Measurement of activities of cyclobutane-pyrimidine-dimer and (6-4)-photoproduct photolyases.
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Chromatography, Thin Layer↗
Biomedical subjects
P Hoffman
Publications and source records attributed to P Hoffman.
Mechanical valve replacement in congenital heart disease in children.
BACKGROUND AND AIM OF THE STUDY: The study aim was to analyze predictive factors of long-term results after mechanical heart valve replacement in children. METHODS: Forty-four patients (19 males, 25 females; mean age 8.9+/-3.9 years, median 7.0 years, range: 1.3 to 15 years) underwent heart valve replacement with mechanical prostheses. Of these patients, 25 had left atrioventricular valve replacement (LavVR) (18 mitral, six tricuspid in corrected transposition of the great arteries (TGA), one common in a univentricular heart), 13 had aortic valve replacement (AVR) and six had tricuspid valve replacement (TVR). The etiology of the valvular disease was congenital in all patients, and complicated by infective endocarditis in seven (16%). Fifteen patients had undergone previous procedures and 16 required simultaneous repair of associated lesions. The mean size of the implanted prosthesis was 26 mm (range: 19-29 mm) for LavVR, 29.7 mm (range: 23-33 mm) for TVR, and 21.9 mm (range: 19-25 mm) for AVR. Postoperatively, all patients received oral anticoagulation. The mean follow up was 6.8+/-3.5 years (total 290 patient-years). RESULTS: There was no early mortality, but three patients (7%) died later; all late deaths occurred in patients with LavVR. There were two sudden deaths, both in patients with complex congenital heart disease and heart failure (before the ACE inhibitor era), and one valve-related death from thrombotic occlusion of a mitral prosthesis. Five patients were reoperated on; three for patient-prosthesis mismatch, one for periprosthetic leak, and one for aortic dissection due to Marfan's syndrome. Thrombotic obstruction occurred in three patients; two in the tricuspid position were treated successfully with thrombolysis, but one in the left atrioventricular position proved fatal. After seven years, the survival rate was 93.4%. CONCLUSIONS: Mechanical heart valve replacement in children aged over one year with congenital heart disease can be performed with satisfactory early and late results. Mechanical valves of >23 mm diameter in the atrioventricular position in the systemic ventricle, and >21 mm in the aortic orifice, can offer excellent long-lasting hemodynamic performance. However, mechanical valves in the tricuspid position are prone to develop thrombotic occlusion.
Adolescent↗
[Benign testicular tumors in children. Value of simple tumorectomy].
From 1984 to 1999, the authors observed 18 intratesticular tumours, 13 of which corresponded to benign lesions. The objective of this study is to define preoperative and intraoperative criteria of benign lesions in order to allow conservative management (simple excision or enucleation) and to analyse the results of this treatment. The 13 boys of this series were between the ages of 5 months and 14 years (mean: 7.1 years). The lesion presented as scrotal swelling in 12 cases and gynaecomastia in 1 case. Tumour markers (alphafoetoprotein, beta HCG) were at the limit of normal for age. Ultrasonography was performed in every case. In each case, treatment consisted of primary exposure of the pediclc with clamping then exteriorization and macroscopic examination of the lesion. Frozen section examination was performed in 11 cases. Treatment consisted of 9 enucleations and 4 orchidectomies. The final histology concluded on epidermoid cyst or simplified teratoma with exclusively ectodermal development in 4 cases, multi-differentiated teratoma in 2 cases, sex cord tumour in 2 cases, simple cyst in 2 cases, rete testis dysplasia in 1 case, cavernous haemangioma in 1 case, and vestigial cyst in 1 case. There was no discordance between the final histological examination and the frozen section examination. The mean follow-up is 4.4 years. No secondary atrophy and no local or distant recurrence was observed in the 9 cases of enucleation. In conclusion, testicular tumours are often benign in children. Selection based on a body of clinical, laboratory, radiological and frozen section histological evidence should allow carcinologically safe conservative surgery with an aesthetic, psychological and functional benefit for the child.
Adolescent↗
Long-term follow-up results of balloon valvuloplasty for congenital aortic stenosis: predictors of late outcome.
AIMS: Long-term follow-up of patients with aortic valve stenosis undergoing balloon valvuloplasty was evaluated with respect to survival, the need for repeat intervention and factors predicting late outcome. METHODS AND RESULTS: Forty-five patients between 3.5 to 23 years old (mean 11.7 +/- 4.5) were followed for 62 +/- 30 months (range 11-122). The transvalvar aortic gradient decreased from 84 +/- 20 to 36 +/- 10 mmHg (p < 0.001) and remained significantly lower (50 +/- 26 mmHg; p < 0.001) at follow-up. At that time, 10 patients (including 4 with significant valve incompetence) had gradients >/= 60 mmHg. The procedure resulted in significant valve incompetence (grade >/= 3) in 8 patients (17.8%). There was a progression of incompetence and 13 patients (28.9%) had significant regurgitation at follow-up. All survived. Fifteen patients (33.3%) required re-intervention 51 +/- 24 months after valvuloplasty. The indications were: aortic stenosis in 5 patients; regurgitation in 6 patients; and stenosis with regurgitation in 4 patients. Actuarial freedom from re-intervention at 2, 4, 6 and 8 years was 96%, 88%, 61% and 56% of patients, respectively. The residual post-valvuloplasty gradient was the only predictor of re-intervention for valve stenosis (odds ratio = 3.2 for every 10 mmHg gradient increase; p = 0.017). A residual post-valvuloplasty gradient >/= 40 mmHg increased the relative risk of re-intervention sixfold. The immediate post-valvuloplasty aortic regurgitation grade was the only risk factor of re-intervention for regurgitation (odds ratio = 34 for every incompetence degree increase; p = 0.0019). Incompetence grade >/= 2 increased the risk of re-intervention tenfold. CONCLUSIONS: Valvuloplasty carries the risk of development of valve incompetence, which progresses with time. Some patients develop restenosis. The </= 10 year survival after the procedure is excellent, and 56% of patients are free of re-intervention at 8 years. The immediate post-valvuloplasty incompetence grade and transvalvar gradient are the predictors of late re-intervention.
Adolescent↗
[Pulmonary hypertension in adult patients with secundum atrial septal defect before surgery and in long-term follow-up].
The aim of the study was to determine pre- and postoperative systolic pulmonary pressure in adult patients with ASD II. The study group consisted of 224 pts who had undergone surgical repair of ASD II in between 1987-1993. The mean postoperative follow-up was 7.5 y. The group (160 F, 66 M aged 17-66 years) was divided on 3 subgroups: age under 20 y--27 pts; 20-40 y--131 pts; and older then 40 y--66 pts. We analysed pre- and postoperative parameters: pulmonary hypertension (PASP-Doppler) and functional class (NYHA). Preoperative pulmonary pressure was 35-50 mm Hg in 69 pts (30.8%) of the group, and over 50 mm Hg in 29 (12.9%). In long-term follow-up of 98 (43.8%) operated patients with coexisting pulmonary hypertension, significant reduction of pulmonary pressure was observed in all patients, even in patients over 40 y. Functional class of heart failure NYXHA improved as well in all patients.
Adolescent↗
MUC1 synthetic peptide inhibition of intercellular adhesion molecule-1 and MUC1 binding requires six tandem repeats.
We reported recently that breast cancer-associated MUC1 is a ligand for intercellular adhesion molecule-1 (ICAM-1; L. H. Regimbald et al., Cancer Res., 56: 4244-4249, 1996). We report here the results of a competitive indirect binding assay to detect the molecular requirements for binding between ICAM-1 and MUC1. The assay involved inhibition of the binding of recombinant human ICAM-1 to a murine breast adenocarcinoma cell line transfected with human MUC1. The addition of a library of human MUC1 synthetic peptides ranging from 9 to 24 amino acids (aa) showed minimal or no inhibition. However, a 120-aa peptide that corresponds to six tandem repeats of the human mucin MUC1 was as effective an inhibitor as purified tumor MUC1 and MUC1 epitope (PDTRPAP)-specific antibody (B27.29). We conclude that the number of MUC1 tandem repeats necessary for an ordered tertiary structure (D. Fontenot et al., Cancer Res., 53: 5386-5394, 1993) is also important for ICAM-1 recognition. These findings are similar to those described recently for MUC1 induction of T-cell anergy (B. Agrawal et al., Nat. Med., 4: 43-49, 1998). This suggests that the anergy induction by MUC1 may be due to ICAM-1 binding by MUC1.
Adenocarcinoma↗
Chorioamnionitis and pregnancy outcome in HIV-infected African women. Pregnancy and HIV Study Group.
OBJECTIVE: To assess the role of chorioamnionitis (CAM) on pregnancy outcome in HIV-1-infected (HIV-positive) pregnant women, treated for sexually transmitted diseases (STDs), during the last trimester of pregnancy in Kigali, Rwanda. METHODS: At inclusion in a prospective cohort, from July 1992 to August 1993, 561 pregnant women between 24 and 28 weeks were systematically screened for HIV infection, STDs, anemia, malaria, and hepatitis B infection; a CD4 lymphocyte count was performed. Until delivery, each woman enrolled had a monthly clinical follow-up with STD treatment when needed. The pregnancy outcome was recorded. Diagnosis of CAM was based on histologic examination of the placenta. RESULTS: Among the 275 placentas of HIV-negative women and 286 placentas of HIV-positive women examined, CAM was diagnosed (CAM-positive) in 27 HIV-positive women (9.8%) and in 28 HIV-negative women (9.8%). No statistical association was found between CAM and the following variables, independent of the HIV serostatus: age, parity, hepatitis B, anemia, STDs, and immune deficiency. Among HIV-negative women, CAM was significantly associated with prematurity (relative risk [RR] = 3.0; 95% confidence interval [CI] = 1.5-6.3), stillbirth (RR = 4.2; 95% CI = 1.6-11.0) and premature rupture of membranes (RR = 2.9; 95% CI = 1.4-6.1). Among HIV-positive women, early neonatal mortality was the only adverse outcome associated with CAM (RR = 2.0; 95% CI = 1.6-11.0). CONCLUSIONS: In our study, the prevalence of CAM was low and no risk factor of CAM was identified, a probable consequence of the control factor of STDs. CAM was strongly associated with adverse pregnancy outcomes in HIV-infected women, reflecting a possible deleterious effect of HIV.
Chorioamnionitis↗
Ischemic neurologic event in a child as a result of ventricular septal aneurysm.
Aneurysm of the interventricular septum without a shunt was found by means of transthoracic echocardiography in a 6-year-old boy with acute hemiparesis. Until the time of the incident, he had been healthy. The aneurysmal sac contained 2 clots, presumably resulting in the ischemic cerebral infarct. On the basis of the echocardiographic scan, successful surgery was performed. To the best of our knowledge, this is the first report describing such dramatic sequelae of interventricular septal aneurysm.
Brain Ischemia↗
Chemical structure of bismuth compounds determines their gastric ulcer healing efficacy and anti-Helicobacter pylori activity.
The recognition of the role of Helicobacter pylori in the pathogenesis of peptic ulcer disease has led to renewed interest in bismuth pharmacology since bismuth compounds have both anti-Helicobacter pylori and ulcer healing properties. The precise chemical structure of current bismuth compounds is not known. This has hindered the development of new and potentially more efficacious formulations. We have created two new compounds, 2-chloro-1,3-dithia-2-bismolane (CDTB) and 1,2-[bis(1,3-dithia-2-bismolane)thio]ethane (BTBT), with known structure. In a rat model of gastric ulceration, BTBT was comparable to, and CDTB was significantly less effective than colloidal bismuth subcitrate in healing cryoprobe-induced ulcers. However, both BTBT and CDTB inhibited H. pylori growth in vitro at concentrations <1/10 that of colloidal bismuth subcitrate. The effects on ulcer healing are not mediated by suppression of acid secretion, pepsin inhibition, or prostaglandin production. Since all treated animals received the same amount of elemental bismuth, it appears that the efficacy of bismuth compounds varies with compound structure and is not simply dependent on the delivery of bismuth ion. Because the structure of the novel compounds is known, our understanding of the relationship of bismuth compound structure and to biologic activity will increase. In the future it may be possible to design other novel bismuth compounds with more potent anti-H. pylori and ulcer healing effects.
Animals↗
Acute effects of ethanol on pharmacologically isolated kainate receptors in cerebellar granule neurons: comparison with NMDA and AMPA receptors.
Comparisons of acute ethanol's effects on individual members of the three major families of ionotropic glutamate receptors (kainate, AMPA, and NMDA) have been performed only with recombinant receptors. However, no study has compared the acute effects of ethanol on individual members of each one of these receptor families in the same neuron. We accomplished this task by using cultured cerebellar granule neurons and LY303070 (GYKI-53784), a noncompetitive and selective AMPA receptor antagonist. Ethanol concentrations of 25, 50, 75, and 100 mM decreased the amplitude of pharmacologically isolated kainate-activated currents by 3 +/- 1, 9 +/- 2, 14 +/- 2, and 22 +/- 3% (n = 8), respectively. The magnitude of the ethanol-induced inhibition of nonselective kainate-activated currents, i.e., in the absence of LY303070, and currents activated by submaximal AMPA concentrations was not significantly different from that obtained with isolated kainate currents. However, the magnitude of the ethanol-induced inhibition of NMDA receptor-activated currents was about twofold greater than that of kainate and/or AMPA receptors.
Animals↗
Characterization of an acidic-pH-inducible stress protein (hsp70), a putative sulfatide binding adhesin, from Helicobacter pylori.
The in vitro glycolipid binding specificity of the gastric pathogen Helicobacter pylori is altered to include sulfated glycolipids (sulfatides) following brief exposure of the organism to acid pH typical of the stomach. This change is prevented by anti-hsp70 antibodies, suggesting that hsp70 may be a stress-induced surface adhesin, mediating sulfatide recognition. To facilitate investigation of the role of hsp70 in attachment, we have cloned and sequenced the H. pylori hsp70 gene (dnaK). The hsp70 gene was identified by probing a cosmid DNA library made from H. pylori 439 with a PCR amplicon generated with oligonucleotides synthesized to highly conserved regions of dnaK. The 1.9-kb H. pylori hsp70 gene encodes a product of 616 amino acids. Primer extension analysis revealed a single transcription start site, while Northern blot analysis established that hsp70 was preferentially induced by low pH rather than by heat shock. The ability of H. pylori to alter its glycolipid binding specificity following exposure to low pH by upregulating hsp70 and by expressing hsp70 on the bacterial surface may provide a survival advantage during periods of high acid stress.
Acids↗
The leukointegrin alpha d/beta 2 (alpha d/CD18): specific changes in surface expression in patients on hemodialysis.
Alpha d/CD18 is a newly discovered leukocyte adhesion molecule with sequence homology to CD11a, b and c of the beta 2 integrin family. Little is known about alpha d expression in vivo, particularly how it compares with the other beta 2 integrins. Previous studies have demonstrated that beta 2 integrin expression, particularly CD11b, is upregulated in vivo during hemodialysis (HD) with complement activating membranes. These changes may contribute to the immunologic abnormalities seen in HD patients. Given the well described changes of beta 2 integrins in these patients, we hypothesized that alpha d expression could also be altered by HD. Using flow cytometry with two specific antibodies to alpha d, alpha d expression in healthy adults (n = 16) was compared on macrophages (MO) > polymorphonuclear cells (PMNs) > lymphocytes (LY). Phorbol ester treatment of leukocytes in vitro significantly increased expression on MO and PMN, but not LY. Chronic HD patients at baseline (n = 15) had elevated (P < 0.05) alpha d mean channel fluorescence (MCF) on MOs, PMNs and LYs compared to normals. PMN alpha d MCF increased at 15 min into HD, but then returned to baseline levels at 180 min. Alpha d MCF for LYs decreased at 180 min, while MOs levels were unchanged. Alpha d expression is increased in chronic renal failure and further regulated by hemodialysis, but with unique characteristics compared to the other beta 2 integrins. Alpha d may be important in abnormal cell-cell contacts in renal failure.
Adult↗
An Arabidopsis photolyase mutant is hypersensitive to ultraviolet-B radiation.
Photolyases are DNA repair enzymes that use energy from blue light to repair pyrimidine dimers. We report the isolation of an Arabidopsis thaliana mutant (uvr2-1) that is defective in photorepair of cyclobutylpyrimidine dimers (CPDs). Whereas uvr2-1 is indistinguishable from wild type in the absence of UV light, low UV-B levels inhibit growth and cause leaf necrosis. uvr2-1 is more sensitive to UV-B than wild type when placed under white light after UV-B treatment. In contrast, recovery in darkness or in light lacking photoreactivating blue light results in equal injury in uvr2-1 and wild type. The uvr2-1 mutant is unable to remove CPDs in vivo, and plant extracts lack detectable photolyase activity. This recessive mutation segregates as a single gene located near the top of chromosome 1, and is a structural gene mutation in the type II CPD photolyase PHR1. This mutant provides evidence that CPD photolyase is required for plant survival in the presence of UV-B light.
Apoenzymes↗
Prospering under PPS. A guide for financial managers.
The survivors of PPS will be those organizations that gain knowledge and control of their true costs, learning how to manage them within the constraints imposed by the new payment system. It is difficult to predict the exact details of PPS legislation; however, several principles of PPS appear to be emerging that will probably be a part of the finished legislative product. Together they provide a framework sufficient to begin the process of analyzing how to prepare for PPS.
Cost Control↗
Clinical exemplar: his name was Beauty.
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Humans↗
Synovial distribution of alpha d/CD18, a novel leukointegrin. Comparison with other integrins and their ligands.
OBJECTIVE: To define the synovial distribution of the novel leukointegrin alpha d/CD18, and compare this with other members of the beta 2-integrin family of adhesion molecules, and their counter-receptors. METHODS: Monoclonal antibodies to the CD3, CD14, CD29, CD68, beta 2-integrin, and immunoglobulin supergene families were used to immunohistologically define the distribution of these molecules in synovial tissue samples from normal subjects and osteoarthritis (OA) and rheumatoid arthritis (RA) patients. RESULTS: The normal synovial lining cell layer (SLC) expresses CD68, vascular cell adhesion molecule 1, beta 1-integrin (CD29), the beta 2-integrins CD11b/CD18 (alpha m/beta 2, Mac-1), and alpha d/CD18, whereas CD11a/CD18 (alpha L/beta 2, lymphocyte function-associated antigen 1) and CD11c/CD18 (alpha x/beta 2, gp150/95) expression is generally absent. In RA synovitis, expression of beta 2-integrins in the SLC increases in proportion to the degree of hyperplasia. The ratio of cells in the SLC which express CD11c/CD18 increases substantially, approaching that of CD11b/CD18 and alpha d/CD18, while there is minimal increase in CD11a/CD18 expression. In the sublining areas of the tissues, aggregates and diffuse infiltrates of CD3/CD11a/ICAM-3+ lymphocytes are interspersed among CD68/CD14/CD11b/alpha d+ macrophages. A number of aggregates demonstrate intense alpha d staining of the lymphocytes. The synovial endothelium variably expresses intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and vascular cell adhesion molecule 1 (VCAM-1), with minimal evidence of ICAM-3 expression. CONCLUSION: The leukointegrin alpha d/CD18 is expressed constitutively by synovial macrophages and macrophage-like lining cells. In rheumatoid synovitis, the intense coexpression of this integrin and its known counter-receptor, ICAM-3, in the inflammatory infiltrates, suggests a potential role for this adhesion pathway in cellular interactions occurring the synovium.
Adult↗
Acidic pH changes receptor binding specificity of Helicobacter pylori: a binary adhesion model in which surface heat shock (stress) proteins mediate sulfatide recognition in gastric colonization.
The gastric pathogen helicobacter pylori is one of a number of bacteria which bind specifically to gangliotetraosylceramide, gangliotriaosylceramide, and phosphatidylethanolamine in vitro at neutral pH. Since this organism encounters an acid pH during initial infection of the stomach, we have monitored the effect of pH on receptor binding specificity and found induction of specific binding to sulfoglycolipids (sulfatide) following brief treatment at low pH. We have previously shown that heat shock proteins (hsps) bind to sulfatide, and the suspicion that this was a stress-induced response is supported by the fact that a similar change in H. pylori binding specificity was observed if the organisms were briefly exposed to heat shock treatment. Following the stress stimulus, the change in glycolipid binding specificity was prevented by the inclusion of inhibitors of protein synthesis or by incubation with anti-hsp antibodies. Expression of hsps in the surface extract and surface reactivity with anti-hsp antibodies correlated with the change in glycolipid binding specificity. Despite the presence of high levels of H. pylori cell surface urease activity which may neutralize the microenvironmental pH, the acid-induced change in binding specificity was enhanced in the presence of urea. These studies suggest that cell surface hsps mediate sulfatide recognition by this organism under stress conditions. A binary receptor model is proposed for gastric colonization by H. pylori.
Adhesins, Bacterial↗
[Complete regression of cardiac non-Hodgkin's lymphoma after 23 months with chemotherapy].
The authors report the case of a non-Hodgkin malignant lymphoma (NHL) of the heart presenting with syncope. The diagnosis of a cardiac tumours was made by echocardiography. Myocardial biopsy enabled diagnosis of a highly malignant NHL in a patient with a history of low grade NHL. Chemotherapy with CNOP (Cyclophosphamide, Novantrone, Oncovin, Prednisone) induced total regression of the tumour. The patient is in total remission 23 months later. The authors emphasise the value of echocardiography in the diagnosis and follow-up of this pathology. The case is also noteworthy because of the unusual transformation of a low grade to a high grade cardiac NHL.
Antineoplastic Combined Chemotherapy Protocols↗