Showing papers by "Icahn School of Medicine at Mount Sinai published in 1992"
Harvard University1, University of Texas Health Science Center at Houston2, Stony Brook University3, University of Manitoba4, Washington University in St. Louis5, University of Arizona6, University of Missouri7, Université de Montréal8, Icahn School of Medicine at Mount Sinai9, Laval University10, Yeshiva University11
TL;DR: In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events.
Abstract: Background. Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, long-term therapy with the angiotensin-converting—enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. Methods. Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive double-blind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. Results. Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent conf...
5,503 citations
2,145 citations
TL;DR: The evidence favoring the oxidant stress hypothesis is persuasive, but not yet fully established, and believes that this is the best hypothesis available at present.
Abstract: Oxidant stress, due to the formation of hydrogen peroxide and oxygen-derived free radicals, can cause cell damage due to chain reactions of membrane lipid peroxidation. Because the substantia nigra is rich in dopamine, which can undergo both enzymatic oxidation via monoamine oxidase and nonenzymatic autoxidation, hydrogen peroxide and oxyradicals (superoxide anion radical and hydroxyl radical) are generated in this midbrain nucleus. Although proof that oxidant stress actually causes the loss of monoaminergic neurons in patients with Parkinson's disease is lacking, there is a considerable body of evidence from studies in both animals and humans that support the concept. (1) Neurotoxins that selectively destroy the dopaminergic neurons in the nigra, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), appear to act via oxidant stress. (2) The substantia nigra of patients with Parkinson's disease reveals evidence of oxidant stress by the findings of increased lipid peroxidation and decreased reduced glutathione. (3) Total iron is increased and ferritin is reduced in the substantia nigra pars compacta in patients with Parkinson's disease. This combination suggests that this transition metal is in a low molecular weight form, capable of catalyzing nonenzymatic oxidative reactions, especially the conversion of hydrogen peroxide to hydroxyl radical, which is the most reactive of the oxygen radicals. (4) Neuromelanin, a product of dopamine autoxidation, can serve as a reservoir for iron, promoting the generation of oxyradicals. (5) Antioxidant defense mechanisms appear to be reduced in the parkinsonian substantia nigra with the findings of decreased activities of glutathione peroxidase and catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
956 citations
TL;DR: This work has compiled and aligned the 74 unique amino acid sequences published to date and review the present understanding of the structural motifs contributing to ligand binding and G-protein coupling.
Abstract: The multitude of G-protein coupled receptor (GPR) superfamily cDNAs recently isolated has exceeded the number of receptor subtypes anticipated by pharmacological studies. Analysis of the sequence similarities and unique features of the members of this family is valuable for designing strategies to isolate related cDNAs, for developing hypotheses concerning substrate-ligand and receptor-effector interactions, and for understanding the evolution of these genes. We have compiled and aligned the 74 unique amino acid sequences published to date and review the present understanding of the structural motifs contributing to ligand binding and G-protein coupling.
906 citations
TL;DR: Coronary-artery thrombi play an important part in the pathogenesis of unstable angina and acute myocardial infarction, however, the appearance of the thROMbi is different in the two conditions, possibly reflecting differences in the composition of age of theThrombi or the presence or absence of blood flow in the artery.
Abstract: Background. Disruption of an atherosclerotic plaque in a coronary artery followed by the formation of a thrombus is believed to be the cause of both unstable angina and acute myocardial infarction. Although thrombolytic therapy is efficacious in patients with acute myocardial infarction, for unknown reasons it is far less effective in patients with unstable angina. We postulated that there might be differences in the composition of the coronary-artery thrombi in unstable angina and acute myocardial infarction. Methods. To investigate the appearance of coronary-artery thrombi, we performed percutaneous transluminal coronary angioscopy in 15 patients with unstable angina and 16 with acute myocardial infarction. Angioscopy was performed within 48 hours after an episode of pain at rest in the patients with unstable angina and within 8 hours of onset in those with acute myocardial infarction. Results. Angioscopy revealed coronary thrombi in all but two patients (one in each group). Of the 29 patients ...
569 citations
TL;DR: FKBP12 and the RyRec are tightly associated in skeletal muscle SR on the basis of co-purification through sequential heparin-agarose, hydroxylapatite, and size exclusion chromatography columns and subcellular localization of both proteins to the terminal cisternae of the SR, and not in the longitudinal tubules of SR.
520 citations
TL;DR: It is concluded that the major lesion causing insulin resistance in PCO is a striking decrease in insulin sensitivity secondary to a defect in the insulin receptor and/or postreceptor signal transduction.
Abstract: Women with PCO have a unique but poorly characterized disorder of insulin action. Obese (n = 16) and nonobese (n = 14) PCO women and age- and weight-matched normal, nondiabetic ovulatory women (obese, n = 15; nonobese, n = 17) had insulin action determined in vivo with sequential multiple insulin dose euglycemic clamps and in isolated abdominal adipocytes to clarify the mechanisms of insulin resistance. PCO resulted in significant increases in the ED50 insulin for glucose utilization in vivo (P less than 0.001) and in adipocytes (P less than 0.01), without significant changes in adipocyte insulin-binding sites. PCO also resulted in significant decreases in maximal insulin-stimulated rates of glucose utilization in vivo (P less than 0.01) and in adipocytes (P less than 0.01). Obesity resulted in smaller decreases in insulin sensitivity than PCO (ED50 insulin, P less than 0.001 in vivo and P less than 0.05 in adipocytes), but greater decreases in insulin responsiveness (Vmax, P less than 0.001 in vivo and in adipocytes). The ED50 insulin for suppression of HGP was increased only in obese PCO women (P less than 0.001), and the interactions between PCO and obesity on this parameter were statistically significant. No significant correlations between androgen or estrogen levels and adipocyte insulin binding or action were found. Because insulin binding was not changed, we conclude that the major lesion causing insulin resistance in PCO is a striking decrease in insulin sensitivity secondary to a defect in the insulin receptor and/or postreceptor signal transduction. PCO also is associated with modest but significant decreases in glucose transport. These defects in insulin action appear to represent intrinsic abnormalities that are independent of obesity, metabolic derangements, body fat topography, and sex hormone levels. Conversely, changes in hepatic insulin sensitivity appear to be acquired with obesity.
520 citations
TL;DR: Impairment of delayed recall was again found to be the best discriminator for detecting mild cases of Alzheimer's disease and a combination of measures including fluency, praxis, and recognition memory best differentiated cases with mild dementia from those with either moderate or severe stages of disease.
Abstract: Our earlier studies using the Consortium to Establish a Registry of Alzheimer's Disease neuropsychological battery showed that delayed recall was a highly sensitive indicator of early Alzheimer's disease. None of the learning and memory measures in the battery were found to be useful in staging the severity of this form of dementia. This study explores the nonmemory functions (fluency, naming, and praxis) of the Consortium to Establish a Registry of Alzheimer's Disease battery and asks whether performance on any of these measures adds to the detection of early Alzheimer's disease or is sensitive to the later progression of the illness. We stratified patients with this disease according to severity (mild, moderate, severe), and compared them with age-, education-, and gender-matched control subjects (group N = 49 each). Multivariate procedures and cutting scores were used to determine the efficacy of the various measures in distinguishing between the cases and control subjects. Impairment of delayed recall was again found to be the best discriminator for detecting mild cases of Alzheimer's disease. Confrontation naming was the only nonmemory factor that assisted in this discrimination. For staging the illness, a combination of measures including fluency, praxis, and recognition memory best differentiated cases with mild dementia from those with either moderate or severe stages of disease. Measures of delayed recall quickly "bottomed out" in the patients with Alzheimer's disease and proved of little value in staging the disorder.(ABSTRACT TRUNCATED AT 250 WORDS)
494 citations
TL;DR: The association of aluminum and neurofibrillary tangle formation in Alzheimer's disease is confirmed and probe sites directed to neurons identified in snapfrozen cryostat sections revealed similar spectra with prominent aluminum‐related peaks, confirming that the findings are not related to exogenous contamination through fixation, embedding, or other procedures prior to analysis.
Abstract: We report the results of an examination of the elemental content of neurofibrillary tangle–bearing and neurofibrillary tangle–free neurons identified within the hippocampus of 10 subjects with Alzheimer's disease and 4 neuropathologically intact age-matched control subjects The study employed laser microprobe mass analysis (LAMMA), a technique that provides extremely sensitive multielement detection in plastic-embedded, semithin-sectioned tissues Evidence for the selective accumulation of aluminum within the neurofibrillary tangle–bearing neurons was obtained in all 10 subjects with Alzheimer's disease The site of aluminum deposition within these cells was the neurofibrillary tangle itself, and not the “nuclear region”, as we previously reported Iron accumulation was also detected within neurofibrillary tangles Evaluation for the accumulation of other elements within the tangle-bearing neurons failed to reveal any other metallic element as being consistently present In addition, probe sites directed to neurons identified in snapfrozen cryostat sections from 2 subjects with Alzheimer's disease revealed similar spectra with prominent aluminum-related peaks, confirming that our findings are not related to exogenous contamination through fixation, embedding, or other procedures prior to analysis This study further confirms the association of aluminum and neurofibrillary tangle formation in Alzheimer's disease
476 citations
TL;DR: The diversified and probably programmed binding functions of α2M indicate that in addition to its role in trapping proteinases, it has other biological activities that remain to be fully defined.
Abstract: Alpha 2-macroglobulin (alpha 2M) and related proteins share the function of binding host or foreign peptides and particles, thereby serving as humoral defense barriers against pathogens in the plasma and tissues of vertebrates. In human alpha 2M, several reactive sites including high-affinity sites for zinc, transglutaminase cross-linking sites, and reactive sites derived from the activated thiol ester can mediate reversible or irreversible capture of proteins of diverse biological functions. Alpha 2M interacts and captures virtually any proteinase whether self or foreign, suggesting a function as a unique "panproteinase inhibitor." Activation of alpha 2M generates novel binding sites, which mediate complex formation with cytokines and other peptides. Direct evidence of physical association of cytokines with activated alpha 2M indicated its role as biological response modifier in cell cultures. A mechanism commonly referred to as "clearance of activated alpha 2M" involves Ca(2+)-dependent binding to a specific cell surface receptor, a member of the low-density lipoprotein receptor supergene family, that mediates cellular uptake by endocytosis and delivery to endosomes and lysosomes. The peptide binding function of alpha 2M, therefore, may also be viewed as a mechanism that allows targeting of biologically active peptides to different cell types expressing the alpha 2M receptor. Internalized complexes may be dispatched into different pathways of endocytic/lysosomal pathways in a cell type-specific manner. In addition, bioactive peptides bound to alpha 2M may dissociate in the process of intracellular ligand sorting, thereby modulating cell function, or remain bound and share the catabolic fate of alpha 2M. The diversified and probably programmed binding functions of alpha 2M indicate that in addition to its role in trapping proteinases, it has other biological activities that remain to be fully defined. That alpha 2M may function as a binding and carrier protein with targeting characteristics is predicted from 1) the known functions of alpha 2M, and 2) the similarity of the fate of alpha 2M with proteins whose significance in targeting and intracellular trafficking has been studied in more detail.
468 citations
TL;DR: This work inserts into the germline of mice either a mutant or wild-type allele from a patient with retinitis pigmentosa and a missense mutation (P23H) in the rhodopsin gene, helping to establish the pathogenicity of mutant human P23H rod opsin and suggest that overexpression of wild- type human rods opsin leads to a remarkably similar photoreceptor degeneration.
TL;DR: The diagnostic criteria that are currently used with CT and MR imaging to diagnose metastases in cervical nodes are reviewed by evaluating nodal size, shape, grouping, and necrosis and extranodal tumor spread.
Abstract: Radiologists are frequently asked to evaluate cervical lymph nodes with CT or MR imaging to determine if metastases are present, how extensive the metastases are, and if they have spread from lymph nodes to critical adjacent structures such as the carotid artery and skull base. Accurate information of this type is essential if the most appropriate treatment is to be selected. The purpose of this report is to review the diagnostic criteria that are currently used with CT and MR imaging to diagnose metastases in cervical nodes by evaluating nodal size, shape, grouping, and necrosis and extranodal tumor spread. In addition, emphasis is placed on details that should be included in the CT and MR report, such as the location of the nodes, the presence of nodal calcification, and the presence of associated diseases such as parotid cysts that may suggest a specific diagnosis like HIV infection. Because optimal treatment planning depends on the combined information gleaned from the clinical evaluation and the imaging studies, it is essential that there be a close dialogue between clinicians and radiologists.
TL;DR: A diagnosis of neurocysticercosis should be considered in patients with seizures and radiologic evidence of cystic brain lesions, even in those who do not eat pork and who have not traveled to a country in which T. solium infection is endemic.
Abstract: Background and Methods. From June 1990 through July 1991, intracerebral infection with the larval stage of the pork tapeworm Taenia solium was diagnosed in four unrelated persons in an Orthodox Jewish community in New York City. None of the patients had eaten pork, and only one had traveled to a country in which T. solium infection was endemic. We investigated this outbreak, screened serum samples from family members and household contacts for antibodies to cysticercosis, and examined stool specimens from household employees for eggs of taenia species. Results. The four patients had recurrent seizures and brain lesions that were radiologically consistent with the presence of cysticerci. The diagnosis was confirmed in two patients by a brain biopsy, and in two by immunoblot assays for cysticercus antibodies. Of 17 immediate family members screened serologically, 7 from two families had cysticercus antibodies. Magnetic resonance imaging of the brain showed cystic lesions in two of the seropositive ...
TL;DR: The cloning of a cDNA representing the mouse GnRHR is reported and its identity is confirmed using Xenopus oocyte expression and it is reported that the nucleotide sequence encodes a 327-amino acid protein which has the seven putative transmembrane domains characteristic of G protein-coupled receptors, but which lacks a typical intracellular C-terminus.
Abstract: GnRH plays a pivotal role in the reproductive system, and GnRH analogs have wide therapeutic applications ranging from the treatment of prostatic cancer to infertility. Determination of the predicted structure of the GnRH receptor (GnRHR) would illuminate the mechanisms of receptor activation and regulation and allow directed design of improved GnRH analogs. We report the cloning of a cDNA representing the mouse GnRHR and confirm its identity using Xenopus oocyte expression. Injection of sense RNA transcript leads to the expression of a functional, high affinity GnRHR. Expression of the GnRHR using gonadotrope cell line RNA, however, is blocked by an antisense oligonucleotide. In situ hybridization in the rat anterior pituitary reveals a characteristic GnRHR distribution. The nucleotide sequence encodes a 327-amino acid protein which has the seven putative transmembrane domains characteristic of G protein-coupled receptors, but which lacks a typical intracellular C-terminus. The unusual structure and nove...
Journal Article•
TL;DR: The hypothesis that oxidative stress may be involved in the pathogenesis of Alzheimer's disease is supported.
Abstract: Membrane and cytoskeletal structures are known targets of oxidative injury. Brains from patients with Alzheimer's disease have cytoskeletal abnormalities and platelet and possible neuronal membrane lesions. The authors have recently demonstrated that superoxide anion is a powerful inducer of heat-shock protein synthesis, and have also shown that in response to oxidative stress or hyperthermia, intracellular levels of antioxidant enzymes increase to several folds. Whether the aforementioned mechanisms play a role in Alzheimer's disease has been suggested but is not totally established. While exploring this possibility, tissue sections from five brains with Alzheimer's disease and five neuropathologically normal age-matched controls were immunostained with polyclonal antibodies against superoxide dismutase (CuZn- and Mn- forms) and catalase. A standard avidin-biotin-peroxidase method was used for antigen detection. A subgroup of neurofibrillary tangles (15-25%) and senile plaques (50%) showed immunoreactivity for both enzymes with a staining pattern similar (but not identical) to that usually observed with antibodies against ubiquitin. Senile plaques displayed a granular pattern of immunostaining. Amyloid cores in mature classical plaques remained unstained. In addition, occasional elements with features consistent with reactive glial cells were strongly immunostained. Tangle-free neurons in both diseased and control brains showed weak to absent intracytoplasmic immunoreactivity. The immunoreactivity was totally abolished by preincubation of the primary antibodies with the corresponding purified antigens. These findings support the hypothesis that oxidative stress may be involved in the pathogenesis of Alzheimer's disease.
TL;DR: It is reported that the 113, 91, and 84 kd (ISGF3 alpha) proteins of ISGF3 contain conserved SH2 and SH3 domains, which indicate that a specific interferon alpha-induced cytoplasmic protein tyrosine kinase(s) can form a transient complex with ISGF2 alpha proteins.
TL;DR: The findings support the hypothesis of an enhanced sympathetic nervous system activation in PTSD, and suggest that increased sympathetic arousal may be closely linked to severity of certain PTSD symptom clusters.
Abstract: In the present study, we replicated and extended our previous findings of increased 24- hour urinary catecholamine excretion in posttraumatic stress disorder (PTSD). Dopamine, norepinephrine, and epinephrine concentrations were measured in 22 male patients with PTSD (14 inpatients and eight outpatie
TL;DR: This paper designate as a "nuon" any stretch of nucleic acid sequence that may be identifiable by any criterion and shows how such a general term will facilitate contemplation of the structural and functional contributions of such elements to the genome in its past, current, or future state.
Abstract: Genomic nomenclature has not kept pace with the levels and depth of analyzing and understanding genomic structure, function, and evolution. We wish to propose a general terminology that might aid the integrated study of evolution and molecular biology. Here we designate as a "nuon" any stretch of nucleic acid sequence that may be identifiable by any criterion. We show how such a general term will facilitate contemplation of the structural and functional contributions of such elements to the genome in its past, current, or future state. We focus in this paper on pseudogenes and dispersed repetitive elements, since their current names reflect the prevalent view that they constitute dispensable genomic noise (trash), rather than a vast repertoire of sequences with the capacity to shape an organism during evolution. This potential to contribute sequences for future use is reflected in the suggested terms "potonuons" or "potogenes." If such a potonuon has been coopted into a variant or novel function, an evolutionary process termed "exaptation," we employ the term "xaptonuon." If a potonuon remains without function (nonaptive nuon), it is a "nonaptation" and we term it "naptonuon." A number of examples for potonuons and xaptonuons are given.
TL;DR: The results of a meta-analysis examining studies which employed the construct of self-efficacy as a predictor of health related outcomes is presented.
Abstract: During the 1980's social cognitive theory has evolved as an explanation of human behavior. One of this theory's component constructs, self-efficacy, has received increasing attention as an antecedent to health related outcomes. The results of a meta-analysis examining studies which employed the construct of self-efficacy as a predictor of health related outcomes is presented. In the literature examined, subject ratings of self-efficacy were found to consistently predict subsequent health related outcomes.
TL;DR: Percutaneous injuries occur regularly during surgery, placing surgical personnel and, to a lesser extent, patients at risk for infection with blood-borne pathogens.
Abstract: Objective. —To study the numbers and circumstances of percutaneous injuries (eg, needle sticks, cuts) that occur during surgical procedures. Surgical personnel risk infection with blood-borne pathogens from percutaneous injuries; some injuries might also place patients at risk by exposing them to a health care worker's blood. Design. —Observers present at 1382 surgical procedures recorded information about the procedure, the personnel present, and percutaneous injuries that occurred. Setting. —Four US teaching hospitals during 1990. Participants. —Operating room personnel in five surgical specialties. Main Outcome Measures. —Numbers and circumstances of percutaneous injuries among surgical personnel and instances in which surgical instruments that had injured a worker recontacted the patient's surgical wound. Results. —Ninety-nine injuries occurred during 95 (6.9%) of the 1382 procedures. Seventy-six injuries (77%) were caused by suture needles and affected the nondominant hand (62 injuries [63%]), especially the distal forefinger. The risk of injury adjusted for confounding variables by logistic regression was higher during vaginal hysterectomy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.6 to 7.5) and lower during certain orthopedic procedures (OR, 0.2; CI, 0.1 to 0.7) than during 11 other types of procedures (reference group; OR, 1.0). Use of fingers rather than an instrument to hold the tissue being sutured was associated with 35 injuries (35%). Eighty-eight injuries (89%) were sustained by resident or attending surgeons; in 28 (32%) of the 88 injuries in surgeons, the sharp object that caused the injury recontacted the patient. Conclusion. —Percutaneous injuries occur regularly during surgery, placing surgical personnel and, to a lesser extent, patients at risk for infection with blood-borne pathogens. Many such injuries may be preventable with changes in devices, techniques, or protective equipment; all such measures require careful evaluation to determine their efficacy in reducing injury and their effect on patient care. ( JAMA . 1992;267:2899-2904)
TL;DR: The simplest kinetic model for inhibition is consistent with a mechanism involving a slow and reversible association of the enzyme with the inhibitor to form a EI complex.
Abstract: The multicatalytic proteinase complex (MPC), also referred to as proteasome, is a large molecular mass intracellular particle (approximately 700 kDa), which exhibits three distinct proteolytic activities designated as chymotrypsin-like, trypsin-like, and peptidylglutamyl-peptide hydrolyzing (PGPH), all sensitive to inhibition by 3,4-dichloroisocoumarin (DCI). The presence of a component resistant to inhibition by DCI with an apparent preference toward bonds on the carboxyl side of branched-chain amino acids has also been recently established. Peptide aldehydes and peptide alpha-keto esters containing a hydrophobic residue in the P1 position have been tested as potential inhibitors of the chymotrypsin-like activity. Three peptide aldehydes (benzyloxycarbonyl)-Leu-Leu-phenylalaninal (Z-LLF-CHO), N-acetyl-Leu-Leu-norleucinal (Ac-LLnL-CHO), and N-acetyl-Leu-Leu-methioninal (Ac-LLM-CHO) were found to be slow-binding reversible inhibitors with Ki values of 0.46, 5.7, and 33 microM, respectively. The simplest kinetic model for inhibition is consistent with a mechanism involving a slow and reversible association of the enzyme with the inhibitor to form a EI complex. The aldehyde inhibitors also inhibited the trypsin-like and PGPH activities of the complex albeit with much higher Ki values than those for chymotrypsin-like activity. Z-LLF-CHO, the most selective of the three aldehydes, did not inhibit the PGPH activity at concentrations of up to 200 microM and inhibited the trypsin-like activity with a Ki approximately 2 orders of magnitude higher than that for the chymotrypsin-like activity. The activity of the DCI-resistant component was not affected by Z-LLF-CHO.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Data suggest that expression of the genes encoding the cardiac DHP receptor and SR Ca(2+)-ATPase is reduced in the LV myocardium from patients with HF, contributing to LV systolic and diastolic dysfunction in patients with end-stage heart failure.
Abstract: Cytoplasmic free calcium ions (Ca2+) play a central role in excitation-contraction coupling of cardiac muscle. Abnormal Ca2+ handling has been implicated in systolic and diastolic dysfunction in patients with end-stage heart failure. The current study tests the hypothesis that expression of genes encoding proteins regulating myocardial Ca2+ homeostasis is altered in human heart failure. We analyzed RNA isolated from the left ventricular (LV) myocardium of 30 cardiac transplant recipients with end-stage heart failure (HF) and five organ donors (normal control), using cDNA probes specific for the cardiac dihydropyridine (DHP) receptor (the alpha 1 subunit of the DHP-sensitive Ca2+ channel) and cardiac calsequestrin of sarcoplasmic reticulum (SR). In addition, abundance of DHP binding sites was assessed by ligand binding techniques (n = 6 each for the patients and normal controls). There was no difference in the level of cardiac calsequestrin mRNA between the HF patients and normal controls. In contrast, the level of mRNA encoding the DHP receptor was decreased by 47% (P less than 0.001) in the LV myocardium from the patients with HF compared to the normal controls. The number of DHP binding sites was decreased by 35-48%. As reported previously, expression of the SR Ca(2+)-ATPase mRNA was also diminished by 50% (P less than 0.001) in the HF group. These data suggest that expression of the genes encoding the cardiac DHP receptor and SR Ca(2+)-ATPase is reduced in the LV myocardium from patients with HF. Altered expression of these genes may be related to abnormal Ca2+ handling in the failing myocardium, contributing to LV systolic and diastolic dysfunction in patients with end-stage heart failure.
TL;DR: In this paper, the dynein regulatory complex (drc) was found to be correlated with a deficiency of all four heavy chains of inner arms I2 and I3 from axonemes of suppressors pf2, pf3, suppf4, and suppf5.
Abstract: We provide indirect evidence that six axonemal proteins here referred to as "dynein regulatory complex" (drc) are located in close proximity with the inner dynein arms I2 and I3. Subsets of drc subunits are missing from five second-site suppressors, pf2, pf3, suppf3, suppf4, and suppf5, that restore flagellar motility but not radial spoke structure of radial spoke mutants. The absence of drc components is correlated with a deficiency of all four heavy chains of inner arms I2 and I3 from axonemes of suppressors pf2, pf3, suppf3, and suppf5. Similarly, inner arm subunits actin, p28, and caltractin/centrin, or subsets of them, are deficient in pf2, pf3, and suppf5. Recombinant strains carrying one of the mutations pf2, pf3, or suppf5 and the inner arm mutation ida4 are more defective for I2 inner arm heavy chains than the parent strains. This evidence indicates that at least one subunit of the drc affects the assembly of and interacts with the inner arms I2.
TL;DR: The association cortex of brains from dementia pugilistica patients demonstrated an inverse NFT distribution as compared to Alzheimer's disease, suggesting that a more circumscribed population of cortical pyramidal neurons might be affected in dementia pugs encephalopathy than in Alzhiemer's disease.
Abstract: Head trauma has been associated with the occurrence of Alzhiemer's disease and plays a clear role in the etiopathogenesis of the boxers encephalopathy referred to as dementia pugilistica. Neurofibrillary tangles (NFT), one of the pathological hallmarks of Alzheimer's disease are observed in very high densities in the brains of former professional boxers suffering from dementia pugilistica. In Alzheimer's disease, NFT display striking regional and laminar distribution patterns that have been correlated with the localization of neurons forming specific corticocortical connections. In dementia pugilistica cases, NFT were concentrated in the superficial layers in the neocortex, whereas in Alzheimer's disease they predominated in the deep layers. Thus, the association cortex of brains from dementia pugilistica patients demonstrated an inverse NFT distribution as compared to Alzheimer's disease. This finding suggests that a more circumscribed population of cortical pyramidal neurons might be affected in dementia pugilistica than in Alzheimer's disease.
TL;DR: A set of definitions and diagnostic criteria for the more common oral features of human immunodeficiency virus infection were prepared as the result of a consensus reached by a group of dental and medical clinicians, epidemiologists, and other experts as discussed by the authors.
Journal Article•
TL;DR: Appearance late in the course of ulcerative colitis, location proximal to the splenic flexure, and symptomatic large bowel obstruction distinguished the 17 malignant strictures from the 53 benign strictures in this series.
Abstract: Colorectal strictures, either benign or malignant, are not uncommon in ulcerative colitis. Fifty nine of 1156 ulcerative colitis patients (5%) admitted to this hospital between 1959 and 1983 developed 70 separate colorectal strictures. Seventeen of the 70 strictures (24%) proved to be malignant and the other 53 benign. Nine patients developed more than one stricture. Three principal features distinguished the 17 malignant from the 53 benign strictures in this series: (1) appearance late in the course of ulcerative colitis (61% probability of malignancy in strictures that develop after 20 years of disease v 0% probability in those occurring before 10 years); (2) location proximal to the splenic flexure (86% probability of malignancy v 47% in sigmoid, 10% in rectum, and 0% in splenic flexure and descending colon); and (3) symptomatic large bowel obstruction (100% probability of malignancy v only 14% in the absence of obstruction or constipation). Moreover, cancer associated with strictures tends to be more advanced (76% stage D, 24% A and B) than that which does not produce strictures (18% stage D, 59% A and B).
TL;DR: This is the first report indicating that the expression of the CRC mRNA is abnormal in end-stage human heart failure.(ABSTRACT TRUNCATED at 250 WORDS)
Abstract: The molecular basis for the systolic and diastolic dysfunction characteristic of end-stage heart failure in humans remains poorly understood. It has been proposed that both abnormal calcium handling and defects in the contractile apparatus may contribute to the myocardial dysfunction. Two channels, the calcium release channel (CRC) or ryanodine receptor of the sarcoplasmic reticulum (SR), and the slow calcium channel or dihydropyridine receptor (DHPR) of the transverse tubule, play key roles in regulating intracellular calcium concentration and in excitation-contraction (E-C) coupling in the heart. The DHPR serves as the voltage sensor and plasma membrane calcium channel resulting in activation of the CRC during E-C coupling in heart muscle. In this study, we investigated the levels of CRC expression in several forms of end-stage heart failure in humans. A cardiac CRC cDNA was cloned from rabbit and used as a probe for Northern blot analyses to determine mRNA levels in the left ventricles of normal (n = 4) and cardiomyopathic (n = 34) human hearts from patients undergoing cardiac transplantation. Compared with normal patients, patients with ischemic cardiomyopathy (n = 18) showed a 28% decrease in CRC mRNA levels (p less than 0.025) and patients with idiopathic dilated cardiomyopathy (n = 14) a nonsignificant 12% increase. In these same hearts, alpha-actin levels were unchanged in end-stage heart failure, as has been previously reported. This is the first report indicating that the expression of the CRC mRNA is abnormal in end-stage human heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: A major site of DNA bending is located 1.6 kb upstream of the P1 transcription start site of the human c-myc gene, near the center of a reported zone of initiation of DNA replication, and a repeated, purine-rich element at the bend site is specifically bound by a protein in HeLa cell nuclear extracts.
Abstract: A major site of DNA bending is located 1.6 kb upstream of the P1 transcription start site of the human c-myc gene, near the center of a reported zone of initiation of DNA replication. A repeated, purine-rich element, termed PUR, at the bend site is specifically bound by a protein in HeLa cell nuclear extracts. This protein has specific affinity for the purine-rich single strand of the element. Methylation interference maps a pattern of specific contact points with guanosine bases in a 24-mer oligonucleotide containing the element. UV cross-linking reveals that contact is made by a polypeptide of approximately 28 kDa. The PUR element is present at origins of replication and in gene flanking regions in a variety of eukaryotes from yeasts through humans. The consensus sequence GGNNGAGGGAGARRRR has been derived. This element is present near centers of regions of two mammalian loci (human c-myc and hamster dhfr) recently reported as initiation zones for DNA replication. A 24-mer oligonucleotide representing the hamster dhfr version of the PUR element effectively competes with the human c-myc version for binding to Pur.