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Biomedical subjects

L Coleman

Publications and source records attributed to L Coleman.

At least 19 recordsLinked to original sources
PubMed2001

Differential kinetics of intracellular caspase-1-like and caspase-3-like enzyme activity in human alloreactive CD4(+) and CD8(+) T cells undergoing apoptosis.

The ICE-like families of serine proteases (caspases) have integral roles in apoptosis. These studies were performed to further understand the role of two critical caspases in relation to apoptotic regulation of the alloimmune response. A novel three-color cytofluorographic technique was utilized for measuring intracellular (in situ) caspase-1-like and caspase-3-like enzyme activity in responding CD4(+) and CD8(+) T cells over several time points of human mixed lymphocyte reactions (MLR). We found that activity levels of caspase 3 in both CD4(+) and CD8(+) responder cells began rising at day 10 of the MLR and peaked at day 14. By comparison, caspase 1 demonstrated the highest activity at day 7 in both cell subpopulations. These results coincided with the appearance of apoptotic cells among the alloreactive cells in the MLR. These findings demonstrate that intracellular caspase-1- and -3-like enzyme activity increases in both CD4(+) and CD8(+) alloreactive T cells as the primary response to allostimulatory cells progresses. While the kinetic profiles for these enzymes differed, both had a temporal association with the appearance of apoptosis in the MLR-generated cells. In all cases, the highest enzyme activity and presence of apoptosis was seen subsequent to the peak proliferative period. These results support the concept that changes in the rate and amount of apoptosis in alloreactive T cells is one mechanism by which the response to alloantigens is attenuated (i.e., tolerance) or sustained.

Apoptosis↗
PubMed2000

Platelet GP IIIa Pl(A) polymorphisms display different sensitivities to agonists.

BACKGROUND: Both inherited predisposition and platelet hyperreactivity have been associated with ischemic coronary events, but mechanisms that support genetic differences among platelets from different subjects are generally lacking. Associations between the platelet Pl(A2) polymorphism of GP IIIa and coronary syndromes raise the question as to whether this inherited variation may contribute to platelet hyperreactivity. METHODS AND RESULTS: In this study, we characterized functional parameters in platelets from healthy donors with the Pl(A) (HPA-1) polymorphism, a Leu (Pl(A1)) to Pro (Pl(A2)) substitution at position 33 of the GP IIIa subunit of the platelet GP IIb/IIIa receptor (integrin alpha(IIb)beta(3)). We studied 56 normal donors (20 Pl(A1,A1), 20 Pl(A1,A2), and 16 Pl(A2,A2)). Compared with Pl(A1,A1) platelets, Pl(A2)-positive platelets showed a gene dosage effect for significantly greater surface-expressed P-selectin, GP IIb/IIIa-bound fibrinogen, and activated GP IIb/IIIa in response to low-dose ADP. Surface expression of GP IIb/IIIa was similar in resting platelets of all 3 genotypes but was significantly greater on Pl(A2,A2) platelets after ADP stimulation (P=0.003 versus Pl(A1,A1); P=0.03 versus Pl(A1,A2)). Pl(A1,A2) platelets were more sensitive to inhibition of aggregation by pharmacologically relevant concentrations of aspirin and abciximab. CONCLUSIONS: Pl(A2)-positive platelets displayed a lower threshold for activation, and platelets heterozygous for Pl(A) alleles showed increased sensitivity to 2 antiplatelet drugs. These in vitro platelet studies may have relevance for in vivo thrombotic conditions.

Abciximab↗
PubMed1999

Heterotopic sternum transplant in rats: A new model of a vascularized bone marrow transplantation.

We introduced the heterotopic vascularized sternum transplant as a more simple and pure alternative to allogeneic hind limb transplantation for the study of bone marrow transplantation. We report the clinical and histopathological manifestations after transplantation of syngeneic and allogeneic sternal grafts with and without immunosuppression with FK-506. Syngeneic grafts maintained normal histology, whereas allografts showed rejection, which was prevented by FK-506. FK-506-treated allografts developed chimerism that was present throughout the observation period. Transplantation of the sternum may be a valuable model to study vascularized bone marrow transplantation and its effects on repopulation of bone marrow of the host, chimerism, and tolerance.

Animals↗
PubMed1999

Comparing contraceptive use surveys of young people in the United Kingdom.

Two sets of findings that emerged from a review of surveys assessing young people's use of contraception in the U.K. are outlined. First, the paper presents estimates of contraceptive use for this population subgroup and, second, it notes several limitations of surveys under review. The surveys use a wide range of indices in measuring these different aspects of contraceptive (including condom) use, which has made accurate cross-study comparisons difficult; hence most findings can only be presented as broad estimates (usually depicted within a percentage range), rather than as precise values. Nonuse of contraception among young people at last intercourse is 20 to 30% and nonuse of the condom lies between 40 and 50%. In light of this review process, the paper presents a critique of the indices used, labels the importance of using standardized and easily understood questions and measures, and highlights the most effective means of recording the potential for conception and/or sexually transmitted infection. Recommendations for those about to conduct further research in this area are added.

Adolescent↗
PubMed1999

Contrasting strategies used by young people to ensure condom use: some findings from a qualitative research project.

Interviews conducted among 56 young men and women (aged 16-19) reveal two contrasting strategies used to ensure condom use at first intercourse with a new partner. These are defined as verbal communication based strategies (involving some explicit discussion about contraception before intercourse) and non-verbal communication based strategies (where one partner takes responsibility for using condoms without discussing this with their partner). Whilst the former is argued as being the more effective strategy, this paper suggests an important role for the latter, particularly when young people find themselves in situations where initiating discussions about condom use is perceived as being particularly difficult.

Adolescent↗
PubMed1998

Attenders at young people's clinics in Southampton: variations in contraceptive use.

This paper presents findings from a survey of 424 people attending nine young people's clinics within the Southampton Community Health NHS Trust. In addition to recording some descriptive background data on the people attending the clinics, one major aim of the study was to investigate whether talking to the sexual partner about contraception before their first intercourse together and delaying this first intercourse influenced contraceptive use. Overall, 40 per cent of people attending the clinics were aged 16 or under, although there was some variation between clinics in the age groups attracted. Most clients were female (88 per cent), had ever had sexual intercourse (92 per cent), reported four or more lifetime partners (42 per cent) but only one partner within the last six months (73 per cent) and were currently in a relationship (75 per cent). Potential for contraception and sexually transmitted infection was widespread; 46 per cent (of non-virgins) had had intercourse without contraception at least 'a few times' and 18 per cent used condoms 'rarely' or 'never'. In terms of first intercourse with current/most recent partner, 17 per cent had not used any contraception and 32 per cent had failed to use condoms. The most important findings from this study were that use of contraception (and condoms in particular) on the occasion of first intercourse with the current or most recent partner was significantly associated with the following; if partners had talked to each other about contraception before having intercourse together for the first time (p<0.001), and also if this first intercourse was delayed beyond four weeks as opposed to over a few days of first 'going-out' together (p<0.001). Suggestions for further in-depth research are made.

Adolescent↗
PubMed1996

Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts.

Random high throughput sequencing of a human osteoclast cDNA library was employed to identify novel osteoclast-expressed genes. Of the 5475 ESTs obtained, approximately 4% encoded cathepsin K, a novel cysteine protease homologous to cathepsins S and L; ESTs for other cathepsins were rare. In addition, ESTs for cathepsin K were absent or at low frequency in cDNA libraries from numerous other tissues and cells. In situ hybridization in osteoclastoma and osteophyte confirmed that cathepsin K mRNA was highly expressed selecively in osteoclasts; cathepsins S, L, and B were not detectable. Cathepsin K was not detected by in situ hybridization in a panel of other tissues. Western blot of human osteoclastoma or fetal rat humerus demonstrated bands of 38 and 27 kDa, consistent with sizes predicted for pro- and mature cathepsin K. Immunolocalization in osteoclastoma and osteophyte showed intense punctate staining of cathepsin K exclusively in osteoclasts, with a polar distribution that was more intense at the bone surface. The abundant expression of cathepsin K selectively in osteoclasts strongly suggests that it plays a specialized role in bone resorption. Furthermore, the data suggest that random sequencing of ESTs from cDNA libraries is a valuable approach for identifying novel cell-selective genes.

Amino Acid Sequence↗
PubMed1996

Correlation of plasmids with infectivity of Borrelia burgdorferi sensu stricto type strain B31.

The correlation of plasmid profiles with infectivity was investigated by using five clones of Borrelia burgdorferi sensu stricto strain B31 (ATCC 35210). Plasmid profiles were determined by pulsed-field and two-dimensional gel electrophoresis. The 50% infectious dose (ID50) in hamsters was determined. The ID50 of the clone that possessed a full complement of eight linear and three circular plasmids was 10(3) cells. The loss of the 27.5- and 40-kb linear plasmids did not decrease the infectivity of these cells. Rather, the loss of the 27.5-kb linear plasmid was associated with a more disseminated infection. A moderate decrease of the ID50 from 10(3) to 10(5) cells correlated with the loss of the 9.0-kb circular plasmid and the 27.5-kb linear plasmid. A major loss of infectivity (ID50 > 10(3) cells) occurred with cells that lost the 24.7- and 27.5-kb linear plasmids and the 9.0-kb circular plasmid. A 3.0-kb HindIII fragment of the 24.7-kb linear plasmid was used as a probe to determine the presence of the homologous sequences in the three genospecies of Lyme disease spirochetes. An analysis of 21 infectious strains of B. burgdorferi sensu stricto, B. garinii, and B. afzelii revealed a consistent association of infectivity with strains possessing a linear plasmid (size range, 24 to 36 kb) that hybridized with the HindIII fragment. Western immunoblotting with hamster antisera against infectious B31 clone C-3 revealed two proteins with molecular masses of 28 and 43 kDa that were absent in the noninfectious B31 clone C-1. Additionally, a 14-kDa protein was absent in C-1 but present in infectious clone C-9 as shown by two-dimensional polyacrylamide gel electrophoresis.

Animals↗
PubMed1995

Cultivation of Borrelia burgdorferi from human tick bite sites: a guide to the risk of infection.

BACKGROUND: The risk of acquiring Lyme disease has been evaluated by xenodiagnostic procedures with laboratory strains of Borrelia burgdorferi and laboratory-reared Ixodes ticks, or by clinical trials in which diagnosis was based on clinical findings, culture, or serologic tests. OBJECTIVE: Our purpose was to determine the risk of infection from tick bites in a natural setting in which wild strains of B. burgdorferi were involved, by a biopsy culture technique. METHODS: Skin biopsy specimens were obtained from Ixodes scapularis tick bite sites, processed, and examined for the presence of B. burgdorferi. RESULTS: B. burgdorferi was cultivated from only 2 of 48 skin biopsy specimens. In both instances duration of tick attachment was approximately 24 hours. CONCLUSION: In a hyperendemic region for Lyme disease the risk of infection after a deer tick bite appears to be low, particularly if the tick has been attached for less than 24 hours.

Adult↗
PubMed1995

Assessment of capacity to comply with medication regimens in older patients.

OBJECTIVE: To develop an instrument that will facilitate and focus the assessment of a patient's capacity to adhere to a medication regimen before its initiation. DESIGN: This is a crossectional study that compares medical inpatients and outpatients to an age-matched, community-living, independent and relatively healthy group on their ability to adequately understand and implement hypothetical but realistic medication regimens. SETTING: Department of Veterans Affairs Medical Center, Sepulveda, California. PARTICIPANTS: Fifty-five older subjects (65 years or older) were divided into three groups: (1) generally healthy comparisons (standard group) (n = 20); (2) medical outpatients (n = 15); and (3) medical inpatients ready for discharge (n = 20). MEASUREMENTS: Older subjects were first tested on their capacity to comply with a difficult medication regimen presented in scenario form. If scores on the first scenario did not meet a standard group-derived cutoff point, further testing was conducted with a simpler scenario to identify greater levels of impairment. RESULTS: The outpatient group had significantly lower scenario scores than did the healthy comparison group (P < .03). The simpler scenario also showed a trend toward outpatient impairment (P = .06). In the comparison group, only 5% failed Scenario 1, and none failed Scenario 2. The outpatient group had the most difficulty, with 40% failing Scenario 1 and one-third of those failing Scenario 2. This differed significantly from the comparison groups (Fisher's Exact P < .03). In the inpatient group 20% failed Scenario 1 and 75% of those failing Scenario 2. The sensitivity and specificity of the Folstein Mini-Mental State Examination in identifying scenario-impaired subjects were 73% and 80%, respectively. Question types were analyzed to determine which questions were most frequently missed. Memory and judgment questions were found overall to be the most frequently missed. Healthy controls missed some judgment questions; however, the outpatient group was significantly worse in this category (chi 2 = 5.08; P = .01). All three groups improved their scenario performance significantly with question cueing. CONCLUSION: A significant number of medically ill outpatients encountered difficulty in understanding or remembering correctly hypothetical but realistic medication regimens. This suggests that an older medical patient's cognitive and functional capacity to comply with medication regimens of differing complexity can be specifically assessed before the start of the regimen and probably should be assessed in patients whose compliance capacity is in question. The assessment instrument under development in this study may be helpful in detecting those who need assistance with medications, thus identifying the need for intervention before poor compliance can lead to increased morbidity, rehospitalization, and increased medical costs.

Age Factors↗
PubMed1995

Pasteurella multocida septicemia and subsequent Pasteurella dagmatis septicemia in a diabetic patient.

Pasteurella species may cause zoonotic infections of humans. Serious systemic infections with these organisms are unusual, but they may occur in individuals with predisposing underlying illnesses. Occurrences of bacteremia due to P. multocida are infrequent, and P. dagmatis bacteremia is even rarer. We report independent occurrences of P. multocida and P. dagmatis septicemia in the same diabetic patient after contact with two pet dogs. We review the history of Pasteurella species and discuss the biochemical and clinical features of its association with zoonosis.

Animals↗
PubMed1994

Indications for and the significance of seminal vesicle irradiation during 3D conformal radiotherapy for localized prostate cancer.

PURPOSE: To evaluate the use of pretreatment prostate specific antigen, Gleason score, and clinical stage as predictors of the risk of seminal vesicle involvement in patients with clinically localized prostatic cancer, and to determine the impact of excluding the seminal vesicles on the dose received by surrounding normal tissues. METHODS AND MATERIALS: An empirically derived equation combining the preoperative prostate specific antigen and Gleason score was applied to 188 patients treated with radical prostatectomy, for whom pathologic evaluation of the seminal vesicles was available. High and low risk groups for seminal vesicle involvement were defined using this equation. The observed risks of seminal vesicle involvement was compared to the predicted risk using the preoperative prostate specific antigen, Gleason score or clinical stage alone or using the empirical equation. Dose-volume histograms for five patients treated using six-field conformal radiotherapy were compared including and excluding the seminal vesicles. RESULTS: Using the empirically derived equation, a low risk group of 109 patients was identified with a calculated risk of seminal vesicle involvement of < or = 13% and an observed incidence of 7.3%. Among the high risk group of 79 patients, which included all patients with a calculated risk > 13%, 37% had seminal vesicle involvement (p < 0.001 low vs. high risk). Twenty percent of the rectal volume received on average above 86% of the total dose for the five plans which included the seminal vesicles compared to 68% for the five plans excluding the seminal vesicles. The doses to 40% of the rectal volume were 64% and 37% if the seminal vesicles were included and excluded, respectively. The dose to the bladder and femoral heads was also decreased but to a lesser extent. CONCLUSION: The empirical formula predicts risk of seminal vesicle involvement with a higher degree of significance for a larger number of patients than either Gleason score, clinical stage, or prostate specific antigen alone. Based on an analysis of our first 100 patients treated with definitive conformal therapy alone, approximately 47% of those patients could have been treated excluding the seminal vesicles. Excluding the seminal vesicles may allow us to go to a higher total dose with less rectal toxicity.

Humans↗
PubMed1994

Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and Gleason score in men with clinically localized prostate cancer.

PURPOSE: To evaluate the predictive value of an empirically derived equation for identifying patients with clinically localized prostate cancer at low and high risk for harboring occult lymph node metastasis. METHODS AND MATERIALS: A simple equation for estimating the risk of positive lymph nodes was empirically derived from a nomogram published by Partin et al. demonstrating the value of combining the pre-treatment prostate specific antigen and Gleason Score in predicting the risk of lymph node metastasis for patients with clinically localized prostate cancer. The risk of positive nodes (N+) was calculated using the equation; N+ = 2/3(PSA) + (GS-6) x 10, where PSA and GS are the pre-treatment prostate specific antigen and Gleason Score respectively, and the calculated risk is constrained between 0-65% for a PSA < or = 40 ng/ml (as in the nomogram). To test the general applicability of this equation, we reviewed the pathologic features of 282 of our patients who had undergone a radical prostatectomy. RESULTS: Based on 212 patients for whom the pre-operative prostate specific antigen's and Gleason Scores were available, we identified 145 patients with a calculated risk of positive nodes of < 15%, (low risk group) and 67 patients with a calculated risk as > or = 15% (high risk group). The observed incidence of positive nodes was 6% and 40% among the low and high risk groups respectively (p < 0.001). When used alone neither clinical stage, pre-treatment prostate specific antigen nor the pre-treatment Gleason Score was as useful in identifying the largest low and high risk groups. CONCLUSION: Using the equation described we confirmed the general applicability of the nomogram reported by Partin et al. and identified patients at low and high risk for lymph node involvement. Based on these data we have adopted a policy of omitting whole pelvic irradiation in patients identified as low risk.

Biomarkers, Tumor↗
PubMed1994

Cultivation of Borrelia burgdorferi from the blood of two patients with erythema migrans lesions lacking extracutaneous signs and symptoms of Lyme disease.

BACKGROUND: We recently demonstrated that cultivation of Borrelia burgdorferi from skin biopsy specimens obtained from erythema migrans lesions was an efficacious procedure to confirm the diagnosis of Lyme disease. OBJECTIVE: Our purpose was to investigate the efficacy of our microbiologic technique on blood samples obtained from patients with Lyme disease and erythema migrans. METHODS: Whole blood samples were obtained from 52 patients with erythema migrans and early localized or early disseminated Lyme disease and placed into polystyrene tubes containing 6 ml of modified Barbour-Stoenner-Kelly medium, processed, and examined for B. burgdorferi by dark-field microscopy. RESULTS: B. burgdorferi was cultured from the blood of two of our 52 patients (4%). Clinically, both of these patients were considered to have early localized Lyme disease. CONCLUSION: The culture of B. burgdorferi from the blood of patients with early Lyme disease does not appear to be an efficacious procedure to confirm the diagnosis of Lyme disease. However, the demonstration of spirochetemia in patients with erythema migrans without any extracutaneous evidence of disseminated illness does have therapeutic significance.

Adult↗
PubMed1993

Childhood sexual experiences with adults. A comparison of reports by women psychiatric patients and general-practice attenders.

Reports of childhood sexual experiences with adults were collected from 120 women attending general-practice surgeries and 115 women psychiatric patients. The method of study, research team and county of residence were the same for the two groups. The psychiatric patients tended to report rates of events higher than the general-practice attenders by a factor of 2-3. The results suggest an association between such experiences and later psychiatric patienthood and are compatible with a causal role for them in some cases.

Adolescent↗
PubMed1992

Failure of Borrelia burgdorferi to survive in the skin of patients with antibiotic-treated Lyme disease.

BACKGROUND: Borrelia burgdorferi has been cultivated from clinically normal skin (previous erythema migrans sites) after antibiotic therapy for Lyme disease. OBJECTIVE: We investigated the possibility of similar findings in 13 of our patients with antibiotic-treated Lyme disease from whom B. burgdorferi was cultivated from their erythema migrans lesions before antibiotic therapy. METHODS: After treatment with doxycycline or a combination of amoxicillin and probenecid, skin biopsy specimens were obtained from clinically normal skin adjacent to the previous biopsy sites and cultured. RESULTS: B. burgdorferi was not cultivated from these posttreatment biopsy sites. CONCLUSION: The failure of B. burgdorferi to survive in the former erythema migrans sites of our antibiotic-treated patients, as well as their favorable clinical response, supports the use of doxycycline or combined amoxicillin and probenecid in the treatment of early Lyme disease but does not preclude the survival of the organism in other tissues.

Adult↗