients. SUBJECTS: A total of 15,407 patients were given salmeterol and observed for a minimum of 1 year. RESULTS: Headache, tremor, and palpitations were associated with the use of salmeterol. No unexpected major adverse events were noted, although in this study there was a total of 1022 deaths. Of these, 73 were due to asthma, but only 39 of these patients were taking salmeterol in the last month of life. All of these deaths appear on careful examination of the clinical records to have been due to natural causes, although in a minority (four, 10%) of the group of 39 subjects, a temporal relationship between death and the use of salmeterol makes it difficult to exclude a possible association. The study suggests that advanced age and severity of disease were the most likely factors contributing to asthma mortality in the population studied. CONCLUSION: Headache, tremor, and palpitations occur as adverse effects of salmeterol and lead to withdrawal of the drug in some subjects. No unexpected adverse reaction has been noted and paradoxical bronchospasm was reported in only three subjects. The study has produced no evidence that salmeterol contributed to death in any of the patients examined.

Adolescent↗
PubMed1996

The safety of finasteride used in benign prostatic hypertrophy: a non-interventional observational cohort study in 14,772 patients.

OBJECTIVE: To examine the safety of finasteride as used in general medical practice to treat benign prostatic hypertrophy (BPH). PATIENTS AND METHODS: Information was collected on 14,772 patients who were included in an observational cohort study conducted using Prescription-Event Monitoring. RESULTS: Finasteride was reported to have been effective in 60% of the patients in whom an opinion on efficacy was recorded. Impotence or ejaculatory failure was reported in 2.1% of the patients, decreased libido in 1% and gynaecomastia and related conditions in 0.4%. Impotence was the most frequent reason for stopping treatment with finasteride and was the most commonly reported adverse reaction to the drug. Of the patients included in the elderly cohort involved in this study, 819 (5.5%) died; none of these deaths was attributed to finasteride. CONCLUSION: Impotence or ejaculatory failure, decreased libido and gynaecomastia in a small proportion of patients were associated with the use of finasteride. The results of this study strongly suggest that this drug is acceptably safe when used in accordance with the current prescribing information.

Adolescent↗
PubMed1996

Virological and immunological analysis of a triple combination pilot study with loviride, lamivudine and zidovudine in HIV-1-infected patients.

OBJECTIVE: To compare two antiretroviral regiments, loviride plus lamivudine (3TC) plus zidovudine (ZDV) (triple combination) and loviride plus ZDV (double combination) in terms of pharmacokinetic interactions, tolerability, safety, and immunological and virological efficacy. STUDY DESIGN: An open, case-controlled, pharmacokinetic and 24-week continuous treatment pilot study. PATIENTS: Twenty p24 antigen-positive patients, 10 per treatment group, were matched according to p24 antigenaemia less or more than 100 pg, CD4 count less or more than 150 x 10-(6)/l, and gender. Eight out of 10 cases and seven out of 10 controls had received previous antiretroviral therapy. RESULTS: No clinically relevant pharmacokinetic interactions were observed. Both treatment combinations were well tolerated. Median absolute and percentage CD4 count increases above baseline were more pronounced in the triple combination arm than in the double combination arm. Median p24-antigen and plasma viraemia level decreases below baseline were more pronounced in the triple combination arm. The M(184)I/V mutation was detected in all plasma samples of triple combination patients examined at week 12. Mutations conferring resistance to loviride and ZDV were found in a significant subset of patients in both treatment arms. CONCLUSIONS: Both combination regimens have an excellent safety/tolerability profile, but a higher level of in vivo efficacy is achieved by the triple combination, despite genotypic changes conferring resistance to one or all of these agents. The conclusions drawn are limited by small population size and the heterogenous pretreatment history. However, they support the validity of and strongly encourage a rationally designed multidrug combination approach to HIV therapy.

Acetamides↗
PubMed1995

Present and future of osteoporosis therapy.

In the 50-year "modern" history of osteoporosis, there have been about 17 antifracture studies with sufficient attention to design to allow inference regarding efficacy. Antivertebral fracture efficacy has been reported with etidronate, estrogen patch, calcitonin, and 1,25-dihydroxyvitamin D. Two studies using fluoride were positive, and two were negative. Hip fractures have been neglected. One study showed efficacy of hip protectors, one showed efficacy of vitamin D and calcium in nursing home dwellers. The source of most hip fractures is the community. One community based antihip fracture efficacy study using annual injections of vitamin D was positive. There have been no antivertebral or antihip fracture studies in men, or in corticosteroid-related osteoporosis in men or women. Lack of independently repeated demonstration of efficacy, small fracture numbers, and data pooling in some of these (the best) studies leave great uncertainty. Estrogen and bisphosphonates appear to be the best options at this time. New data suggest that calcium supplementation is likely to reduce the rate of bone loss and perhaps reduce fracture rates. The challenge is to maintain and restore the constituents of bone mineral density (BMD), that is: to promote periosteal and endosteal bone formation; reduce endosteal bone resorption and cortical porosity; and increase trabecular thickness, number, and connectivity. There are many opportunities, for instance, intermittent parathyroid hormone (PTH) increases bone strength and, with estrogen, may increase connectivity. The anabolic effects of PTH may be partly mediated by IGF-1. IGF-1 increases periosteal, endosteal, and trabecular bone formation, cortical and trabecular width, and trabecular and endocortical connectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗
PubMed1994

Overexpression of the prosystemin gene in transgenic tomato plants generates a systemic signal that constitutively induces proteinase inhibitor synthesis.

Tomato plants (Lycopersicon esculentum, var. Better Boy) were stably transformed with a gene consisting of the open reading frame of a prosystemin cDNA under the regulation of the cauliflower mosaic virus 35S promoter. The leaves of the transgenic plants constitutively produced proteinase inhibitor I and II proteins, which accumulated over time to levels exceeding 1 mg/g of dry leaf weight. This phenotype contrasts with that of untransformed plants, which produce proteinase inhibitor proteins in leaves only in response to wounding or chemical inducers. The transgenic plants were also stunted, although they appeared normal in all other respects. Grafting the upper half (scion) of an untransformed tomato plant onto the lower half (root stock) of a tomato plant expressing the prosystemin transgene resulted in the constitutive expression of proteinase inhibitor proteins in the leaves of both the transformed root stock and the untransformed scion, demonstrating that expression of the prosystemin transgene generates a mobile wound signal. These results show that systemic signal propagation in the transgenic plants does not require wounding, and they support the proposed role of systemin as the mobile wound signal.

Agrobacterium tumefaciens↗
PubMed1994

Safety of fluconazole in the treatment of vaginal candidiasis. A prescription-event monitoring study, with special reference to the outcome of pregnancy.

A prescription-event monitoring (PEM) study has confirmed that fluconazole, a bis-triazole oral antifungal drug, is a safe and effective treatment for vaginal candidiasis. Useful information was available on 15,015 questionnaires returned by general practitioners. The events were compared with those recorded in PEM studies of itraconazole and 31 other drugs in a total of more than 330,000 patients. The frequency of events in the study of itraconazole was almost identical. Upper respiratory tract and genito-urinary infections were reported with above-average frequency but the relationship was with the disease being treated rather than the drug itself. No serious adverse effects were recorded with an unacceptably high incidence. None of the 125 deaths was caused by fluconazole. Although contraindicated for vaginal candidiasis in pregnancy, fluconazole was taken by 289 women at some time during the months before or during pregnancy; a follow-up study by questionnaire of the outcome of pregnancy showed fluconazole to be without harmful effect. It is concluded that fluconazole is a well tolerated drug in the treatment of vaginal candidiasis and is associated with very few adverse effects.

Adolescent↗
PubMed1994

Polypeptide signalling for plant defence genes.

The synthesis of proteinase inhibitor proteins in response to wounding is a defensive response against pest and pathogen attacks. Wounding of leaves results in the release of a mobile wound signal which induces proteinase inhibitor synthesis throughout the plant. The signal transduction pathway regulating this response is not fully understood, but several compounds have been identified which are capable of inducing proteinase inhibitor synthesis in tomato and potato leaves. These compounds include cell wall fragments of both plant and pathogen origin [1-3], abscisic acid [4], jasmonic acid [5] and, most recently, an 18-amino-acid polypeptide, called systemin, isolated from tomato leaves [6]. In this chapter, we describe the properties of systemin and its precursor prosystemin, and we summarize the evidence supporting a role for systemin as an initial signal that regulates proteinase inhibitor synthesis in response to wounding.

Amino Acid Sequence↗
PubMed1994

Bone mass during growth: the effects of exercise. Exercise and mineral accrual.

Intense exercise during childhood and adolescence may result in primary amenorrhea and low peak bone mineral density (BMD). After puberty, exercise may result in secondary amenorrhea and bone loss. Higher BMD in amenorrheic athletes than amenorrheic sedentary persons suggests that exercise may partly offsets the effects of amenorrhea. To examine this possibility, we measured BMD (g/cm2) by dual x-ray absorptiometry in 32 ballet dancer and 23 healthy controls of comparable age with regular menstrual cycles, 34 pre-pubertal female gymnasts bone age 8.9 +/- 0.2 years and 37 girls matched by bone age. Dancers had normal BMD at the weight bearing sites, not low, despite having oligomenorrhea, not high despite 32 hours of week dancing. BMD was lower by 4-6 percent at the non-weight bearing sites. BMD diminished in the dancers at the weight bearing femoral neck (r = -0.29, P = 0.1) and trochanter (r = -0.31, P = 0.09), and at the non-weight bearing arms (r = -0.29, P = 0.09) with increasing duration of amenorrhea. Dancers with less than 40 months amenorrhea had 5 to 7% higher BMD at the weight bearing, but not non-weight bearing sites. Dancers with more than 40 months amenorrhea had normal, not higher BMD at weight bearing sites and deficits of about 5 percent at non-weight bearing sites. In gymnasts, BMD was 10-15 percent (or 1 SD) higher than the bone age-predicted mean. Exercise may not offset the effects of amenorrhea. Bone loss may continue but from a higher level, perhaps attained prior puberty.

Adolescent↗
PubMed1993

Percutaneous transluminal coronary angioplasty of one major coronary artery when the contralateral vessel is occluded.

OBJECTIVES: In 193 patients we evaluated the safety and efficacy of angioplasty of a critical stenosis of the right coronary artery (52 patients) or the left anterior descending coronary artery (141 patients), with the contralateral coronary artery occluded and the circumflex artery being without significant stenosis. BACKGROUND: Attempted angioplasty of either the left anterior descending or the dominant right coronary artery when the contralateral vessel is occluded may trigger overwhelming left ventricular dysfunction or hemodynamic collapse, or both. METHODS: Immediate and late outcome (33 +/- 18 months) in the study group were compared with outcome in 214 patients who had angioplasty in both the left anterior descending and right coronary arteries and in 194 patients who had coronary artery surgery and were matched for number and location of significant lesions, ejection fraction, age, gender and study period. RESULTS: Left ventricular function was normal (38%) or mildly (34%), moderately (22%) or severely (6%) compromised. There were 11 (5.7%) emergency and 5 (2.6%) elective coronary artery operations, 3 (1.6%) myocardial infarctions and 1 in-hospital death in the study group. After discharge there were 25 (13.1%) elective coronary operations, 7 (3.7%) myocardial infarctions and 9 (4.7%) deaths in the study group. The incidence of death and myocardial infarction was similar in all groups, with 80% power to detect a 7% difference in adverse events. The study group had more elective surgery before and after discharge than did the surgical control group (p = 0.02). CONCLUSIONS: Dilating one major vessel when the contralateral vessel is occluded appears to be as safe as coronary surgery or two-vessel angioplasty. Incomplete revascularization in study group patients did not impair survival or increase myocardial infarction compared with the angioplasty and surgical control groups.

Actuarial Analysis↗
PubMed1993

Prescriber profile and post-marketing surveillance.

The response rate to requests to general practitioners (GPs) to supply post-marketing data on new drugs has been falling within the prescription-event monitoring (PEM) system organised by the Drug Safety Research Unit in Southampton, UK. To find out why, we looked at the characteristics of prescribers and the pattern of their prescribing for twenty seven PEM drugs and 543,788 treatments dispensed in England between September, 1984, and June, 1991. 28,402 GPs identified during PEM studies were divided into six groups according to the largest number of prescriptions for one or more of the drugs, ranging from group 1 (none of the drugs prescribed) to group 6 (one or more drugs for over 60 patients). From group 1 to group 6 the proportion of the GPs who were women decreased from 46% to 9%, and the proportion of overseas-qualified doctors increased from 13% to 47%. 10% of doctors who had prescribed most heavily accounted for 42% of total prescribing. 19 doctors had each prescribed a drug for more than 120 patients during the early post-marketing period. There was a consistent inverse relation between the number of prescriptions and the response to requests for post-marketing information. The overall response was 53% but the heaviest 10% of prescribers returned only 44% and the heaviest 1% returned only 34% of questionnaires. No differences in medical need can account for such variations in prescribing practice. Heavy prescribing by a minority of doctors during the period immediately following licensing for marketing may be placing patients at unnecessary risk. These doctors also affect the success of attempts to monitor the safety of new drugs.

Adverse Drug Reaction Reporting Systems↗
PubMed1993

Structure-activity of deleted and substituted systemin, an 18-amino acid polypeptide inducer of plant defensive genes.

The primary structure-activity relationships of systemin, an 18-amino acid polypeptide from tomato leaves that regulates the expression of two wound-inducible proteinase inhibitor genes in tomato and potato plants, were investigated. Analogs of systemin, the only example of a polypeptide signal from plants, were synthesized with progressive deletions of amino acids from both the NH2 terminus and COOH terminus and assayed in young excised tomato plants. All of the analogs exhibited severely decreased proteinase inhibitor-inducing activities, indicating that the entire 18-amino acid sequence is necessary for maximal activity. Deletion of the COOH-terminal Asp abolished inducing activity. Progressive replacement of each amino acid of the entire polypeptide with Ala revealed two regions, near residues Pro13, where Ala substitution reduced activity to less than 0.2%, and Thr17, which totally inactivated the analog. Other replacements with Ala had little or only moderate effects on activity. The two inactive analogs, des-Asp18 systemin and Ala17 systemin, were potent inhibitors of the inducing activity of the native systemin. These analogs, therefore, contain structural conformations sufficient for competition with systemin, but they are not competent for proteinase inhibitor gene induction. A synthetic COOH-terminal tetrapeptide, Met-Gln-Thr-Asp, retained low proteinase inhibitor inducing activity, but virtually any replacements with other amino acids either eliminated activity or reduced the activity to very low or nearly undetectable levels. These results indicate that residues near the COOH terminus of systemin are necessary for activity, possibly involving a phosphorylation at Thr17, and that other regions of the systemin sequence are important for interacting with a receptor(s) but are not sufficient to activate proteinase inhibitor gene expression.

Amino Acid Sequence↗