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Biomedical subjects

A Rosen

Publications and source records attributed to A Rosen.

At least 127 records · Page 7Linked to original sources
PubMed1997

Stress fracture of the ulna in a female table tennis tournament player.

A stress fracture of the diaphyseal ulna occurred in a 19-year-old female competitive table tennis player with a history of secondary amenorrhea. Stress fractures are one of more common problems occurring in vigorous sports. Stress fractures of the ulna can result from any repeated forearm flexor muscle activity. In our case stress was caused by increased athletic activity by additional training twice a day six times a week starting eighth weeks before first signs of pain and by rhythmic repeated submaximal work load in a new job additional to training. Physical training is often associated with menstrual irregularity. Hormonal factors were known for six months. Spontaneous onset of pain in women and previous history of amenorrhea should include stress fractures as differential diagnosis.

Adult↗
PubMed1997

Anatomical basis for nerve injury during laparoscopic hernia repair.

One of the most distressing complications of laparoscopic hernia repair is injury to the lateral cutaneous nerve of the thigh. The relation of this nerve to the laparoscopic technique of hernia repair was studied in 50 adult groins. Recommendations for avoidance of injury are delineated based on the anatomical findings.

Adult↗
PubMed1996

Sequential activation of three distinct ICE-like activities in Fas-ligated Jurkat cells.

ICE family proteases have been implicated as important effectors of the apoptotic pathway, perhaps acting hierarchically in a protease cascade. Using cleavage of endogenous protease substrates as probes, three distinct tiers of ICE-like activity were observed after Fas ligation in Jurkat cells. The earliest cleavage detected (30 min) was of fodrin, and produced a 150 kDa fragment. The second phase of cleavage (50 min) involved PARP, U1-70kDa and DNA-PKcs, all substrates of the CPP32-like proteases. Lamin B cleavage was observed during the third cleavage phase (90 min). Distinct inhibition profiles obtained using a panel of peptide-based inhibitors of ICE-like proteases clearly distinguished the three different cleavage phases. These studies provide evidence for a sequence of ICE-like proteolytic activity during apoptosis. The early fodrin cleavage, producing a 150 kDa fragment, identifies an ICE-like activity proximal to CPP32 in Fas-induced Jurkat cell apoptosis.

Antibodies, Monoclonal↗
PubMed1996

Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death.

Proteolysis mediated by the interleukin 1 beta-converting enzyme (ICE) homologues is an important mechanism of the apoptotic process. The ICE homologue apopain/CPP-32/Yama (subsequently referred to as apopain) cleaves poly(ADP-ribose)polymerase (PARP) early during apoptosis. Additional apoptosis-specific protein cleavages have been observed in which the direct involvement of ICE-like proteases has been postulated. These substrates include the 70-kD protein component of the U1-ribonucleoprotein (U1-70kD), and the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). The present studies demonstrate that U1-70kD and DNA-PKcs are excellent substrates for apopain, with cleavage occurring at sites that are highly similar to the cleavage site within PARP. The fragments generated from isolated protein substrates by apopain are identical to those observed in intact apoptotic cells, in apoptotic cell extracts, and in normal cell extracts to which apopain has been added. Like PARP, cleavage of these substrates in apoptotic cell extracts is abolished by nanomolar concentrations of Ac-DEVD-CHO and micromolar amounts of Ac-YVAD-CHO, confirming the involvement of apopain or an apopain-like activity. We propose that a central function of apopain or similar homologues in apoptosis is the cleavage of nuclear repair proteins, thereby abolishing their critical homeostatic functions.

Amino Acid Sequence↗
PubMed1996

Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: implications for coagulation events and antigenic spread in systemic lupus erythematosus.

The restriction of phosphatidylserine (PtdSer) to the inner surface of the plasma membrane bilayer is lost early during apoptosis. Since PtdSer is a potent surface procoagulant, and since there is an increased incidence of coagulation events in patients with systemic lupus erythematosus (SLE) who have anti-phospholipid antibodies, we addressed whether apoptotic cells are procoagulant and whether anti-phospholipid antibodies influence this. Apoptotic HeLa cells, human endothelial cells, and a murine pre-B-cell line were markedly procoagulant in a modified Russell viper venom assay. This procoagulant effect was entirely abolished by addition of the PtdSer-binding protein, annexin V, confirming that it was PtdSer-dependent. The procoagulant effect was also abolished by addition of IgG purified from the plasma of three patients with anti-phospholipid antibody syndrome, but not IgG from normal controls. Confocal microscopy of apoptotic cells stained with fluorescein-isothiocyanate-conjugated-annexin V demonstrated (Ca2+)-dependent binding to the surface of membrane blebs o apoptotic cells, but not to intracellular membranes. Recent data indicate that the surface blebs of apoptotic cells constitute an important immunogenic particle in SLE. We propose that the PtdSer exposed on the outside of these blebs can induce the production of anti-phospholipid antibodies, which might also enhance the immunogenicity of the bleb contents. When apoptosis occurs in a microenvironment in direct contact with circulating plasma, the unique procoagulant consequences of the apoptotic surface may additionally be expressed. This might explain the increased incidence of pathological intravascular coagulation events that occur in some lupus patients who have anti-phospholipid antibodies.

Animals↗
PubMed1996

Development of a rapid means of estimating the haemoglobin F content of candidate fetal cells isolated from maternal blood using HPLC.

Prenatal diagnosis of genetic disorders in nucleated fetal red blood cells present in maternal blood requires methods to detect and enrich for such cells. Here we describe a rapid high performance liquid chromatography (HPLC) method that allows one to determine as few as 100 cells containing haemoglobin F (HbF) in the presence of a vast excess of haemoglobin A (HbA)-producing cells. The HPLC separations of haemoglobins were performed with a weak cation exchange column-silica gel-bound asparaginic acid-and ammonium phosphate buffer as the mobile phase. Separations were carried out in 7 min. When applied to estimation of the recovery of fetal cells from maternal blood, the HPLC method indicates in a timely manner whether or not to proceed with further techniques (i.e., FISH or PCR). Several current techniques such as Ficoll gradients and fluorescence (FACS) or magnetic (MACS) activated cell sorting were thus evaluated. Unexpectedly, our method indicates high cell losses with both single gradient and triple density Ficoll pre-enrichment methods. Less than 20 per cent of the nucleated red blood cells can be recovered in the most optimal setting. Lysis of erythrocytes may be an alternative technique that leaves nucleated red blood cells of all maturation stages intact. Thus, any further improvements in the technology for fetal cell recovery may be aided by monitoring the yield with HPLC.

Cell Separation↗
PubMed1996

NOD mouse diabetes: the ubiquitous mouse hsp60 is a beta-cell target antigen of autoimmune T cells.

In the NOD mouse, the onset of beta-cell destruction is associated with spontaneous development of T-lymphocytes reactive to members of the 60 kDa heat shock protein (hsp60) family, including the Mycobacterial (MT) and the human (H) hsp60 molecules. Diabetes in the NOD mouse is a spontaneous tissue-specific autoimmune disease occurring without prior immunization. Therefore, it has been suggested that the anti-hsp60 T cells involved in the autoimmune diabetes of NOD mice might reflect molecular mimicry between MT-hsp60 and a beta-cell tissue specific molecule sharing similar T cell epitopes, the p277 peptide of hsp60 in particular. We cloned and expressed the mouse hsp60 cDNA from a beta-cell tumour. This mouse beta-cell hsp60 cDNA was found to be identical in sequence to the hsp60 of mouse fibroblasts. We further report that NOD spleen cells and an NOD diabetogenic T cell clone C9 responded to the recombinant mouse hsp60 and to its peptide M-p277 to the same extent as to H-hsp60 and H-p277. Splenocytes of mice of other strains did not respond to p277. Moreover, treatment of 3 month old NOD mice with the non-modified self M-p277 peptide was as efficient as H-p277, from which it differs in one amino acid, in halting progression of the disease. Thus, anti-H-p277 T cells modulating diabetes in the NOD mouse are autoreactive, and are targeted at the mouse beta-cell hsp60, which is not tissue specific. These findings raise the question of how a non-tissue specific molecule may be a target of a tissue-specific autoimmune disease.

Amino Acid Sequence↗
PubMed1996

Methodology of serial ECG classification using an adaptation of the NOVACODE for Q wave myocardial infarction in the Bypass Angioplasty Revascularization Investigation (BARI).

Serial electrocardiographic (ECG) changes are a critical component of the diagnostic algorithm for classification of myocardial ischemic events in large-scale clinical trials. This study describes a computerized serial ECG classification program developed at the St. Louis University Core ECG Laboratory for use in the Bypass Angioplasty Revascularization Investigation (BARI) trial, in which patients with multivessel coronary artery disease were randomized to receive either coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. The St. Louis University program detects and codes serial changes in Q, ST, and T wave items according to Minnesota code (MC) criteria using a modified NOVACODE hierarchical classification system. Measurements using a seven-power calibrated coding loupe are used to generate the MC from a customized software program. Significant minor or major changes are detected by the serial comparison program and referred to a physician coder for verification. Serial comparison coding rules are used to adjust for weaknesses in the standard MC classification system resulting from instability at decision boundaries. Of 4,244 BARI randomized and registry study participants with follow-up ECGs received at the Core ECG Laboratory as of March 1995, a grade 2 MC Q wave progression was noted in 568 participants (13.4%) using MC criteria alone, as compared with 367 (8.6%) after the St. Louis University coding rules were applied. The incidence of grade 1 MC Q wave progressions was 16.4% (697/4,244) versus 6.1% (259/4,244) when the St. Louis University program was applied. Intraobserver variability for grade 2 Q wave progression codes determined from a sample of 812 serial.

Algorithms↗
PubMed1996

Microtubule-active agents mimic lipopolysaccharides in priming macrophages for enhanced arachidonic acid metabolism.

Macrophages play a crucial role in inflammation and host defense, in part, by secreting metabolites of arachidonic acid (20:4). Bacterial lipopolysaccharides (LPS) are poor agonists of the 20:4 cascade, but do have the capacity to prime macrophages for greatly increased 20:4 metabolism upon subsequent stimulation with activators of protein kinase C (PKC). The microtubule-stabilizing agent, taxol, mimics many of the effects of LPS in macrophages. We demonstrate in this study that taxol, like LPS, primes murine peritoneal macrophages for an enhanced release of 20:4 in response to both phorbol 12-myristate 13-acetate (PMA) and zymosan. Taxol and LPS, when used at maximum concentrations, acted additively to prime macrophages for PMA-stimulated release of 20:4, suggesting that the two agents signal through different pathways. Interestingly, agents that stimulate the depolymerization of microtubules, colchicine and nocodazole, also primed macrophages for an enhanced release of 20:4 in response to PMA, however, they did not prime when zymosan was the stimulus. We conclude that agents that disrupt the microtubule network prime resident peritoneal macrophages for enhanced release of 20:4.

Animals↗
PubMed1996

Nutritional, socioeconomic, and reproductive factors in relation to female breast cancer mortality: findings from a cross-national study.

Using data from 66 countries, we conducted an international comparison study to identify the most important predictors of female breast cancer mortality rates. This study was unique in that it included data on per capita tobacco disappearance, alcohol consumption, socioeconomic status (SES), reproductive factors, and a wide array of nutritional data. Results of correlation and single independent-variable linear regression models indicated that breast cancer mortality was most strongly associated with dietary factors typically associated with affluence, especially animal products. The strongest negative (i.e., protective) associations were with those variables related to increased fertility and population growth. A multiple linear regression that accounted for all important predictors simultaneously explained 91% of the variability in mortality rates across these countries. This model indicated a strong positive association between breast cancer mortality and calories from animal sources. Fish and cereal products as well as annual percentage growth in population appeared to exert protective effects. Despite the limitations of this type of analysis, the observed effect of high meat and animal product consumption, the major contributor to variability in dietary fat, as well as the protective effect of increased fertility are consistent with the known biology of breast cancer. The protective effect of fish and cereal consumption that we observed will require further study.

Aged↗
PubMed1996

In vivo-in vitro correlations with a commercial dissolution simulator. Studies on the H2 receptor antagonist mifentidine.

The dissolution profile of mifentidine (CAS 83184-43-4), which is used as an antagonist of histamine at H2 receptors, was determined using a dissolution simulator. The use of an absorption simulator, which is designed to provide an estimate of the optimum sampling scheme for the dissolution simulator, provides useful data for this purpose. Various in vivo-in vitro correlations for mifentidine were examined and were found to be good.

Absorption↗
PubMed1995

DNA-dependent protein kinase is one of a subset of autoantigens specifically cleaved early during apoptosis.

Proteolytic cleavage of key substrates appears to be an important biochemical mechanism underlying the apoptotic process, and the centrality of interleukin 1 beta-converting enzyme (ICE)-like proteases as mediators of apoptosis has been suggested. The identification of the relevant substrates of the ICE protease family during apoptosis therefore constitutes a major challenge. Using human autoantibodies, we demonstrate here that a subset of autoantigens is specifically cleaved early during apoptosis. One of these cleaved molecules is identified as the catalytic subunit of the DNA-dependent protein kinase. The time courses of all proteolytic cleavages are identical and coincide with the onset of morphologic apoptosis. Furthermore, all cleavages share the same inhibition characteristics, which implicate an ICE-like activity(ies). We propose that cleavage of these autoantigens targets these molecules for an autoimmune response by revealing immunocryptic fragments in a proimmune apoptotic setting. Study of the immunogenicity of these fragments may yield insights into the autoimmune targeting of molecules. Moreover, the autoantibodies described will be valuable tools for the elucidation of mechanistically important proteolytic steps along the apoptotic pathway.

Amino Acid Sequence↗
PubMed1995

Homeopathy, other forms of alternative medicine sources of ongoing debate among physicians, patients.

Amy Rosen is the 1994 winner of the Amy Chouinard Memorial Essay Contest. Named in memory of longtime CMAJ and Canadian Journal of Surgery contributor Amy Chouinard, the competition is intended to stimulate interest in medical and health-related writing among journalism students. The winning essay examines the growing public interest in homeopathic medicine and physicians' opinions of the trend.

Attitude↗
PubMed1995

Novel packages of viral and self-antigens are generated during apoptosis.

Immune context is an essential determinant of the host response to potential autoantigens. The clustering of the autoantigens targeted in systemic lupus erythematosus within surface blebs of apoptotic cells generates high concentrations of autoantigen within discrete subcellular packages. We demonstrate here that when apoptosis is induced by Sindbis virus infection, viral antigens and autoantigens cocluster exclusively in small surface blebs of apoptotic cells. The surface of these blebs is rich in viral glycoproteins, and virions can be seen blebbing from their surface. We propose that these blebs of mixed foreign and self-origin define a novel immune context that may challenge self-tolerance.

Antigens, Viral↗
PubMed1995

DNA amplification of HER-2/neu and INT-2 oncogenes in epithelial ovarian cancer.

OBJECTIVE: Oncogene alterations are thought to be prognostic indices in patients with breast cancer. The present study was carried out to investigate the amplification of the HER-2/neu and INT-2 oncogenes in ovarian cancer. METHODS: In a retrospective study of 196 patients with epithelial ovarian cancer, the amplification of the oncogenes HER-2/neu and INT-2 in the DNA of paraffin-embedded tumor cells was determined by quantitative PCR. The purpose of this study was to analyze whether the two oncogenes correlated with such predictive factors as FIGO stage, histological grade, ascites, postoperative residual tumor mass, hormone receptor content, and preoperative CA 125 serum levels. The effect of HER-2/neu and INT-2 amplification on patient survival was also studied. RESULTS: The only correlation found in this study was between INT-2 and preoperative CA 125 levels (P = 0.03). No correlations were demonstrable between HER-2/neu (log-rank test; P = 0.67) and INT-2 (log-rank test; P = 0.75) amplifications and overall survival. CONCLUSION: Unlike the established prognostic factors, neither HER-2/neu nor INT-2 appears to be predictive for survival in patients with ovarian cancer.

Adolescent↗