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Biomedical subjects

M Lieber

Publications and source records attributed to M Lieber.

At least 19 recordsLinked to original sources
PubMed2006

Human endothelial cell septins: SEPT11 is an interaction partner of SEPT5.

The septin SEPT11 is a novel member of the highly conserved septin family. Septins are cytoskeletal GTPases, which form heteropolymeric complexes. They are involved in cytokinesis and other cellular processes, such as vesicle trafficking and exocytosis. SEPT11 has strong homology to SEPT8. Previously, we identified the interaction of SEPT5 and SEPT8. Using the yeast two-hybrid system, we now demonstrate that SEPT11 partners with SEPT5. The molecular interaction of SEPT11 with SEPT5 was verified by coprecipitation of SEPT5 and SEPT11 from lysates of the human T-cell leukaemia cell line JURKAT and by fluorescence resonance energy transfer. The interaction between SEPT5 and SEPT11 requires the GTP-binding domain and the C-terminal extension. Western analysis in various mouse and human tissues revealed that expression of SEPT11 is restricted to the same tissues as those expressing SEPT5, suggesting that SEPT11 and SEPT5 are components of a cell-specific septin complex. SEPT5, which is expressed in human umbilical vein endothelial cells (HUVECs), has been reported to play an important role in exocytosis. We now report that HUVECs also express SEPT11. Given the interactivity between SEPT5 and SEPT11 as shown above and their coexpression in HUVECs, it may be that a complex formed by these two proteins is involved in the exocytosis mechanism in HUVECs.

Animals↗
PubMed2006

Hyperbaric oxygen in treatment of neonatal arterial thromboembolism of lower extremities.

Arterial thromboembolism (TE) in the absence of current or recent history of a central catheter is a rare condition in newborn period. We report a case of severe lower extremities arterial TE of unclear etiology in a full-term neonate. By adding hyperbaric oxygenation to thrombolytic and antithrombotic therapy, we achieved improved perfusion of the upper leg tissues, preserving the knee and enabling below-the-knee amputation.

Amputation, Surgical↗
PubMed2004

Temporal lobe volumes in patients with hippocampal sclerosis with or without cortical dysplasia.

BACKGROUND: Recent MRI-based volume reconstruction studies in intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) suggested atrophy that extends to the adjacent neocortical areas. OBJECTIVE: To study the extent of temporal lobe volume (TLV) abnormalities in patients with pathologically confirmed HS (with or without cortical dysplasia [CD]) who underwent anterior temporal lobectomy for the treatment of drug-resistant TLE. METHODS: Fifty patients (right TLE: n = 24; left TLE: n = 26) were found to have HS (hippocampal cell loss of >30%). Associated neocortical CD was seen in 20 patients (43%). MRI-based TLVs and hippocampal and hemispheric volume reconstructions in all patients were compared between pathologic groups and with volumes acquired from 10 age-matched control subjects. RESULTS: TLVs ipsilateral to the epileptogenic zone in patients with TLE were smaller than TLVs in control subjects (p < 0.01). In patients with left TLE, TLVs ipsilateral to the epileptogenic zone were smaller than contralateral TLVs (left: 66.6 +/- 8.3 cm3, right: 74.9 +/- 10.0 cm3; p < 0.001). In patients with right TLE, there were no significant asymmetries. The contralateral TLVs (regardless of the side of surgery) were smaller in the HS + CD group than the HS group (HS + CD group: 74.9 +/- 8.6 cm3, HS group: 79.7 +/- 6.6 cm3; p < 0.05). Patients with HS + CD had a tendency to have less hippocampal atrophy and slightly smaller TLVs ipsilateral to the epileptogenic zone, accounting for significantly smaller TLV/hippocampal volume ratios compared with patients with HS alone. CONCLUSIONS: Drug-resistant TLE due to HS is associated with extrahippocampal temporal lobe atrophy. The presence of bilateral temporal lobe atrophy is suggestive of a more widespread (bilateral) temporal lobe involvement in patients with HS and CD.

Adolescent↗
PubMed2004

Are men treated better than women? Outcome of male versus female patients after CABG using bilateral internal thoracic arteries.

BACKGROUND: Apart from smaller native coronary arteries a lower number of anastomoses and a lower ITA incidence have been suggested as being responsible for the increased mortality in female patients compared to males. The aim of this study was to clarify whether the outcome of females might be a consequence of a different regimen in anastomosis and ITA frequency. METHODS: We evaluated operative data and early outcome of 6906 patients with isolated CABG operated between 1/96 - 7/03 3064 out of 5381 males received bilateral ITA (BITA) vs. 750 of 1525 females. Single ITA (SITA) was performed in 2126 males and 704 females. RESULTS: Demographic and operative data: average age for male patients was 64.0 +/- 9.2 years, for females 68.5 +/- 8.6 years ( p < 0.05). The prevalence of diabetes mellitus was significantly higher in females (34.6 % vs. 27.4 %, p < 0.01). Body mass index (BMI, 26.6 vs. 27.4 mean), incidence of main stem stenosis (23.0 % vs. 23.5 %), ejection fraction < 40 % (7.8 % vs. 10.1 %), urgent or emergent operations (13.1 % vs. 11.3 %) and number of performed anastomoses (3.2 vs. 3.5 mean) showed no significant difference between males and females. Total ITA frequency did not differ (95.3 % vs. 96.5 %), but BITA frequency was significantly higher (56.9 % vs. 49.2 %, p < 0.01) in male patients. Overall 30-day mortality was 2.8 % for males vs. 4.1 % ( p < 0.05) for females. Cardiac-related mortality was significantly higher in female patients (2.6 % vs. 1.1 %, p < 0.01). Non-cardiac-related mortality did not differ significantly. Graft-related mortality for males and females revealed 2.7 % in the BITA, 3.3 % in the SITA group and 6.9 % for patients without ITAs and reached statistical significance ( p < 0.01) for SITA or BITA vs. the no-ITA group, but not for BITA vs. SITA grafting. Nevertheless cardiac-related mortality in male and female patients without an ITA graft was more than two-fold higher compared to these with single ITAs and more than three-fold higher compared to those with BITA grafting. CONCLUSIONS: Female gender, frequently associated with diabetes mellitus, presents a predictor for increased mortality in CABG. A discrimination of women with respect to a restriction of ITA grafting could be confirmed only for bilateral ITAs. The superior results of bilateral ITA grafts are independent of gender.

Aged↗
PubMed2001

Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection.

Early after infection, the retroviral RNA genome is reverse transcribed to generate a linear cDNA copy, then that copy is integrated into a chromosome of the host cell. We report that unintegrated viral cDNA is a substrate for the host cell non-homologous DNA end joining (NHEJ) pathway, which normally repairs cellular double-strand breaks by end ligation. NHEJ activity was found to be required for an end-ligation reaction that circularizes a portion of the unintegrated viral cDNA in infected cells. Consistent with this, the NHEJ proteins Ku70 and Ku80 were found to be bound to purified retroviral replication intermediates. Cells defective in NHEJ are known to undergo apoptosis in response to retroviral infection, a response that we show requires reverse transcription to form the cDNA genome but not subsequent integration. We propose that the double-strand ends present in unintegrated cDNA promote apoptosis, as is known to be the case for chromosomal double-strand breaks, and cDNA circularization removes the pro-apoptotic signal.

3T3 Cells↗
PubMed2001

Postictal diffusion-weighted imaging for the localization of focal epileptic areas in temporal lobe epilepsy.

PURPOSE: Diffusion-weighted MR imaging (DWI) is a novel technique to delineate focal areas of cytotoxic edema of various etiologies. We hypothesized that DWI may also detect the epileptogenic region and adjacent areas during the ictal and early postictal periods in patients with temporal lobe epilepsy (TLE). METHODS: We studied patients with intractable TLE (n = 9), due to hippocampal sclerosis (HS, n = 7), left mesial temporal lobe tumor (n = 1), and of unknown etiology (n = 1). Informed consent was obtained before inclusion in the study. All patients with single short seizures were scanned immediately after EEG-documented seizures (between 45 and 150 min); one of two patients in status was scanned 14 h after cessation of seizures. DWI results were analyzed visually and by calculating apparent diffusion coefficient (ADC) maps. RESULTS: We found significant decreases in ADC postictally in one of six patients with TLE due to HS and single short seizures. One patient with an incompletely resected temporal lobe tumor also exhibited ADC abnormalities. One patient in focal status epilepticus revealed a decrease in ADC, and one patient with a continuous aura had no DWI abnormality. CONCLUSIONS: Postictal DWI technique may occasionally help delineate epileptic areas in some patients with TLE. Yield is low in patients with HS and single short seizures: it may be higher in patients with tumor or status epilepticus.

Adolescent↗
PubMed2000

Antibody diversity: a link between switching and hypermutation.

Recent work indicates that mutations in a cytidine deaminase homologue ablate both immunoglobulin class switch recombination and somatic hypermutation. These findings now explain cases of autosomal hyper-IgM syndrome and reveal that critical components for key functions of B cells require RNA editing.

APOBEC-1 Deaminase↗
PubMed2000

Pediatric radiologists: who we are and what we do. Results of a membership survey of the Society for Pediatric Radiology--1999.

BACKGROUND: There is a need for reliable monitoring of workforce trends in the field of pediatric radiology by the Society for Pediatric Radiology. In addition, the Society should periodically assess itself as to its mission and relevance to its members via membership surveys. OBJECTIVE: The Membership Committee of the Society for Pediatric Radiology, 1999, conducted a 54-question survey to determine the makeup of its members, job profiles, satisfaction with services of the Society for Pediatric Radiology, and its official journal, Pediatric Radiology. MATERIALS AND METHODS: Seven hundred fifty surveys were given to active members of the Society for Pediatric Radiology in the United States and Canada. There were 275 surveys returned for an overall response of 37%. RESULTS: Mean age of members is 48 years with 99% of respondents working. Membership is 34% female and 66% male. Women members of the Society are younger (45 vs 49 years, P = 0.0012) and work less hours (47.8 vs 51.0, P = 0.0135) than men. Fifty-seven percent of respondents practice in a freestanding children's hospital, 29% in a "children's hospital within a hospital," and 14% are in community hospitals or an office-based practice. Eighty-two percent of the responding pediatric radiologist's time is spent in performing examination on children, with only 18% spent on adult work or administration. Forty-eight percent work at more than one office. Sixty-one percent worked evenings or weekends, excluding night call. Two hundred twenty-two of 275 respondents had received a Certificate of Added Qualification. The meeting "for CME credit" was considered the most important benefit of Society membership. Most respondents read select articles in Pediatric Radiology. There was sentiment to decrease esoteric case reports in favor of review articles. Only 19% of respondents submitted their articles to Pediatric Radiology initially. CONCLUSION: Pediatric radiologists are a diverse membership with the common goal of advocating for healthcare and imaging in children. Survey information given to the leadership of the Society will help the organization remain responsive to its members.

Adult↗
PubMed2000

Feasibility of instructing radiology technologists in the performance of gastrointestinal fluoroscopy.

OBJECTIVE: We sought to determine if dedicated gastrointestinal technologists could be trained to properly perform esophagography and double-contrast barium enema examinations. SUBJECTS AND METHODS: Ninety-four patients undergoing double-contrast barium enema examinations and 123 patients undergoing esophagographic examinations were included in the study. The study was conducted over a 4-month period, with examinations performed by eight gastrointestinal technologists, 10 radiology residents, and four staff radiologists. Four random lists were generated for each set of examinations. Each staff gastrointestinal radiologist, who was unaware of who had performed the examination, independently scored the representative radiographs. RESULTS: For the double-contrast barium enema examinations, no statistically significant differences were found between the technologists and residents for amount of barium used, degree of distention, cecal opacification, and quality of spot radiographs. The technologist-performed examinations had a statistically significant lower mean fluoroscopy time (3.2 min, compared with 4.0 min for staff radiologists and 5.7 min for residents). For the esophagrams, no statistically significant differences between technologists and residents were found for single-contrast esophagrams; radiographs of the gastric cardia; assessment of motility, reflux, and transit of a solid bolus; and fluoroscopy time. Double-contrast esophagrams obtained by technologists received a better mean score than did those of the residents. CONCLUSION: Radiology technologists can be trained to perform high-quality esophagography and double-contrast barium enema examinations without an unacceptably high radiation dose.

Adult↗
PubMed1999

Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. PLESS Study Group.

OBJECTIVES: Prostate-specific antigen (PSA) is produced exclusively in the prostate gland and is currently the most useful clinical marker for the detection of prostate cancer. In this report, we examine whether serum PSA is also a predictor of important benign prostatic hyperplasia (BPH)-related outcomes, acute urinary retention (AUR), and the need for BPH-related surgery. METHODS: Three thousand forty men were treated with either placebo or finasteride in a double-blind, randomized study of 4-year duration. Serum PSA was measured at baseline, and baseline prostate volume was measured in a 10% subset of 312 men. Probabilities and cumulative incidences of AUR and BPH-related surgery, as well as reduction in risk of events with finasteride, were calculated for the entire patient population, stratified by treatment assignment, baseline serum PSA, and prostate volume. RESULTS: The risk of either needing BPH-related surgery or developing AUR ranged from 8.9% to 22.0% during the 4 years in placebo-treated patients stratified by increasing prostate volume and from 7.8% to 19.9% when stratified by increasing serum PSA. In comparison with symptom scores, flow rates, and residual urine volume, receiver operating characteristic curve analyses showed that serum PSA and prostate volume were the most powerful predictors of spontaneous AUR in placebo-treated patients (area under the curve 0.70 and 0.81, respectively). Finasteride treatment reduced the relative risk of needing surgery or developing AUR by 50% to 74% and by 43% to 60% when stratified by increasing prostate volume and serum PSA, respectively. CONCLUSIONS: Serum PSA and prostate volume are powerful predictors of the risk of AUR and the need for BPH-related surgery in men with BPH. Knowledge of baseline serum PSA and/or prostate volume are useful tools to aid physicians and decision makers in predicting the risk of BPH-related outcomes and choosing therapy for BPH.

Acute Disease↗
PubMed1999

Synthetic dialysis shunts: thrombolysis with the Cragg thrombolytic brush catheter.

PURPOSE: To evaluate the effectiveness of the Cragg thrombolytic brush catheter for declotting of synthetic arteriovenous dialysis shunts. MATERIALS AND METHODS: In this randomized controlled trial, 77 patients with synthetic forearm loop shunts that were thrombosed were randomly assigned to undergo pharmacomechanical thrombolysis with a pulsed spray (n = 34) or a thrombolytic brush catheter (n = 43). The following findings were evaluated: declotting time, urokinase dose, procedure time, complications, and shunt patency at the first dialysis session and at 3 months. All data were collected prospectively in an unblinded manner. RESULTS: The total amount of urokinase used, including secondary interventions, was 243,657 IU with the catheter versus 476,563 IU with the pulsed spray (P = .001). At 15 minutes, clot lysis was successful in 66% of the patients with the catheter versus in 19% with the pulsed spray (P = .001). At 30 minutes, clot lysis was successful in 98% with the catheter versus 47% with the pulsed spray (P = .001). Procedure complication rates and patency at 3 months were similar for the catheter and the pulsed-spray groups. CONCLUSION: Use of the Cragg catheter with urokinase offered faster and more complete clot lysis than did use of the pulsed spray with urokinase. The amount of urokinase used with the catheter was half that used with the pulsed spray. Shunt patency at 3 months was similar for the two treatment methods.

Arteriovenous Shunt, Surgical↗
PubMed1999

Selenium-based digital radiography versus conventional film-screen radiography of the hands and feet: a subjective comparison.

OBJECTIVE: The purpose of this study was to subjectively compare the visibility of normal anatomy of the hands and feet using selenium-based digital radiography versus conventional film-screen (100-speed) radiography. SUBJECTS AND METHODS: Digital and film-screen images of the hands and feet of 24 patients were obtained without an antiscatter grid using identical X-ray exposure. Each pair of images was evaluated independently by five experienced radiologists for visibility of normal anatomy using a six-point rating scale. Soft tissues, cortical bone, and trabeculae were evaluated. For each observer, "equivalence" was defined as a mean difference in image quality of less than 1 unit on the 0-5 scale used in the study. Paired t tests were also performed to determine whether the average visibility rating of one technique was statistically superior to that of the other at a .05 level of significance for each observer and at each anatomic landmark. RESULTS: In all categories, selenium-based digital images were rated equivalent to film-screen images by the five observers. Using the sum of the nine landmarks, four of the five observers rated the quality of selenium-based digital images superior to that of film-screen images. CONCLUSION: Subjective visibility of normal anatomy of the hands and feet using selenium-based digital radiography was similar to that achieved using conventional film-screen radiography.

Aged↗
PubMed1999

Comparison of two barium suspensions for dedicated small-bowel series.

OBJECTIVE: The in vivo radiographic features of two commercially available formulations of barium used as contrast media in dedicated small-bowel series were compared. SUBJECTS AND METHODS: Fifty-six consecutive outpatients referred for a dedicated small-bowel series were randomly administered either E-Z-Paque or Entrobar. Representative survey radiographs from each examination were randomized and reviewed by six gastrointestinal radiologists from three institutions. Each observer assigned a numeric score (1 = poor, 2 = fair, 3 = good, and 4 = excellent) that rated the quality of the radiograph with respect to these characteristics: definition of fold pattern, translucency, distention, and integrity of the barium column. Statistical analysis was performed for each characteristic using Wilcoxon's two-sample rank sum test. RESULTS: All six observers found a statistically significant difference between the two barium formulations for mean scores for definition of fold pattern and translucency. Mean scores for fold pattern were 3.3, 3.0, 3.2, 3.6, 3.3, and 3.4 for Entrobar and 2.1, 2.3, 2.4, 3.2, 2.6, and 2.7 for E-Z-Paque. Mean scores for translucency were 2.5, 2.7, 2.8, 3.1, 2.7, and 3.3 for Entrobar and 1.6, 1.7, 2.1, 2.3, 1.9, and 2.7 for E-Z-Paque. No statistically significant difference was found for mean score for distention or integrity of the barium column. CONCLUSION: On radiographs, Entrobar was found to have superior characteristics for visualization of fold pattern and translucency but offered no advantages for distention or integrity of the barium column. Improved translucency and definition of fold pattern may translate into improved sensitivity and confidence in diagnosing small-bowel abnormality.

Barium Sulfate↗
PubMed1998

The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group.

BACKGROUND: Finasteride is known to improve urinary symptoms in men with benign prostatic hyperplasia, but the extent to which the benefit is sustained and whether finasteride reduces the incidence of related events, including the need for surgery and the development of acute urinary retention, is not known. METHODS: In this double-blind, randomized, placebo-controlled trial, we studied 3040 men with moderate-to-severe urinary symptoms and enlarged prostate glands who were treated daily with 5 mg of finasteride or placebo for four years. Symptom scores (on a scale of 1 to 34), urinary flow rates, and the occurrence of outcome events were assessed every four months in 3016 men. Prostate volume was measured in a subgroup of the men. Complete data on outcomes were available for 2760 men. RESULTS: During the four-year study period, 152 of the 1503 men in the placebo group (10 percent) and 69 of the 1513 men in the finasteride group (5 percent) underwent surgery for benign prostatic hyperplasia (reduction in risk with finasteride, 55 percent; 95 percent confidence interval, 41 to 65 percent). Acute urinary retention developed in 99 men (7 percent) in the placebo group and 42 men (3 percent) in the finasteride group (reduction in risk with finasteride, 57 percent; 95 percent confidence interval, 40 to 69 percent). Among the men who completed the study, the mean decreases in the symptom score were 3.3 in the finasteride group and 1.3 in the placebo group (P<0.001). Treatment with finasteride also significantly improved urinary flow rates and reduced prostate volume (P<0.001). CONCLUSIONS: Among men with symptoms of urinary obstruction and prostatic enlargement, treatment with finasteride for four years reduces symptoms and prostate volume, increases the urinary flow rate, and reduces the risk of surgery and acute urinary retention.

5-alpha Reductase Inhibitors↗
PubMed1998

Parathyroid detection in secondary hyperparathyroidism with 123I/99mTc-sestamibi subtraction single photon emission computed tomography.

123I/99mTc-sestamibi subtraction single photon emission computed tomography (SPECT) has been proposed to detect hyperplastic parathyroid tissue, but the clinical usefulness of this technique in secondary hyperparathyroidism is uncertain. The purpose of this study was to evaluate preoperative parathyroid localization using 123I/99mTc-sestamibi subtraction SPECT in patients with renal failure and secondary hyperparathyroidism. Nineteen patients with chronic renal failure and secondary hyperparathyroidism underwent 123I/99mTc-sestamibi subtraction SPECT imaging preoperatively. None of these patients had undergone previous neck surgery. The location, weight, and histopathological results of all identified parathyroid glands were recorded. Surgery was considered successful in all patients, with resection of a total of 74 hyperplastic parathyroid glands. 123I/99mTc-sestamibi subtraction SPECT correctly identified 57 of these parathyroid glands (77% sensitivity). The mean weight among the true positive glands (n = 57) was 1031 mg (range, 45-7900 mg), and that among the false negative glands (n = 17) was 465 mg (range, 20-1800 mg). This difference between the mean weights was statistically significant (P = 0.018). There was a positive correlation between parathyroid weight and detectability with 123I/99mTc-sestamibi subtraction SPECT (Spearman correlation = 0.28; P = 0.0167). 123I/99mTc-sestamibi subtraction SPECT is able to correctly localize hyperplastic parathyroid glands in patients with renal failure and secondary hyperparathyroidism, but there is a fairly weak relationship between preoperative detection rate and anatomical parathyroid gland size.

Adenoma↗
PubMed1998

Prognostic significance of allelic imbalance of chromosome arms 7q, 8p, 16q, and 18q in stage T3N0M0 prostate cancer.

Frequent allelic imbalance of polymorphic markers mapped to regions of the 7q, 8p, 16q, and 18q arms has been reported in prostate cancer. To better define the clinical significance of these genetic alterations, we undertook a retrospective analysis of systemic progression and survival in patients with a single stage of prostate cancer. We ascertained all 227 patients from the Mayo Clinic Radical Prostatectomy Registry who had a histologic high-grade, pathologic stage C (pT3N0M0) tumor surgically removed between 1966 and 1987. The mean follow-up of this population of patients was 7.7 years. DNAs were extracted from cancer lesions identified in 5-micron paraffin-embedded tumor sections. Control DNAs were obtained from surgically removed lymph nodes. Paired DNA samples of 153 patients were available for analysis using 16 polymorphic microsatellite markers mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22. The frequencies of allelic imbalance for at least one marker mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22 were 30, 58, 53, and 45% of all informative cases, respectively. Allelic imbalance at 7q31 strongly correlated with systemic cancer progression and to a slightly lesser extent with cancer-specific death. Eight-year systemic cancer progression-free rates were 58 and 81% for cases with and without 7q31 allelic imbalance, respectively (P < 0.001). Eight-year prostate cancer-specific survival rates were 70 and 85% with and without 7q31 allelic imbalance, respectively (P = 0.019). Multivariate analysis indicated that allelic imbalance at 7q31 is a significant independent predictor of systemic progression (P < 0.001) and possibly prostate cancer death (P = 0.029). In addition, allelic imbalance of the specific loci D7S522 (7q31.1) and D8S258 (8p22-p21.3) was strongly associated with systemic progression (P < 0.001 and P = 0.010, respectively) and with prostate cancer death (P < 0.001 and P = 0.009, respectively). The results suggest that a gene or genes mapped to 7q31.1 and possibly 8p22-p21.3 play an important role in tumor progression, and that allelic imbalances at these regions are markers for poor prognosis in prostate carcinoma.

Aged↗