Methylidene-imidazolone (MIO) from histidine and phenylalanine ammonia-lyase.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Biomedical subjects
B Langer
Publications and source records attributed to B Langer.
[Tetralogy of Fallot in monozygotic twins].
UNLABELLED: The causative mechanisms of congenital heart defects remain unclear and little is known about the respective implication of chance, genetics and environment, though recent findings in molecular biology may provide further insight into understanding the pathophysiologic basis of congenital heart diseases. CASE REPORT: We report the exceptional but significant case of monozygotic twins both affected by tetralogy of Fallot, for whom prenatal diagnosis ruled out 22q11 microdeletion. CONCLUSION: We discuss how far this observation is consistent with the latest hypothesis, which emphasizes the leading role of genetic factors. Several genes indeed, either separately or in combination, could be responsible for those defects, even if other influences may still come into play.
Chromosomes, Human, Pair 22↗
Characterization of the active site of histidine ammonia-lyase from Pseudomonas putida.
Elucidation of the 3D structure of histidine ammonia-lyase (HAL, EC 4.3.1.3) from Pseudomonas putida by X-ray crystallography revealed that the electrophilic prosthetic group at the active site is 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) [Schwede, T.F., Rétey, J., Schulz, G.E. (1999) Biochemistry, 38, 5355-5361]. To evaluate the importance of several amino-acid residues at the active site for substrate binding and catalysis, we mutated the following amino-acid codons in the HAL gene: R283, Y53, Y280, E414, Q277, F329, N195 and H83. Kinetic measurements with the overexpressed mutants showed that all mutations resulted in a decrease of catalytic activity. The mutants R283I, R283K and N195A were approximately 1640, 20 and 1000 times less active, respectively, compared to the single mutant C273A, into which all mutations were introduced. Mutants Y280F, F329A and Q277A exhibited approximately 55, 100 and 125 times lower activity, respectively. The greatest loss of activity shown was in the HAL mutants Y53F, E414Q, H83L and E414A, the last being more than 20 900-fold less active than the single mutant C273A, while H83L was 18 000-fold less active than mutant C273A. We propose that the carboxylate group of E414 plays an important role as a base in catalysis. To investigate a possible participation of active site amino acids in the formation of MIO, we used the chromophore formation upon treatment of HAL with l-cysteine and dioxygen at pH 10.5 as an indicator. All mutants, except F329A showed the formation of a 338-nm chromophore arising from a modified MIO group. The UV difference spectra of HAL mutant F329A with the MIO-free mutant S143A provide evidence for the presence of a MIO group in HAL mutant F329A also. For modelling of the substrate arrangement within the active site and protonation state of MIO, theoretical calculations were performed.
Catalytic Domain↗
Resection of hepatocellular carcinoma without preoperative tumor biopsy.
OBJECTIVE: To evaluate the need for a preoperative tumor biopsy of liver lesions suspicious for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: With advances in liver imaging, the results of recent studies have suggested a very high accuracy of preoperative evaluation of liver masses suspicious of HCC, making preoperative tumor biopsy unnecessary. METHODS: A retrospective analysis was conducted of all liver resections for HCC at the Toronto General and Mt. Sinai Hospitals, Toronto, between October 1994 and December 1998. RESULTS: Sixty patients underwent 65 liver resections without a preoperative liver biopsy. The median age was 61 years. Sixty percent of the patients had cirrhosis and 38.5% had noncirrhotic chronic hepatitis. HCC was confirmed histologically in the surgical specimen in 63 of the 65 cases (96.9%). Both patients without HCC had a significant risk factor for HCC (chronic hepatitis C and alcohol in one and chronic hepatitis B and previous resection for HCC in the other). The lesions were 2 cm and 2.7 cm in diameter, and the alpha-fetoprotein level was low (<5 and 22 ng/mL, respectively). In such patients, with tumor 3 cm or smaller and an alpha-fetoprotein level less than 100 ng/mL (10 patients), the false-positive rate for the preoperative diagnosis was 2/10 (20%). CONCLUSIONS: Preoperative diagnosis of HCC was highly accurate in lesions larger than 3 cm. Tumor biopsy is unnecessary in these patients. However, in a subgroup of patients with lesions less than 3 cm, particularly those with alpha-fetoprotein levels less than 100 ng/mL, there is a higher false-positive diagnostic rate, and tumor biopsy should be considered.
Adult↗
[Multiple gastrointestinal tract duplication : a neonatal case report].
We report the case of newborn with multiple GI tract duplication cysts. Prenatal diagnosis was that of duodenal stenosis. A complete screening for polymalformative syndrome is required in the neonatal period and the authors insist on the importance of US and color Doppler US imaging.
Abnormalities, Multiple↗
Sudden interchannel interaction in the Tl 6p ionization above the 5d threshold
The linear magnetic dichroism in the angular distribution of Tl 5d and 6p photoelectrons and their dynamical spin polarization have been measured between hnu = 30 and 50 eV. In contrast to the Xe 5p photoionization at the 4d threshold, our results show that above the Tl 5d threshold strong interchannel coupling effects induce a sudden increase in the asymptotic phase difference of the s and d waves for the Tl 6p ionization. This shows that the valence excitation is different for resonant (Xe 4d) and nonresonant (Tl 5d) excitation from subvalence shells.
Journal Article↗
Hepatic resection of noncolorectal nonneuroendocrine metastases.
Because hepatic resection is generally a safe procedure, the indications for resection of noncolorectal nonneuroendocrine (NCNNE) hepatic metastases have broadened. The prognostic features of NCNNE metastases treated surgically were reviewed to define better the value of resection. A retrospective review of patients undergoing liver resection for NCNNE metastases between 1978 and 1998 was undertaken. Thirty-seven patients were identified. Mean age was 56 years, with a median follow-up of 22 months. Primary tumor sites were grouped into gastrointestinal (GI) adenocarcinoma (small bowel, n = 4; pancreas, n = 2; esophagus, n = 1) and other (renal cell, n = 7; sarcoma, n = 7; melanoma, n = 5; adrenal, n = 3; unknown adenocarcinoma, n = 3; thyroid, n = 2; testicular, n = 1; ovarian, n = 1; breast, n = 1). All patients underwent surgery for cure. Metastases were synchronous in 14 patients. There was no surgical mortality. Overall 5-year survival rate was 45%. Five-year survival rates were better for patients with non-GI-origin metastases (60% v 0%; P =.01). Long-term survival was seen only in patients with non-GI-origin metastases. The extent of resection, presence of synchronous metastases, or disease-free interval from time of original disease to presentation with liver metastases were not predictive of outcome. We conclude that patients with NCNNE hepatic metastases can undergo liver resection with an expectation of prolonged survival. However, patients with liver metastases from GI primary tumors other than the colorectum are unlikely to show extended survival.
Adenocarcinoma↗
Fetal pyelectasis.
Explore the source record for details and available documents.
Congenital Abnormalities↗
Distinct internalization of M2 muscarinic acetylcholine receptors confers selective and long-lasting desensitization of signaling to phospholipase C.
Although M1-M4 muscarinic acetylcholine receptors (mAChRs) in HEK-293 cells internalize on agonist stimulation, only M1, M3, and M4 but not M2 mAChRs recycle to the plasma membrane. To investigate the functional consequences of this phenomenon, we compared desensitization and resensitization of M2 versus M4 mAChRs. Treatment with 1 mM carbachol for 1 h at 37 degrees C reduced numbers of cell surface M2 and M4 mAChRs by 40-50% and M2 and M4 mAChR-mediated inhibition of adenylyl cyclase, intracellular Ca2+ concentration ([Ca2+]i) increases, and phospholipase C (PLC) activation by 60-70%. Receptor-mediated inhibition of adenylyl cyclase and [Ca2+]i increases significantly resensitized within 3 h. However, M4 but not M2 mAChR-mediated PLC activation resensitized. At 16 degrees C, M2 mAChR-mediated [Ca2+]i increases and PLC stimulation desensitized to a similar extent as at 37 degrees C. However, at 16 degrees C, where M2 mAChR internalization is negligible, both M2 mAChR responses resensitized, demonstrating that M2 mAChR resensitization proceeds at the plasma membrane. Examination of M2 mAChR responses following inactivation of cell surface mAChRs by quinuclidinyl benzilate revealed substantial receptor reserve for coupling to [Ca2+]i increases but not to PLC. We conclude that M2 mAChR internalization induces long-lasting PLC desensitization predominantly because receptor loss is not compensated for by receptor recycling or receptor reserve.
Calcium↗
Biliary stenting versus bypass surgery for the palliation of malignant distal bile duct obstruction: a meta-analysis.
The objective of this analysis is to compare endoscopic stenting with surgical bypass in patients with unresectable, malignant, distal common bile duct obstruction using the technique of meta-analysis. The inclusion criteria for the studies were randomized patient assignment, publication in the English language, 20 or more patients per group, all patients followed up until death, and follow-up and complications reported in an equivalent way for both treatment arms. Data extraction was performed independently by 2 of the authors. The number of treatment failures, serious complications, requirement for additional treatment sessions, and 30-day mortality were extracted. Three existing trials met the inclusion criteria, all of which compared surgery with the use of plastic stents. There were no studies identified that used metallic expandable stents. For the rate of treatment failure and serious complications, the odds ratios (ORs) of the 3 trials were heterogeneous, and no summary ORs were calculated. More treatment sessions were required after stent placement than after surgery, and a common OR was estimated to be 7.23 (95% confidence interval [CI], 3.73 to 13.98). Thirty-day mortality was not significantly different (OR = 0.522; 95% CI, 0.263 to 1.036). Although surgical bypass required fewer additional treatment sessions, existing data do not allow a definitive conclusion on which treatment is preferable. A larger randomized controlled trial using newer metallic stents and proper quality-of-life instruments is required.
Cholestasis↗
Congenital cholesteatoma and cholesterol granuloma of the temporal bone: role of magnetic resonance imaging.
Magnetic resonance imaging (MRI) can be of significant benefit in characterizing expansile lesions of the petrous apex. MRI can be of particular help in distinguishing congenital cholesteatoma from cholesterol granuloma. Furthermore, with the advent of faster high-resolution scanning techniques, MRI can define precise spatial relationships of these masses with the middle and inner ear structures, internal carotid artery, jugular vein, and other structures of the skull base. MRI scanning is sensitive in detecting intracranial extension of these masses. MR angiography can provide additional information regarding the relationship of these masses with adjacent vascular structures and confirm patency of the adjacent vessels. In the postoperative period, MR scanning can help evaluate for complete removal, complication, recurrence, or formation of complicating granulation tissue.
Bone Diseases↗
Re: A comparison of endosseous dental implant surfaces. Cochran DL (1999;70:1523-1539).
Explore the source record for details and available documents.
Dental Implantation, Endosseous↗
[Bone marrow cellularity in acute lymphoblastic leukemia of children].
The early response to therapy in childhood acute lymphoblastic leukemia (ALL) is typically assessed by bone marrow status. The clearance of blast cells in peripheral blood and bone marrow during induction therapy was analysed in 38 children (27 precursor-B-ALL and 11 precursor T-ALL) treated according to BFM90 or New York 93 protocols. Leukocyte count and peripheral blood smear taken at diagnosis, day 8, day 14 and day 33 as well as bone marrow cellularity and percentage of blasts on days: 0, 14, 33 were analysed. The number of blasts in bone marrow was correlated to bone marrow cellularity (Spearman's rho = 0.72, p = 0.001). Patients with T-ALL were more frequently resistant to steroids in vivo and reached remission later in comparison to precursor-B-ALL children (p = 0.019), however blasts reduction ratio was comparable in both lineages. Bone marrow cellularity on days 14 and 33 of induction therapy was similar.
Adolescent↗
Physicians' attitudes towards health telematics--an empirical survey.
Telemedical networks and services have received high attention in professional and scientific media in the recent past. In Germany some institutions and few physicians volunteer in experimenting with diverse telemedical service offerings. However, much is speculated but little is known about attitudes and expectations of the majority of physicians in local offices towards this new medium. Therefore we conducted an empirical survey using a random regional sample to poll the respective opinions. Encouraged by a high response rate to our paper questionnaire, we offer as conclusion: that physicians are surprisingly realistic about costs and benefits and can therefore be expected to subscribe as soon as benefits become obvious; that this trend increases with offices being taken over or newly established by younger physicians; and that the establishment of networks of comprehensive care offered by health care professionals from different disciplines is regarded as essential future advantage of telemedical networks.
Adult↗
Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening.
BACKGROUND AND METHODS: There are few data on the prevalence and clinical outcome of hepatitis C infection in children. We studied 458 children who underwent cardiac surgery in Munich, Germany, before 1991, when blood-donor screening for hepatitis C was introduced in Germany. Their mean age at first operation was 2.8 years; none of the children had received blood transfusions before or 'after cardiac surgery, and none of their mothers had antibodies to the hepatitis C virus (anti-HCV). We compared these patients with 458 control subjects matched for age and sex. RESULTS: Sixty-seven (14.6 percent) of the 458 patients who had undergone cardiac surgery had anti-HCV, as compared with 3 (0.7 percent) of the control subjects (P<0.001). At a mean interval of 19.8 years after the first operation, 37 (55 percent) of the 67 patients who were positive for anti-HCV had detectable HCV RNA in their blood. The infection had cleared in the other 30 patients, as evidenced by negative results on three polymerase-chain-reaction analyses performed at six-month intervals. Only 1 of the 37 patients who were positive for HCV RNA had elevated levels of liver enzymes; that patient had severe right-sided congestive heart failure. Of the 17 patients who underwent liver biopsies, only 3 had histologic signs of progressive liver damage. These three patients had additional risk factors: two had congestive heart failure, and the third had also been infected with hepatitis B virus. CONCLUSIONS: Children who had undergone cardiac surgery in Germany before the implementation of blood-donor screening for hepatitis C had a substantial risk of acquiring the infection. However, after about 20 years, the virus had spontaneously cleared in many patients. The clinical course in those still infected seems more benign than would be expected in people infected as adults.
Adult↗
Influence of hospital volume on mortality following major cancer surgery.
Explore the source record for details and available documents.
Hospital Mortality↗
Relation between hospital surgical volume and outcome for pancreatic resection for neoplasm in a publicly funded health care system.
BACKGROUND: Recent studies from the United States have shown that institutions with higher numbers of pancreatic resection procedures for neoplasm have lower mortality rates associated with this procedure. However, minimal work has been done to assess whether the results of similar volume-outcome studies within a publicly financed health care system would differ from those obtained in a mixed public-private health care system. METHODS: A population-based retrospective analysis was used to examine pancreatic resection for neoplasm in Ontario for the period 1988/89 to 1994/95. Outcomes examined included in-hospital case fatality rate and mean length of stay in hospital. For each hospital, total procedure volume for the study period was defined as low (fewer than 22), medium (22-42) or high (more than 42). Regression models were used to measure volume-outcome relations. RESULTS: The likelihood of postoperative death was higher in low-volume and medium-volume centres than in high-volume centres (odds ratio 5.1 and 4.5 respectively; p < 0.01 for both). Mean length of stay was greater in low- and medium-volume centres than in high-volume centres (by 7.7 and 9.2 days respectively, p < 0.01 for both). INTERPRETATION: This study adds to growing evidence that, for pancreatic resection for neoplasm, patients may have better outcomes if they are treated in high-volume hospitals rather than low-volume hospitals.
Aged↗