Statistical monitoring of the dental practice.
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Data Interpretation, Statistical↗
Biomedical subjects
S Schwartz
Publications and source records attributed to S Schwartz.
Modification of organ protein synthesis after surgical stress by low energy diets with different supplements.
We have studied the effects of hypocaloric diets with different supplements on liver and jejunal mucosa protein synthesis. The supplements assayed were medium chain triglycerides (diet MCT, with 50% carbohydrates: 25% long chain triglycerides (LCT): 25% medium chain triglycerides (MCT), standard amino acids), branched-chain amino acids (diet BCA, identical to control diet L50, with 15.3% of nitrogen replaced by branched-chain amino acids) and glutamine (diet GLN, identical to diet L50, with 15.3% of nitrogen replaced by glutamine). The control diet (L50) had 50% carbohydrates: 50% LCT and standard amino acids. The diets were assayed on 86 rats with femoral fracture immobilized by Kirschner pin insertion. Nutrition was administered for 4 days. On the fifth day, liver and jejunal mucosa protein synthesis was determined. A branched-chain amino acid supply in a proportion higher than 21.2% of amino acid nitrogen significantly decreased liver and jejunal mucosa protein synthesis, while the same amount of glutamine did not modify it. MCT had no effect on jejunal mucosa protein synthesis, while it was decreased significantly in the liver.
Amino Acids, Branched-Chain↗
Modification of organ protein synthesis after surgical stress by low energy diets with different lipid/glucose ratios.
The aim of this work was to study the effects of low energy parenteral diets with different lipid/glucose ratios on rat liver and jejunal mucosa protein synthesis. The studied diets were: L0 (100% glucose, control diet), L25 (25% lipids: 75% glucose), L50 (50% lipids: 50% glucose) and L75 (75% lipids: 25 % glucose). All diets were isoenergetic and isonitrogenated, with a standard amino acid content. The diets were assayed in 93 rats with open femoral fracture immobilized by Kirschner pin insertion. The diets were administered for 4 days. On the fifth day, liver and jejunal mucosa protein synthesis were determined. Highest liver protein synthesis rates were obtained with the diet compositions: lipid/carbohydrate ratio: 25% lipids and 75% carbohydrates (expressed as energy ratio). A higher proportion of lipids significantly decreases liver protein synthesis (p <0.05). Jejunal mucosa protein synthesis followed the same pattern, with the same statistical differences.
Animals↗
Toward quality assurance for metaphase FISH: a multicenter experience.
Although fluorescent in situ hybridization (FISH) is rapidly becoming a part of clinical cytogenetics, no organization sponsors multicenter determinations of the efficacy of probes. We report on 23 laboratories that volunteered to provide slides and to use a probe for small nuclear ribonucleoprotein polypeptide N (SNRPN) and a control locus. Experiences with FISH for these laboratories during 1994 ranged from 0 to 645 utilizations (median = 84) involving blood, amniotic fluid, and bone marrow. In an initial study of hybridization efficiency, the median percentage of metaphases from normal individuals showing two SNRPN and two control signals for slides prepared at each site was 97.0 (range = 74-100); for slides prepared by a central laboratory, it was 97.8 (range = 81.6-100). In a subsequent blind study, each laboratory attempted to score 5 metaphases from each of 23 specimens [8 with del(15)(q11.2-->q12) and 15 with normal #15 chromosomes]. Of 529 challenges, the correct SNRPN pattern was found in 5 of 5 metaphases in 457 (86%) and in 4 of 5 in 33 (6%). Ambiguous, incomplete, or no results were reported for 32 (6%) challenges. Seven (1%) diagnostic errors were made, including 6 false positives and 1 false negative: 1 laboratory made 3 errors, 1 made 2, and 2 made 1 each. Most errors and inconsistencies seemed due to inexperience with FISH. The working time to process and analyze slides singly averaged 49.5 min; slides processed in batches of 4 and analyzed singly required 36.9 min. We conclude that proficiency testing for FISH by using an extensive array of challenges is possible and that multiple centers can collaborate to test probes and to evaluate costs.
Autoantigens↗
Toward quality assurance for metaphase FISH: a multi-center experience.
Although fluorescent in situ hybridization (FISH) is rapidly becoming a part of clinical cytogenetics, no organization sponsors multi-center determinations of the efficacy of probes. We report on 23 laboratories that volunteered to provide slides and to use a probe for SNRPN and a control locus. Experiences with FISH for these laboratories during 1994 ranged from 0 to 645 utilizations (median = 84) involving blood, amniotic fluid and bone marrow. In an initial study of hybridization efficiency, the median percentage of metaphases from normal individuals showing two SNRPN and 2 control signals for slides prepared at each site was 97.0 (range = 74-100); for slides prepared by a central laboratory, it was 97.8 (range = 81.6-100). In a subsequent blind study, each laboratory attempted to score 5 metaphases from each of 23 specimens [8 with del(15) (q11.2-->q12) and 15 with normal 15 chromosomes]. Of 529 challenges, the correct SNRPN pattern was found in 5 of 5 metaphases in 457 (86%) and in 4 of 5 in 33 (6%). Ambiguous, incomplete or no results were reported for 32 (6%) challenges. Seven (1%) diagnostic errors were made including 6 false positives and 1 false negative: 1 laboratory made 3 errors, 1 made 2, and 2 made 1 each. Most errors and inconsistencies seemed due to inexperience with FISH. The working time to process and analyze slides singly averaged 49.5 minutes; slides processed in batches of 4 and analyzed singly required 36.9 minutes. We conclude that proficiency testing for FISH using an extensive array of challenges is possible and that multiple centers can collaborate to test probes and to evaluate costs.
Humans↗
Activated N-ras oncogene and N-ras proto-oncogene act through the same pathway for in vivo tumorigenesis.
We compared the tumorigenic effects of the N-ras oncogene and the N-ras proto-oncogene in lymphoid and mammary tissues in an in vivo model. For this purpose, we generated transgenic mice with high levels of N-ras oncogene or N-ras proto-oncogene expression, driven by the complete mouse mammary tumor virus LTR (MMTV-LTR) (MMTV/N-rasT and MMTV/N-rasN constructs) and transgenic mice with low levels of N-ras oncogene or N-ras proto-oncogene expression, driven by a truncated MMTV-LTR (TMTV/N-rasT and TMTV/N-rasN constructs). We show that both, the N-ras proto-oncogene and the N-ras oncogene with a C:G-->A:T mutation at codon 61, lead to identical tumor types: lymphoblastic T-cell lymphomas, cleaved B-cell lymphomas and poorly differentiated mammary carcinomas. Nevertheless, there were quantitative differences in tumor incidence and latency and in transgene expression among N-ras oncogene and N-ras proto-oncogene transgenics. Despite these differences in tumor kinetics, the predisposition to identical tumor types is in agreement with the idea that the N-ras oncogene and the N-ras proto-oncogene act through the same pathway for in vivo tumorigenesis in B-cells, T-cells or mammary epithelial cells.
Animals↗
CWR22: the first human prostate cancer xenograft with strongly androgen-dependent and relapsed strains both in vivo and in soft agar.
Most patients' prostate cancers respond to androgen deprivation but relapse after periods of several months to years. Only two prostate cancer xenografts, LNCaP and PC-346, have been reported to be responsive to androgen deprivation and to relapse subsequently. Both of these tumors shrink slightly, if at all, and relapse less than 5 weeks after androgen withdrawal. After androgen withdrawal, the human primary prostate cancer xenograft CWR22 regresses markedly, and prostate-specific antigen (PSA) falls up to 3000-fold in the blood of mice. PSA usually returns to normal. In some animals, the tumor relapses and is then designated CWR22R. In these animals, PSA starts to rise approximately 2-7 months, and tumor begins to grow 3-10 months after castration. Animals with CWR22 need to be euthanized because of large tumors 6-12 weeks after the transplantation of CWR22. Androgen withdrawal prolongs life approximately 3-4-fold.
Agar↗
Congenital central hypoventilation syndrome: mutation analysis of the receptor tyrosine kinase RET.
Congenital central hypoventilation syndrome (CCHS) usually occurs as an isolated phenotype. However, 16% of the index cases are also affected with Hirschsprung disease (HSCR). Complex segregation analysis suggests that CCHS is familial and has the same inheritance pattern with or without HSCR. We postulate that alteration of normal function of the receptor tyrosine kinase, RET, may contribute to CCHS based on RET's expression pattern and the identification of RET mutations in HSCR patients. To further explore the nature of the inheritance of CCHS, we have undertaken two main routes of investigation: cytogenetic analysis and mutation detection. Cytogenetic analysis of metaphase chromosomes showed normal karyotypes in 13 of the 14 evaluated index cases; one index case carried a familial pericentric inversion on chromosome 2. Mutation analysis showed no sequence changes unique to index cases, as compared to control individuals, and as studied by single strand conformational polymorphism (SSCP) analysis of the coding region of RET. We conclude that point mutations in the RET coding region cannot account for a substantial fraction of CCHS in this patient population, and that other candidate genes involved in neural crest cell differentiation and development must be considered.
Child↗
Animal behavior case of the month. A cat was referred for evaluation of self-mutilation.
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Animals↗
Cytogenetic and molecular genetic characterization of trisomy 20 mosaicism in fetal blood and tissues.
We report a case of mosaic trisomy 20, the most common autosomal mosaicism identified in amniocytes, ascertained in a woman referred for amniocentesis because of abnormal ultrasound at 18.1 weeks' gestation which revealed short femurs and nuchal thickening. Metaphase analysis of 98 clones revealed 47,XY, +20 in 96 cells (98 per cent). Trisomy 20 was demonstrated in 6 cells (12 per cent) in a total of 50 cells from two fetal blood cultures obtained after pregnancy termination. Fluorescence in situ hybridization (FISH) analysis of interphase nuclei utilizing a chromosome 20 alpha-satellite centromeric DNA probe revealed three signals in 57/546 nuclei (10 per cent) in fetal blood. Metaphase analysis of 167 cells from seven different fetal tissue sources revealed trisomy 20 in 32 cells (19.2 per cent). The percentage of trisomy 20 cells varied with tissue type, with the highest percentage (13/25 cells, 52 per cent) identified in the small intestine and lymph nodes and the lowest percentage (1/34 cells, 2.9 per cent) identified in a specimen of chorionic villi. Molecular genetic analyses utilizing polymerase chain reaction (PCR)-formated dinucleotide repeat polymorphisms demonstrated that the non-disjunctional event most likely occurred post-zygotically and that the origin of the extra chromosome 20 was maternal. This study is the first to demonstrate trisomy 20 cells in fetal blood, suggesting that mosaic trisomy 20 can be embryonic in origin. In cases of prenatally detected mosaic trisomy 20, examination of fetal blood should be considered, as well as study of placental membranes, skin, and urine sediment to confirm the karyotype and determine its significance.
Adult↗
Centromeres of human chromosomes.
The centromere, recognized cytologically as the primary constriction, is essential for chromosomal attachment to the spindle and for proper segregation of mitotic and meiotic chromosomes. Considerable progress has been made in identifying both DNA and protein components of the centromere and kinetochore complex in mammalian chromosomes, including definition of specific motor proteins with demonstrable functions in chromosome movement. Searches for possible environmental influences on chromosome disjunction might logically be based on known components of the segregation apparatus, both intrinsic and extrinsic to the chromosomes themselves. This article reviews available information on both DNA and protein components of the centromere of mammalian, particularly human, chromosomes and summarizes our current understanding of their role(s) in facilitating normal chromosome behavior in mitosis and meiosis.
Animals↗
Effect of 14 days' subcutaneous administration of the human amylin analogue, pramlintide (AC137), on an intravenous insulin challenge and response to a standard liquid meal in patients with IDDM.
Individuals with insulin-dependent diabetes mellitus (IDDM or type 1 diabetes) are deficient in both insulin and amylin, peptides secreted by the beta cell. We have investigated the effects of amylin replacement therapy employing the human amylin analogue, pramlintide (25, 28, 29-pro-human amylin, previously referred to as AC137), upon the responses to a standardized insulin infusion (40 mU. kg-1. h-1) for 100 min and a liquid Sustacal meal (360 kcal) in 84 healthy IDDM patients. Following baseline evaluations, patients were randomly assigned to receive subcutaneous injections of placebo, 30, 100 or 300 micrograms pramlintide 30 min before meals for 14 days. There was no meaningful difference between adverse events reported by the 30-micrograms pramlintide and the placebo groups, but ten subjects withdrew due to nausea, eight of these in the 300-micrograms dose group. Peak plasma pramlintide concentrations for the 30-micrograms group were 21 +/- 3 and 29 +/- 5 pmol/l on Days 1 and 14, respectively. These values are similar to postprandial plasma amylin concentrations in normal volunteers. The plasma glucose, free insulin, glucagon, epinephrine and norepinephrine concentrations during the insulin infusion test before and after therapy were identical in each of the group. Prior to pramlintide therapy, Sustacal ingestion produced a 4.0-4.8 mmol/l rise in plasma glucose concentrations in each of the groups. Pramlintide therapy reduced postprandial hyperglycaemia as reflected by the 3-h incremental AUCglucose (AUCglucose above or below fasting glucose concentration) Day 1 vs Day 14: 30 micrograms, 322 +/- 92 vs -38 +/- 161 mmol/l.min, p = 0.010; 100 micrograms, 317 +/- 92 vs -39 +/- 76 mmol/l.min, p = 0.001; and 300 micrograms, 268 +/- 96 vs -245 +/- 189 mmol/l.min, p = 0.077. Thus, pramlintide therapy with these regimens did not appear to impair either in vivo insulin action or the counter-regulatory response to hypoglycaemia but did show a clear effect of blunting postprandial hyperglycaemia following a standardized meal.
Adolescent↗
[2 unusual cutaneous T-cell lymphomas with extracutaneous involvement].
In this paper we present two patients with T-cell lymphomas, who presented with unique skin lesions, but later developed extracutaneous involvement. The first patient showed marked edematous infiltration of the trunk and legs as well as grouped, umbilicated red-to-blue papules limited to the body folds. The second patient had lesions reminiscent of poikiloderma vascular atrophicans, with erythema, teleangiectasia, hypo- and hyperpigmentation, and bizarre scarring, followed by development of papules and nodules. The first patient also had marked leukocytosis and lymph node enlargement. Histology, immunohistology, and immunophenotyping revealed an unclassifiable CD8+, alpha, beta +, CD10+ cutaneous T cell lymphoma with leukemic involvement. Unclassifiable cutaneous T-cell lymphoma was also diagnosed in the second patient: it was associated with a monoclonal proliferation of T-cell receptor V gamma 9, delta + large granular T lymphocytes and finally developed into frank, acute pre-T lymphatic leukemia.
Adult↗
Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia.
The clinical and biological significance of additional chromosome aberrations was investigated in a large series of 66 adult patients with Philadelphia (Ph) chromosome positive acute lymphoblastic leukaemia (ALL). Additional chromosome changes were observed in 71% of the cases. 9p abnormalities were identified in 26%, and monosomy 7 as well as hyperdiploid karyotypes 50 were both found in 17% of cases. 9p anomalies were characterized by a low complete remission (CR) rate (58%) and an extremely short median remission duration (MRD: 100 d). In patients with monosomy 7, the poor treatment outcome was confirmed (CR rate 55%: MRD 113 d). In contrast, all patients with hyperdiploid karyotypes 50 achieved CR, and the overall survival was superior to all other Ph-positive ALL patients except those without additional chromosome aberrations. Exclusive rearrangement of the minor breakpoint cluster region of the BCR gene and lack of coexpression of myeloid-associated antigens in cases with 9p anomalies as well as a high frequency of rearrangements of the major breakpoint cluster region of the BCR gene in patients with monosomy 7 (89%) further substantiated that additional chromosome aberrations may characterize distinct subgroups of Ph-positive ALL. Moreover, the necessity of the complementing use of chromosome banding analyses, polymerase chain reaction (PCR) assays, and fluorescence in situ hybridizations in the accurate identification of Ph-positive patients has become evident due to variant Ph translocations in 3%, and negative PCR assays in 4% of the cases.
Adolescent↗
Comparison of centralized versus "site-based" measurement of angiographic stenosis for eligibility in the asymptomatic carotid atherosclerosis study.
RATIONALE AND OBJECTIVES: The authors determine the reliability of centralized versus noncentralized (site-based) measurement of angiographic stenosis of patients enrolled into the multicenter, prospective, Asymptomatic Carotid Atherosclerosis Study by angiographic studies. METHODS: Percent agreements and correlations of 244 masked and prospectively interpreted angiograms were calculated for comparison of centralized and noncentralized readers measuring the percent carotid stenosis from the same angiographic studies. Univariate summary statistics for differences in percent stenoses were calculated for these readings. RESULTS: Agreement between readings were 88.5% and 91.8% with kappa statistics of 0.77 and 0.73 for > or = 60% and > or = 80% stenosis, respectively, for comparison of 33 centers to the designated central reader. Comparison between the designated central reader and a second central reader derived percent agreements of 85.0% and 86.5% with kappa statistics of 0.69 and 0.41 for > or = 60% and > or = 80% stenoses, respectively, for arteries selected from the original group. Hence, agreement was slightly better between the enrolling centers and the designated central reader than between the two central readers. CONCLUSIONS: Both centralized and noncentralized (site-based) methods of angiographic measurement of stenosis are equally reliable for large, prospective, masked, multicenter trials when quality control measures are instituted to ensure uniform application of eligibility criteria.
Angiography↗
Antibodies against endothelial cells in patients with multiple sclerosis.
OBJECTIVES: The humoral immune response seems to play a role in the pathogenesis of multiple sclerosis (MS). The blood-brain-barrier (BBB) and particularly the endothelial cell may be a possible target for this immune response. MATERIAL & METHODS: using an ELISA technique, we have investigated the prevalence of antibodies directed against human vein endothelial cells in the sera of 84 patients with MS, 35 stroke patients, 50 systemic lupus erythematosus (SLE) and 76 normal controls. The measurements in MS patients were tested a second time after cytokine stimulation with gamma and beta-interferon at different doses. Seven MS patients (two positive and five negative) had three or more clinical assessments including the Expanded Disability Status Scale (EDSS) over a three-month period, and at least three AECA determinations were carried out. Gadolinium MRI examinations were performed monthly during these three months. RESULTS: Anti-endothelial cell antibodies (AECA) have been identified in 9 of 84 patients suffering from MS (10.71%), in 3 of 35 stroke patients (8.57%) and in 20 of 50 SLE patients (40%). None of 76 normal controls had a positive titre of AECA. Cytokine stimulations did not modify the detection of these antibodies. No correlation between AECA and different clinical parameters such as onset age, clinical symptoms at onset and at sampling, clinical course and score measured by the EDSS was found in MS patients. No relationship was found between MRI activity and the presence of AECA. CONCLUSION: AECA do not seem to be a marker for a specific subset of MS patients.
Adolescent↗
Inhibitory activity of the equine infectious anemia virus major 5' splice site in the absence of Rev.
The major 5' splice site of equine infectious anemia virus (EIAV) conforms to the consensus 5' splice site in eight consecutive positions and is located immediately upstream of the gag AUG. Our results show that the presence of this 5' splice site on the EIAV gag mRNA decreases Gag production 30- to 60-fold. This is caused by inefficient nuclear mRNA export and inefficient mRNA utilization. Inhibition could be overcome by providing human immunodeficiency virus type 1 Rev/Rev-responsive element, human T-cell leukemia virus type 1 Rex/Rex-responsive element, or simian retrovirus type 1 constitutive transport element. In addition, inhibition could be abolished by introducing single point mutations in the 5' splice site or by moving the 5' splice site away from its natural position immediately upstream of the gag AUG. This demonstrates that both maintenance of a perfect consensus 5' splice site and its proper location on the mRNA are important for inhibitory activity of the EIAV major 5' splice site.
Base Sequence↗
Identification of nuclear and cytoplasmic proteins that interact specifically with an AU-rich, cis-acting inhibitory sequence in the 3' untranslated region of human papillomavirus type 1 late mRNAs.
Expression of human papillomavirus late genes encoding L1 and L2 capsid proteins is restricted to terminally differentiated epithelial cells. We have previously identified and characterized an AU-rich, cis-acting negative regulatory element in the 3' untranslated region of human papillomavirus type 1 late mRNAs. This element acts posttranscriptionally to reduce mRNA levels and the translation efficiency of mRNAs. The experiments reported here are a continuation of our previous work. We have used RNA gel shifts and UV cross-linking assays to identify cellular proteins that interact with the inhibitory RNA sequence of human papillomavirus type 1. RNA gel shift assays established that cellular proteins interact with the AU-rich sequence. The binding of nuclear proteins was inhibited by competition with poly(U), whereas the binding of cytoplasmic proteins was inhibited by competition with poly(U) and also by competition with poly(A) and poly(G). Two nuclear proteins and two cytoplasmic proteins that bind specifically to the AU-rich RNA sequence were identified by UV cross-linking. These proteins did not bind to the 3' untranslated region of human papillomavirus type 1 early mRNAs, which does not show inhibitory activity. The cellular proteins identified in our experiments may therefore be involved in the inhibition of human papillomavirus type 1 late gene expression in nondifferentiated epithelial cells.
Base Sequence↗