Complete primary structure of the major component myoglobin of California gray whale (Eschrichtius gibbosus)

The complete primary structure of the major component myoglobin from the California gray whale, Eschrichtius gibbosus, was determined by specific cleavage of the protein to obtain large peptides for degradation by the automatic sequenator. Cleavage at the two methionine residues of the apomyoglobin with cyanogen bromide and at the three arginine residues of the methyl acetimidated protein with trypsin resulted in three and four easily separable peptides, respectively, which when sequenced accounted for 85% of the primary structure. The remainder of the covalent structure was obtained by further digestion of the central cyanogen bromide peptide with trypsin and S. aureus strain V8 protease. This protein differs from that of the sperm whale, Physeter catodon, at 12 positions, from that of the common porpoise, Phocoena phocoena, and the Black Sea dolphin, Delphinus delphis, at 14 positions, and from that of the Amazon River dolphin, Inia geoffrensis, at 7 positions. All substitutions observed in this sequence fit easily into the tertiary structure of sperm whale myoglobin.     

3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents

90K is a tumor-associated antigen. Using myelomonocytic cell line THP-1 we determined neopterin production and tryptophan degradation after exposure of cells to 90K in the presence and the absence of interferon-gamma. Interferon-gamma is a well known stimulus for THP-1 cells inducing e.g. neopterin production and tryptophan degradation. Treatment of cells with 50 micrograms/ml 90K induced significant neopterin formation, and the exposure of cells to 90K in addition to 100 U/ml interferon-gamma amplified neopterin production compared to the sole effect of interferon-gamma. In parallel, a significant degradation of tryptophan was observed in culture supernatants leading to the formation of kynurenine. When the cells were treated with the combination of 90K and interferon-gamma the degradation of tryptophan was further enhanced. The data demonstrate that tumor-associated antigen 90K interferes with immunocompetent target cells and is able to induce a biochemical response in monocytic cells.     

Large index-fingertip forces are produced by subject-independent patterns of muscle excitation

Are fingertip forces produced by subject-independent patterns of muscle excitation? If so, understanding the mechanical basis underlying these muscle coordination strategies would greatly assist surgeons in evaluating options for restoring grasping. With the finger in neutral ad- abduction and flexed 45 degrees at the MCP and PIP, and 10 degrees at DIP joints, eight subjects attempted to produce maximal voluntary forces in four orthogonal directions perpendicular to the distal phalanx (palmar, dorsal, lateral and medial) and in one direction collinear with it (distal). Forces were directed within 4.7 +/- 2.2 degrees (mean +/- S.D.) of target and their magnitudes clustered into three distinct levels (p < 0.05; post hoc pairwise RMANOVA). Palmar (27.9 +/- 4.1 N), distal (24.3 +/- 8.3 N) and medial (22.9 +/- 7.8 N) forces were highest, lateral (14.7 +/- 4.8 N) was intermediate, and dorsal (7.5 +/- 1.5 N) was lowest. Normalized fine-wire EMGs from all seven muscles revealed distinct muscle excitation groups for palmar, dorsal and distal forces (p < 0.05; post hoc pairwise RMANOVA). Palmar force used flexors, extensors and dorsal interosseous; dorsal force used all muscles; distal force used all muscles except for extensors; medial and lateral forces used all muscles including significant co-excitation of interossei. The excitation strategies predicted to achieve maximal force by a 3-D computer model (four pinjoints, inextensible tendons, extensor mechanism and isometric force models for all seven muscles) reproduced the observed use of extensors and absence of palmar interosseous to produce palmar force (to regulate net joint flexion torques), the absence of extensors for distal force, and the use of intrinsics (strong MCP flexors) for dorsal force. The model could not predict the interossei co-excitation seen for medial and lateral forces, which may be a strategy to prevent MCP joint damage. The model predicts distal force to be most sensitive to dorsal interosseous strength, and palmar and distal forces to be very sensitive to MCP and PIP flexor moment arms, and dorsal force to be sensitive to the moment arm of and the tension allocation to the PIP extensor tendon of the extensor mechanism.     

Posterior subcapsular cataracts, bruises and hoarseness in children with asthma receiving long-term treatment with inhaled budesonide

To study isoform-specific effects of apolipoprotein E (apoE) in vivo, we generated mice with a human APOE*2 allele in place of the mouse Apoe gene via targeted gene replacement in embryonic stem cells. Mice expressing human apoE2 (2/2) have virtually all the characteristics of type III hyperlipoproteinemia. Their plasma cholesterol and triglyceride levels are both twice to three times those in (normolipidemic) mice that are expressing human apoE3 (3/3) made in an identical manner. The 2/2 mice are markedly defective in clearing beta-migrating VLDL particles, and spontaneously develop atherosclerotic plaques, even on a regular diet. An atherogenic diet, high in fat and cholesterol, exacerbates development of atherosclerosis and xanthomas in the 2/2 mice. Thus, comparisons between the 2/2 and 3/3 mice unequivocally demonstrate that a single amino acid difference (Arg158 Cys) in the apoE protein is sufficient to cause type III HLP and spontaneous atherosclerosis in mice.     

Atrial natriuretic peptides in the heart and hemolymph of the oyster, Crassostrea virginica: a comparison with vertebrates

1. The content of atrial natriuretic peptides (ANPs) in the auricles of oysters, Crassostrea virginica, was significantly (P < 0.01) greater than in their ventricles. 2. High-performance gel permeation chromatography (HP-GPC) followed by ANF radioimmunoassay revealed two peaks in both oyster and vertebrate (rat) hearts--a major peak where the 12.6-14 kDa ANF prohormone elutes and a smaller peak where the pure human form of ANF elutes. 3. HP-GPC evaluation followed by proANF 31-67 radioimmunoassay revealed only an ANF-like prohormone while HP-GPC followed by proANF 1-30 radioimmunoassay revealed the ANF prohormone and a proANF 1-30-like peptide in oyster and rat hearts. 4. ANPs concentrations in hemolymph were 940 +/- 129, 225 +/- 25, and 100 +/- 10 pg/ml by the proANF 1-30, proANF 31-67, and ANF radioimmunoassays, respectively. 5. Atrial natriuretic-like peptides are present in the oyster heart in molecular species similar to vertebrate species and these peptides are also present in hemolymph.     

Assessment of cell death

The root-associated bacterium Azospirillum brasilense Sp7 produces the growth-stimulating phytohormone indole-3-acetic acid (= IAA) via the indole-3-pyruvate pathway. The DNA region containing ipdC, the structural gene for indole-3-pyruvate decarboxylase, was identified in a cosmid gene library of strain Sp7 by hybridization and has been sequenced. Upstream of the gene, two other ORF homologous to gltX and cysS were sequenced that are transcribed in the opposite direction. A functional analysis of the cloned ipdC region has been performed. To test the expression of the gene, a lacZ-Km cartridge was introduced into the gene. By this construct, tryptophan-dependent stimulation of gene expression in A. brasilense Sp7 was observed. Evidences for the existence of another copy of the ipdC gene in the Azospirillum genome are also reported.     

Safety and long-term durability of completion gastrectomy in 81 patients with postsurgical gastroparesis syndrome

Postsurgical gastroparesis syndrome (PGS) is characterized by postcibal nausea and vomiting and is associated with functional gastric dysmotility. Patients frequently present with marked weight loss and malnutrition requiring hospitalization and prolonged parenteral nutrition. Typically, these patients fail to respond to prokinetic agents. Gastric reoperations are frequent and usually unsuccessful. Near-completion gastrectomy (NCG) has proved useful in small series of patients, but long-term follow-up has been lacking. The purpose of this study is to assess the safety and durability of NCG in a large group of patients with PGS. Eighty-one patients with documented PGS who failed to respond to prokinetic drug therapy were treated with NCG over an 11-year period. NCG was standardized with a 55-cm Roux-en-Y reconstruction. Patients were evaluated by a retrospective chart review and a prospective phone interview that compared pre- and postoperative health status based on a standardized severity of symptoms score. There were no operative deaths or complications related to the anastomosis. Average patient follow-up was 56.1 months (range, 2-142 months). Fifteen patients died of unrelated causes, and 14 patients were lost to follow-up. The remaining 52 patients showed a significant overall decrease in severity of symptoms score largely due to reduction in gastrointestinal symptoms and to a smaller but significant reduction in systemic symptoms. Nearly 80 per cent of patients reported long-term relief of symptoms. NCG is the procedure of choice for carefully selected patients with documented. Low morbidity and durable results can be anticipated in the majority of patients.     

Unique sensing errors in third-generation implantable cardioverter-defibrillators

OBJECTIVES: Third-generation cardioverter-defibrillators appear to be susceptible to unique sensing errors. This study was performed to determine the incidence and types of sensing errors in combination therapy implantable devices. BACKGROUND: One of the advantages offered by third-generation implantable cardioverter-defibrillators is the combination of bradycardia and antitachycardia pacing and cardioversion-defibrillation capabilities in a single device. The potential for unique sensing errors, those caused by the conflicts presented by combining bradycardia and tachycardia sensing and therapy algorithms in the same device, has not been previously addressed. METHODS: To determine the incidence of important sensing errors, 61 patients with a combination therapy device (Cadence [Ventritex] and PCD [Medtronic]) were studied for a 25-month period. In addition to surface electrocardiographic recordings during implantation and routine device testing, real-time and stored electrograms recorded from the rate-sensing leads (Cadence) and real-time marker channel recordings (PCD) were reviewed to diagnose sensing errors that resulted in symptoms, device inefficacy or delivery of inappropriate therapy. After recognition, specific reprogramming steps were performed in an attempt to avoid recurrent sensing errors. RESULTS: A total of 13 sensing errors were diagnosed in 12 patients (19.7%); the incidence was similar in both devices. Five distinct categories of sensing errors were identified. After device reprogramming, only one recurrent error occurred in 98 patient-months of follow-up. CONCLUSIONS: Important sensing errors occur in approximately 20% of patients with third-generation combination therapy cardioverter-defibrillators. Prompt diagnosis of sensing errors can lead to specific reprogramming steps to avoid recurrent errors.     

A tannin anti-cancer promotor from Terminalia arjuna

A new ellagitannin named; arjunin, four known tannins and two phenolic acids were isolated from Terminalia arjuna. The structures were elucidated by spectroscopic analyses.