Linkage results in schizophrenia.
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Genetic Linkage↗
Biomedical subjects
M Baron
Publications and source records attributed to M Baron.
Culture of the astaxanthinogenic yeast Phaffia rhodozyma in low-cost media.
Growth of the yeast Phaffia rhodozyma was carried out in a simplified medium based on less expensive nutrient sources, such as diluted sugar cane juice, urea, and sodium phosphate. The usual content of the astaxanthin, an oxygenated pink carotenoid useful for fish flesh staining, was improved along with with good cell yields (respective values of > 1300 micrograms/g cells and > 5 g cells/L were observed). Yeast invertase and urease must therefore play an important role in the implementation of low-cost culture media.
Carbon↗
Randomized, single-blinded trial of laparoscopic versus open appendectomy in children: effects on postoperative analgesia.
BACKGROUND: The benefit of laparoscopy to patients has been clearly established in adults undergoing cholecystectomy. Results are less clear for appendectomy. The current study was undertaken to compare the respective 3-day postoperative periods after laparoscopic and open appendectomy in children. METHODS: Sixty-three children (aged 8-15 yr) scheduled for appendectomy were randomly assigned to two groups: open and laparoscopic. Postoperative evaluation included delay of postoperative recovery (walking and feeding), pain assessment by visual analog scale during the 3 subsequent days, amount of nalbuphine administered via a patient-controlled analgesia system during the first 48 h and responses by children, parents, and nurses on the overall quality of analgesia. RESULTS: There was no difference between groups for demographic data (particularly macroscopic aspect of appendix) analgesia, sedation, delay before eating and walking, incidence of urinary retention, nausea, vomiting. Operative time was long (P < or = to 0.05) in the laparoscopic group (54 +/- 17 min) than in the open group (39 +/- 18 min). Thirty five percent of the children had pain at the shoulder in the LAP group versus ten percent in the open group (P < or = 0.05). CONCLUSIONS: Laparoscopy did not improve analgesia and postoperative recovery after appendectomy in children.
Adolescent↗
Escherichia coli thymidylate kinase: molecular cloning, nucleotide sequence, and genetic organization of the corresponding tmk locus.
Thymidylate kinase (dTMP kinase; EC 2.7.4.9) catalyzes the phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis. The nucleotide sequence of the tmk gene encoding this essential Escherichia coli enzyme is the last one among all the E. coli nucleoside and nucleotide kinase genes which has not yet been reported. By subcloning the 24.0-min region where the tmk gene has been previously mapped from the lambda phage 236 (E9G1) of the Kohara E. coli genomic library (Y. Kohara, K. Akiyama, and K. Isono, Cell 50:495-508, 1987), we precisely located tmk between acpP and holB genes. Here we report the nucleotide sequence of tmk, including the end portion of an upstream open reading frame (ORF 340) of unknown function that may be cotranscribed with the pabC gene. The tmk gene was located clockwise of and just upstream of the holB gene. Our sequencing data allowed the filling in of the unsequenced gap between the acpP and holB genes within the 24-min region of the E. coli chromosome. Identification of this region as the E. coli tmk gene was confirmed by functional complementation of a yeast dTMP kinase temperature-sensitive mutant and by in vitro enzyme assay of the thymidylate kinase activity in cell extracts of E. coli by use of tmk-overproducing plasmids. The deduced amino acid sequence of the E. coli tmk gene showed significant similarity to the sequences of the thymidylate kinases of vertebrates, yeasts, and viruses as well as two uncharacterized proteins of bacteria belonging to Bacillus and Haemophilus species.
Amino Acid Sequence↗
Effect of lymphocytes on hormonal secretion by autologous thyrocytes cultured in monolayers.
We studied the lymphocyte-induced alterations in hormonal metabolism and the production of tumour necrosis factor alpha (TNF-alpha) during coculture of thyrocytes and autologous lymphocytes from 20 patients with Graves' disease and from five normal subjects. Thyroglobulin (Tg) mRNA was assessed by slot-blot analysis under TSH stimulation. Tg, tri-iodothyronine (T3) and cAMP secretion in the presence of TSH were measured by RIA after 3 or 5 days of coculture. TNF-alpha levels produced after 5 days incubation were also assayed in lymphocyte culture and coculture media. Lymphocytes isolated from peripheral blood (PBLs) altered the production of Tg, T3 and cAMP in autologous thyrocytes. Intrathyroidal lymphocytes (ITLs) decreased Tg and cAMP secretion but had no effect on T3 secretion. The reductions in Tg and cAMP levels obtained with mechanically isolated ITLs (M-ITLs) were generally higher than those obtained with ITLs isolated by dispase (D-ITLs). No difference was seen between Graves' disease and normal cocultures. PBLs secreted large concentrations of TNF-alpha, larger than those obtained with M-ITLs whereas D-ITLs produced low amounts of this cytokine. In coculture, TNF-alpha levels were lower than those observed in lymphocyte culture. Significant correlations were obtained between TNF-alpha levels and the decrease in Tg, T3 and cAMP concentrations. The percentage of T lymphocytes was higher in PBLs and D-ITLs than in M-ITLs. B lymphocytes levels were higher in ITLs, especially M-ITLs, than in PBLs. TNF-alpha production by B lymphocytes was maximal in M-ITLs. In conclusion, lymphocytes induced a decrease in hormonal thyroid metabolism when cocultured with autologous thyrocytes. These perturbations may be attributed, at least partly, to TNF-alpha secreted by lymphocytes. TNF-alpha interacts via the adenylate cyclase pathway of TSH signal transduction.
Adult↗
Screening of Bothrops snake venoms for L-amino acid oxidase activity.
Toxins, enzymes, and biologically active peptides are the main components of snake venoms from the genus Bothrops. Following the venom inoculation, the local effects are hemorrhage, edema, and myonecrosis. Nineteen different species of Brazilian Bothrops were screened for protein content and L-amino acid oxidase activity. B. cotiara, formerly found in the South of Brazil, is now threatened with extinction. Its venom contains a highly hemorrhagic fraction and, as expected from the deep yellow color of the corresponding lyophilized powder, a high L-amino acid oxidase (LAO) activity was also characterized. Flavin adenine dinucleotide (FAD) is its associate coenzyme. B. cotiara venom LAO catalyzed the oxidative deamination of several L-amino acids, and the best substrates were methionine, leucine, tryptophan, and phenylalanine, hence, its potential application for the use of biosensors for aspartame determination and for the removal of amino acids from plasma. High levels for LAO were also found in other species than B. cotiara. In addition, the technique of isoelectric focusing (IEF) was employed as a powerful tool to study the iso- or multi-enzyme distribution for LAO activity in the B. cotiara snake venom.
Amino Acid Oxidoreductases↗
Frequency of positive family history in bipolar patients in a catchment-area population.
1. Major family studies of bipolar disorder report the frequency of affective disorder among probands' relatives, but do not usually report the frequency of a positive family history among probands. A single previous study was not population based. 2. The Division of Psychiatry of Ben Gurion University provides virtually all psychiatric services for a catchment area of 300,000 people. The authors reviewed the charts of all 236 treated bipolar I patients in 1991, and interviewed 177 of them with a modified FH-RDC. 3. 48% of probands had a family history of mental illness. 4. However, the present methods of ascertainment may have been insufficiently sensitive.
Bipolar Disorder↗
Medical treatment of postappendectomy intraperitoneal abscesses in children.
Treatment of postappendectomy intraperitoneal abscesses is classically surgical (drainage). We report a retrospective study (1988 to 1991) of our experience in providing exclusively medical treatment for 11 such isolated abscesses in children. The abscess was detected 7 times within the 10 days following appendectomy. Ultrasonography localized the abscess 7 times in the right iliac fossa and 4 times in Douglas' pouch. In 4 cases it was larger than 5 cm in diameter. Parenteral antibiotic therapy associated ticarcillin and clavulanic acid 6 times and piperacillin, tobramycin and metronidazole 5 times. Drug efficacy was evaluated by clinical signs (fever, pain, ileus) and ultrasonography. In one case, an associated ileus led to reoperation at day 4 of treatment. In the other 10 cases, clinical signs disappeared during the first week of treatment. At day 7, parenteral was replaced by oral antibiotic therapy (metronidazole 7 times, amoxicillin-clavulanic acid 3 times) continued until the abscess was no longer visualized on ultrasonography (5 times at 3 weeks, 5 times at 1 month). Medical treatment of isolated postappendectomy abscesses in children would thus appear to be a logical choice in the absence of an associated ileus.
Abdominal Abscess↗
Congenital heart disease in the adult patient: the value of plain film chest radiology.
Congenital heart disease (CHD) is a major clinical problem in children, occurring in 0.8% of newborns (1). In the past, most patients with CHD died in infancy. With improved surgical and postoperative care, as well as more accurate preoperative evaluation, the overall 10-year survival rate is > 90%. As a result, > 500,000 adults in the United States have surgically treated CHD (2). In addition, at least 150,000 adults are thought to have unrecognized, misdiagnosed, or recognized but untreated CHD (3,4). Diagnostic imaging procedures for the evaluation of CHD include plain film radiology, fluoroscopy, angiocardiography, echocardiography, scintigraphy, computed tomography (CT), and magnetic resonance imaging (MRI). Each has unique as well as overlapping abilities to characterize precisely cardiovascular anatomy and pathophysiology. We emphasize those congenital cardiac disorders found predominantly in adults. In addition, conditions that are usually unrecognized in childhood, "slip through the system", and become clinically recognized in adults for the first time, often with an atypical clinical presentation, are discussed (5). The interpreter of the plain film radiograph has a unique opportunity to identify and often characterize the severity of a congenital cardiac disorder that may be unrecognized by the patient's physician. Important clues found on plain film radiographs will suggest either additional studies to pin-point the type of CHD more precisely or that no additional studies are needed because the recognized lesion is incidental and not of clinical significance.
Adult↗
Searching for complex disease genes: can it be made any easier?
The search for complex disease genes is gaining momentum. Recent guidelines for expediting this effort, such as "intelligent" genome scanning and statistical criteria for detecting weak signals indicative of linkage, are discussed, with special reference to psychiatric disorders.
Base Composition↗
Genes and psychosis: old wine in new bottles?
Despite initial setbacks, linkage studies with DNA markers continue to occupy center stage in psychiatric research. Advances in molecular and statistical techniques have revived the search for disease genes, leading to a new harvest of findings. Most interest in recent years has focused on potential linkages between schizophrenia and chromosomes X-Y (the pseudoautosomal region) and 22q12-13.1, and between bipolar affective disorder and chromosomes 18 (pericentromeric region) and 21q22.3. This article provides a critical evaluation of theses studies, with implications for future research. Concerns over earlier linkage trials make this scrutiny current and topical.
Bipolar Disorder↗
Variability of skin scores and clinical measurements in scleroderma.
OBJECTIVE: To determine the variability of several clinical outcome measurements commonly used in scleroderma clinical trials. METHODS: Ten researchers, members of a multicenter placebo controlled trial of methotrexate in early diffuse scleroderma, studied the intraobserver and interobserver variability of variables used to assess efficacy in scleroderma trials. RESULTS: For most measures, the variability within an observer was less than that found between observers, and therefore the intraobserver reliability was better than the interobserver reliability. The reliability of the modified Rodnan skin score exceeded the Rodnan skin score. Measures with inherent interpretation such as global assessments and skin scores had more variability than easily performed measurements such as grip strength and oral opening. CONCLUSION: Some of our variability was higher than variability previously reported; this could be due to the large number of examiners and patients in our study.
Female↗
Compared results of random and HLA DR semi-identical transfusion protocols.
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Blood Transfusion↗
Further characterization of the NH2-terminal fibrin-binding site on fibronectin.
The fibronectin (Fn) monomer contains two major sites of fibrin binding affinity present within the NH2-terminal and COOH-terminal domains; they consist of five (1F1-5F1) and three (10F1-12F1) consecutive type 1 modules, respectively. Recently, we have reported that the fourth and fifth type 1 module pair (4F1.5F1) of the NH2-terminal domain of fibronectin demonstrated fibrin binding ability (Williams, M. J., Phan, I., Harvery, T. S., Rostagno, A., Gold, L. I., and Campbell, I. D. (1994) J. Mol. Biol. 235, 1303-1311). In an attempt to further localize fibrin binding activity and to characterize the nature of the interaction between different type 1 modules of Fn and fibrin, we have tested a range of recombinant proteins and subtilisin generated proteolytic fragments of Fn in an enzyme-linked immunosorbent assay (ELISA) and by fibrin affinity chromatography. Of the recombinant proteins, we found that only the 4F1.5F1 exhibited significant fibrin binding activity, while 1F1, 1F1.2F1, 7F1, and 10F1 had little to no affinity for fibrin. On a molar basis, 4-5 times more 4F1.5F1 than a proteolytic fragment, corresponding to 1F1-5F1 (25.9 kDa) was required to cause 50% inhibition (IC50) of intact biotinylated Fn binding to fibrin in a competitive ELISA. This suggests that all five type 1 modules in tandem engender higher fibrin binding activity than the 4F1.5F1 alone. Furthermore, since fibrin binding activity of the intact Fn molecule was inhibited, by 70-80%, by the 4F1.5F1, the 25.9-kDa fragment, and a MoAb mapped to an epitope on the 4F1.5F1, the fibrin-binding site within the 4F1.5F1 contributes greatly to the non-covalent interaction of intact Fn with fibrin. These results provide significant insight into the Fn/fibrin interaction, a major component of the processes of wound repair and fibrin matrix assembly.
Amino Acid Sequence↗
Genetic linkage and mental disorders: an update on analytic methodologies.
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Genetic Linkage↗
Novel strategies in molecular genetics of mental illness.
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Chromosome Mapping↗
Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial.
OBJECTIVE: To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine. METHODS: Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6-month prospective, double-blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo. RESULTS: After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6-month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1-month evaluation (odds ratio 3.3, 95% confidence interval 1.2-9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long-term response. CONCLUSION: Our data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long-term efficacy could not be demonstrated because of a higher-than-expected placebo response. Predictors of response to these drugs could not be determined.
Amitriptyline↗