Showing papers by "Baylor College of Medicine published in 1990"
TL;DR: The Wnt-1 (int-1) proto-oncogene, which encodes a putative signaling molecule, is expressed exclusively in the developing central nervous system and adult testes and its normal role is in determination or subsequent development of a specific region of thecentral nervous system.
1,526 citations
TL;DR: The DATATOP database as discussed by the authors includes clinical information on 800 patients with early untreated Parkinson's disease (PD) and is well suited to explore clinical heterogeneity in PD patients, including Bradykinesia, and postural instability and gait difficulty (PIGD).
Abstract: The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.
1,164 citations
TL;DR: To facilitate the reading of this review, the various subtopics of this rapidly expanding field are presented, each of which is organized as a self-contained sub-chapter that can be read independently of the others.
1,081 citations
TL;DR: The concepts discussed in this review should provide not only a conceptual framework for further investigation of the pathophysiology of reversible ischemia-reperfusion injury but also a rationale for developing clinically applicable interventions designed to prevent postischemic ventricular dysfunction.
Abstract: Among the numerous mechanisms proposed for myocardial stunning, three appear to be more plausible: 1) generation of oxygen radicals, 2) calcium overload, and 3) excitation-contraction uncoupling First, the evidence for a pathogenetic role of oxygen-derived free radicals in myocardial stunning is overwhelming In the setting of a single 15-minute coronary occlusion, mitigation of stunning by antioxidants has been reproducibly observed by several independent laboratories Similar protection has been recently demonstrated in the conscious animal, that is, in the most physiological experimental preparation available Furthermore, generation of free radicals in the stunned myocardium has been directly demonstrated by spin trapping techniques, and attenuation of free radical generation has been repeatedly shown to result in attenuation of contractile dysfunction Numerous observations suggest that oxyradicals also contribute to stunning in other settings: after global ischemia in vitro, after global ischemia during cardioplegic arrest in vivo, and after multiple brief episodes of regional ischemia in vivo Compelling evidence indicates that the critical free radical damage occurs in the initial moments of reflow, so that myocardial stunning can be viewed as a sublethal form of oxyradical-mediated "reperfusion injury" Second, there is also considerable evidence that a transient calcium overload during early reperfusion contributes to postischemic dysfunction in vitro; however, the importance of this mechanism in vivo remains to be defined Third, inadequate release of calcium by the sarcoplasmic reticulum, with consequent excitation-contraction uncoupling, may occur after multiple brief episodes of regional ischemia, but its role in other forms of postischemic dysfunction has not been explored It is probable that multiple mechanisms contribute to the pathogenesis of myocardial stunning The three hypotheses outlined above are not mutually exclusive and in fact may represent different steps of the same pathophysiological cascade Thus, generation of oxyradicals may cause sarcoplasmic reticulum dysfunction, and both of these processes may lead to calcium overload, which in turn could exacerbate the damage initiated by oxygen species The concepts discussed in this review should provide not only a conceptual framework for further investigation of the pathophysiology of reversible ischemia-reperfusion injury but also a rationale for developing clinically applicable interventions designed to prevent postischemic ventricular dysfunction
969 citations
TL;DR: It is reported here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries.
Abstract: ATHEROSCLEROSIS in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators1–3—agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor)4. Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium5,6. Recently, 'cell-modified' or 'oxidized' low-density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties7. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators.
883 citations
TL;DR: There is a consensus that one major function is to inactivate receptor by blocking DNA binding, and posttranslational modifications such as phosphorylation have been postulated to modulate several functional properties of steroid receptors.
Abstract: Steroid receptors are a class of molecules that function as both signal transducers and transcription factors. From cloned sequences it is apparent that steroid receptors and other transcription factors belong to a superfamily of proteins that appear to function by similar mechanisms. Functional domains for hormone and DNA binding, and for transcriptional activation, have been defined for several receptors. In some cases, specific amino acids required for function have been identified. The multi-functional steroid receptor molecules are modular in nature in that domains function independently of structural position in receptor molecules and can even function after insertion into unrelated transactivation proteins. The mechanism of receptor action is complex and multistage and a number of unanswered questions remain to be defined. Receptors are inactive in the absence of hormone in vivo; the proposed components of this inactive complex include several proteins and RNA. Theories on the physiological role of HSP 90 in this complex range from an artifactual interaction to an absolute conformational requirement for hormone binding. Although its function has not been demonstrated clearly yet, there is a consensus that one major function is to inactivate receptor by blocking DNA binding. Most of the steroid receptors appear to be nuclear in the absence of hormone. The transformation process produces a receptor molecule that is capable of specific DNA binding and transcriptional activation. The specificity of DNA binding is conferred by as few as three amino acids in the first finger of the C1 region. Receptors appear to bind to DNA as dimers although whether dimers are preformed in cytoplasm remains unknown. Although the DNA binding domain is required for gene activation, other regions of the molecule in the carboxyl and amino terminus enhance activation function. Important interactions of steroid receptors with other receptors and unrelated transcription factors has been proposed and most certainly occurs. Finally, posttranslational modifications such as phosphorylation have been postulated to modulate several functional properties of steroid receptors.
816 citations
TL;DR: In this article, the role of neutrophils in the pathogenesis of hepatic ischemia/reperfusion injury was investigated in male Fischer rats, where the liver was subjected to 45 min of no-flow ischemia followed by reperfusion for up to 24 hours.
Abstract: To determine the role of neutrophils in the pathogenesis of hepatic ischemia/reperfusion injury, livers from male Fischer rats were subjected to 45 min of no-flow ischemia followed by reperfusion for up to 24 h Two phases of liver injury were identified, an initial phase during the first hour of reperfusion and a later progression phase with 80 +/- 3% hepatocyte necrosis and an 80-fold increase of neutrophil infiltration in the liver after 24 h Pretreatment with a monoclonal antibody against neutrophils, which caused consistent neutropenia, protected the liver from reperfusion injury as indicated by 28 +/- 10% necrosis, and 84% reduction of hepatic neutrophil accumulation and a complete recovery of the hepatic ATP content Our data suggest that the later progression phase of reperfusion injury after hepatic no-flow ischemia is mediated mainly by neutrophils
747 citations
737 citations
TL;DR: It is suggested that exons are recognized and defined as units during early assembly by binding of factors to the 3' end of the intron, followed by a search for a downstream 5' splice site.
Abstract: Interactions at the 3' end of the intron initiate spliceosome assembly and splice site selection in vertebrate pre-mRNAs. Multiple factors, including U1 small nuclear ribonucleoproteins (snRNPs), are involved in initial recognition at the 3' end of the intron. Experiments were designed to test the possibility that U1 snRNP interaction at the 3' end of the intron during early assembly functions to recognize and define the downstream exon and its resident 5' splice site. Splicing precursor RNAs constructed to have elongated second exons lacking 5' splice sites were deficient in spliceosome assembly and splicing activity in vitro. Similar substrates including a 5' splice site at the end of exon 2 assembled and spliced normally as long as the second exon was less than 300 nucleotides long. U2 snRNPs were required for protection of the 5' splice site terminating exon 2, suggesting direct communication during early assembly between factors binding the 3' and 5' splice sites bordering an exon. We suggest that exons are recognized and defined as units during early assembly by binding of factors to the 3' end of the intron, followed by a search for a downstream 5' splice site. In this view, only the presence of both a 3' and a 5' splice site in the correct orientation and within 300 nucleotides of one another will stable exon complexes be formed. Concerted recognition of exons may help explain the 300-nucleotide-length maximum of vertebrate internal exons, the mechanism whereby the splicing machinery ignores cryptic sites within introns, the mechanism whereby exon skipping is normally avoided, and the phenotypes of 5' splice site mutations that inhibit splicing of neighboring introns.
718 citations
TL;DR: HIV-1-infected human monocytoid cells, but not infected human lymphoid cells, released toxic agents that destroy chick and rat neurons in culture.
Abstract: Mononuclear phagocytes (microglia, macrophages, and macrophage-like giant cells) are the principal cellular targets for human immunodeficiency virus-1 (HIV-1) in the central nervous system (CNS). Since HIV-1 does not directly infect neurons, the causes for CNS dysfunction in acquired immunodeficiency syndrome (AIDS) remain uncertain. HIV-1-infected human monocytoid cells, but not infected human lymphoid cells, released toxic agents that destroy chick and rat neurons in culture. These neurotoxins were small, heat-stable, protease-resistant molecules that act by way of N-methyl-D-aspartate receptors. Macrophages and microglia infected with HIV-1 may produce neurologic disease through chronic secretion of neurotoxic factors.
643 citations
TL;DR: The availability of Norwalk-specific cDNA and the new sequence information of the viral genome should permit the development of sensitive diagnostic assays and studies of the molecular biology of the virus.
Abstract: Major epidemic outbreaks of acute gastroenteritis result from infections with Norwalk or Norwalk-like viruses. Virus purified from stool specimens of volunteers experimentally infected with Norwalk virus was used to construct recombinant complementary DNA (cDNA) and derive clones representing most of the viral genome. The specificity of the clones was shown by their hybridization with post- (but not pre-) infection stool samples from volunteers infected with Norwalk virus and with purified Norwalk virus. A correlation was observed between the appearance of hybridization signals in stool samples and clinical symptoms of acute gastroenteritis in volunteers. Hybridization assays between overlapping clones, restriction enzyme analyses, and partial nucleotide sequence information of the clones indicated that Norwalk virus contains a single-stranded RNA genome of positive sense, with a polyadenylated tail at the 3' end and a size of at least 7.5 kilobases. A consensus amino acid sequence motif typical of viral RNA-dependent RNA polymerases was identified in one of the Norwalk virus clones. The availability of Norwalk-specific cDNA and the new sequence information of the viral genome should permit the development of sensitive diagnostic assays and studies of the molecular biology of the virus.
Book•
05 Jul 1990TL;DR: This work has shown that Endothelium-Derived Relaxing Factor is a major factor in the regulation of neurohumoral regulation in humans and its applications in medicine and sport are still unclear.
Abstract: Introduction. Methods To Study Endothelium-Dependent Responses. Endothelium-Derived Relaxing Factor. Physiological Actions. Other Relaxing Substances Released By the Endothelium. Production of Contracting Agents. Local Regulation of Endothelium-Dependent Responses. Neurohumoral Regulation. Heterogeneity and Chronic Modulation. Disease. Therapeutic Implications. References. Subject Index.
TL;DR: Rapid-freezing electron microscopy was used to examine human red blood cells which were exposed to a radio-frequency electric field, and the distribution of pore sizes and pore dynamics suggests that interactions between the membrane and the submembrane cytoskeleton may have an important role in the formation and resealing of pores.
TL;DR: The structure of the liganded form of the phosphate-binding protein reveals the atomic features responsible for phosphate selectivity, either in monobasic or dibasic form, and the exclusion of sulphate, fundamental to understanding phosphate transport systems and molecular recognition of charged substrates or ions in other biological processes.
Abstract: TRANSPORT of the essential nutrient phosphorus—primarily in the form of orthophosphate—into cells and organelles is highly specific. This is exemplified by the uptake of phosphate or its close analogue arsenate by bacterial cells by way of a high affinity active transport system dependent on a phosphate-binding protein; this system is unable to recognize other inorganic oxyanions and is, moreover, distinct from the one for sulphate transport1,2. The phosphate-binding protein is a member of a family of periplasmic proteins acting as initial high-affinity receptors for the osmotic shock-sensitive active transport systems or permeases for various sugars, amino acids, oligopeptides, and oxyanions2,3. We report here the highly refined 1.7 A resolution X-ray structure of the liganded form of the phosphate-binding protein. The structure reveals the atomic features responsible for phosphate selectivity, either in monobasic or dibasic form, and the exclusion of sulphate. These features are fundamental to understanding phosphate transport systems and molecular recognition of charged substrates or ions in other biological processes.
TL;DR: Results indicate that two distinct classes of transcription factors can recognize common regulatory sequences, a phenomenon the authors refer to as cross-coupling.
TL;DR: This superfamily of regulatory molecules was shown to include also the receptors for thyroid hormone (T3) vitamin D3 and retinoic acid and perhaps more surprising was the inclusion of oncogenes such as v-erb A in this family.
Abstract: The overall molecular pathway for the action of steroid hormones has been known for the past 15 yr (1–9). Within the past 5 yr, the cDNAs for all major steroid hormones have been cloned and sequenced (10, 11). As might have been expected, they were related in structure and led to the definition of an even larger family of putative regulatory proteins. This superfamily of regulatory molecules was shown to include also the receptors for thyroid hormone (T3) vitamin D3 and retinoic acid. Perhaps more surprising was the inclusion of oncogenes such as v-erb A in this family. The latter is one of the two genes which comprise an oncogenic cassette in the avian myeloblastosis virus and appears to be a mutated form of a cellular gene coding for one of the multiple receptors for thyroid hormone. A summary of selected members of the steroid receptor superfamily is shown in Fig. 1.
TL;DR: The last five years have seen major advances in understanding of the central and generalized role of G-proteins as transducers of receptor signals into effector responses as outlined in Scheme 1.
Abstract: The last five years have seen major advances in our understanding of the central and generalized role of G-proteins as transducers of receptor signals into effector responses as outlined in Scheme 1. Signal-transducing G pro teins, in contrast to other GTP-binding proteins, are heterotrimers formed of one GTP-binding (and hydrolyzing) a subunit, one {3 subunit, and one 'Y subunit. I This increase in knowledge is perhaps best illustrated by the fact that
TL;DR: Regulation of tolbutamide-sensitive K+[ATP] current in neonatal rat ventricular myocytes is studied and it is found that alpha i1, alpha i2, and alpha i3 mimicked the effect of GTP gamma S, but not alpha o or Gs, suggesting that Gi alpha acts via a membrane-delimited pathway.
Abstract: ATP-sensitive K+ (K+[ATP]) current is thought to be regulated by GTP-binding proteins (G proteins), but the pathways that couple receptor, G protein, and channel have not been defined. We studied r...
Journal Article•
TL;DR: It is indicated that Mac-1 (CD11b/CD18) can mediate adhesion-dependent H2O2 production by human and canine neutrophils exposed to chemotactic factors.
Abstract: Human neutrophils exposed to protein-coated polystyrene or cultured endothelial monolayers produce large quantities of H2O2 in response to soluble stimuli that elicit little or no secretion of reactive oxygen species from cells in suspension. To characterize the mechanisms involved in this adherence-dependent respiratory burst, we have investigated the possible role of one integrin known to participate in the adhesion of neutrophils to endothelial cells, CD11b/CD18 (Mac-1). H2O2 production was examined with chemotactic factor-stimulated human and canine neutrophils exposed to protein-coated surfaces and cultured human and canine endothelial cells. The two protein-coated surfaces used were type I collagen-coated glass or plastic, a surface to which neither human nor canine neutrophils adhered, and keyhole limpet hemocyanin (KLH)-coated glass or plastic, a surface to which human and canine neutrophils adhered only after chemotactic stimulation. FMLP-stimulated human neutrophils and platelet activating factor-stimulated canine neutrophils failed to produce detectable H2O2 when in contact with type I collagen, but secreted large amounts of H2O2 when adherent to KLH or endothelial cell monolayers. FMLP-stimulated neutrophils from patients with CD18-deficiency failed to adhere to any of these surfaces and failed to produce H2O2 under these conditions. mAb reactive with CD18 and CD11b were equally effective in markedly inhibiting the adhesion of normal human neutrophils to these surfaces and markedly inhibited the production of H2O2. A mAb reactive with CD18 blocked adhesion of stimulated canine neutrophils, and mAb directed against both CD18 and CD11b blocked H2O2 production by canine neutrophils on KLH and endothelium. A nonbinding mAb and a mAb reactive with CD11a did not inhibit H2O2 production of human cells on KLH or endothelial monolayers, and nonbinding and binding control mAb did not inhibit H2O2 production by canine neutrophils. These results indicate that Mac-1 (CD11b/CD18) can mediate adhesion-dependent H2O2 production by human and canine neutrophils exposed to chemotactic factors.
TL;DR: CDNA clones encoding a major differentiation product of mouse epidermal cells are isolated and characterized, which has an amino acid composition similar to that of purified cell envelopes and is named loricrin on the basis of its presumed function.
TL;DR: This drug combination decreased the number of mononuclear phagocytes found within the gray matter of damaged spinal cord, improved the recovery of function of the hindlimbs and bladder, preserved spinal somatosensory evoked potentials, and promoted the survival of motor neurons.
Abstract: Transient ischemia to the lumbar and sacral sections of the spinal cord of rabbit leads to a deterioration in neurological function that usually worsens 24 to 48 hours after injury. This decline in movement of the hindlimbs develops simultaneously with the appearance of mononuclear phagocytes in the gray matter of injured neural tissue. Chloroquine and colchicine inhibit phagocytic and secretory functions in mononuclear phagocytes. When given up to 6 hours after an induced ischemic lesion in rabbit, this drug combination decreased the number of mononuclear phagocytes found within the gray matter of damaged spinal cord, improved the recovery of function of the hindlimbs and bladder, preserved spinal somatosensory evoked potentials, and promoted the survival of motor neurons. In contrast, the glucocorticoid dexamethasone, a weak inhibitor of mononuclear phagocytes in vivo, did not reduce the number of inflammatory cells in the spinal cord and did not improve motor and bladder functions. The suppression of mononuclear phagocytes soon after ischemic injury may offer a new approach in the treatment of vascular disease in the central nervous system.
TL;DR: Coronary patency rates associated with rt-PA are higher with early concomitant systemic heparin treatment than with concomant low-dose oral aspirin, and should be considered in the design and interpretation of clinical trials involving coronary thrombolytic therapy.
Abstract: Background. We report the results of the Heparin—Aspirin Reperfusion Trial, a collaborative study comparing early intravenous heparin with oral aspirin as adjunctive treatment when recombinant tissue plasminogen activator (rt-PA) is used for coronary thrombolysis during acute myocardial infarction. Methods. Two hundred five patients were randomly assigned to receive either immediate and then continuous intravenous heparin (starting with a 5000-unit bolus; n = 106) or immediate and then daily oral aspirin (80 mg; n = 99) together with rt-PA (100 mg intravenously over a six-hour period) initiated within six hours of the onset of symptoms. We evaluated the patency of the infarct-related artery by angiography 7 to 24 hours after beginning rt-PA infusion, the frequency of reocclusion of the artery by repeat angiography on day 7, and ischemic or hemorrhagic complications during the hospital stay. Results. At the time of the first angiogram, 82 percent of the infarct-related arteries in the patients ass...
TL;DR: It is now clear that G proteins also couple membrane receptors to ionic channels by a cytoplasmically independent, membrane-delimited path way, and it is likely that ionsic channels will join adenylyl cyclase and cGMP phosphodiesterase and possibly phospholiphase (PLC) and phospholipase A2 (PLA2) as direct targets for G proteins.
Abstract: In the most common forms of signaling, chemical messengers are used to transmit information from one cell to another and, in many cases, guanine nucleotide binding G proteins, coupling receptors to enzyme effectors, play a critical role in the response. Every response seems to include some change in the electrical properties of the cell and of the ionic channels from which these electrical properties are derived. Heretofore such changes were thought to be mediated by cytoplasmic pathways regulated by the G protein effector en zymes, but it is now clear that G proteins also couple membrane receptors to ionic channels by a cytoplasmically independent, membrane-delimited path way. These two pathways have the respective synonyms indirect and direct (Figure 1). Although a membrane intermediary has not yet been excluded, it is likely that ionic channels will join adenylyl cyclase (AC) and cGMP phosphodiesterase (cGMP PDE) and possibly phospholiphase (PLC) and phospholiphase A2 (PLA2) as direct targets for G proteins. Furthermore,
TL;DR: In this article, the effect of three growth factors on the actin and myosin gene families was investigated by Northern blot analysis in cultured neonatal rat cardiac myocytes, and three alpha-actin genes demonstrate distinct responses to acidic vs. basic FGF.
Abstract: Cardiac-specific gene expression is intricately regulated in response to developmental, hormonal, and hemodynamic stimuli. To test whether cardiac muscle might be a target for regulation by peptide growth factors, the effect of three growth factors on the actin and myosin gene families was investigated by Northern blot analysis in cultured neonatal rat cardiac myocytes. Transforming growth factor-beta 1 (TGF beta 1, 1 ng/ml) and basic fibroblast growth factor (FGF, 25 ng/ml) elicited changes corresponding to those induced by hemodynamic load. The "fetal" beta-myosin heavy chain (MHC) was up-regulated about four-fold, whereas the "adult" alpha MHC was inhibited greater than 50-60%; expression of alpha-skeletal actin increased approximately two-fold, with little or no change in alpha-cardiac actin. Thus, peptide growth factors alter the program of differentiated gene expression in cardiac myocytes, and are sufficient to provoke fetal contractile protein gene expression, characteristic of pressure-overload hypertrophy. Acidic FGF (25 ng/ml) produced seven- to eightfold reciprocal changes in MHC expression but, unlike either TGF-beta 1 or basic FGF, inhibited both striated alpha-actin genes by 70-90%. Expression of vascular smooth muscle alpha-actin, the earliest alpha-actin induced during cardiac myogenesis, was increased by all three growth factors. Thus, three alpha-actin genes demonstrate distinct responses to acidic vs. basic FGF.
TL;DR: It is concluded that plasma receptors have a constant relationship to tissue receptors, and their number in most instances reflects the rate of erythropoiesis.
TL;DR: The vagus provides an easily accessible, peripheral route to modulate CNS function and is likely to relate to effects on the reticular activating system.
Abstract: The vagus is a mixed nerve carrying somatic and visceral afferents and efferents. The majority of vagal nerve fibers are visceral afferents and have a wide distribution throughout the central nervous system (CNS) either monosynaptically or via the nucleus of the solitary tract. Besides activation of well-defined reflexes, vagal stimulation produces evoked potentials recorded from the cerebral cortex, the hippocampus, the thalamus, and the cerebellum. Activation of vagal afferents can depress monosynaptic reflexes, decrease the activity of spinothalamic neurons, and increase pain threshold. Depending on the stimulation parameters, vagal afferent stimulation in experimental animals can produce electroencephalographic (EEG) synchronization or desynchronization and has been shown to affect sleep states. The desychronization of the EEG appears to depend on activation of afferent fibers that have conduction velocities of less than or equal to 15 m/s. Vagal afferent stimulation can also influence the activity of interictal cortical spikes produced by topical strychnine application, and either attenuate or stop seizures produced by pentylenetetrazol, 3-mercaptoproprionic acid, maximal electroshock, and topical alumina gel. The mechanisms for the antiepileptic effects of vagal stimulation are not fully understood but probably relate to effects on the reticular activating system. The vagus provides an easily accessible, peripheral route to modulate CNS function.
TL;DR: Those who continued to work or retirees who elected to participate in regular activities sustained more constant CBF levels and scored better on cognitive testing after the fourth year of follow‐up compared to inactive retirees.
Abstract: Among neurologically normal volunteers approaching age 65 with an option for retirement, a four-year prospective longitudinal study was designed to examine effects of different levels of physical activity on cerebral perfusion by between-group comparisons. After the fourth year, cognitive performance was also tested. Three groups were compared, each composed of 30 elderly volunteers, assigned as follows: Group 1, who continued to work; Group 2, who retired but participated in regular physical activities; and Group 3, who retired but did not participate in regular, planned physical activities. Retirees who elected to become physically inactive exhibited significant declines in cerebral blood flow (CBF) throughout four years of follow-up. Those who continued to work or retirees who elected to participate in regular activities sustained more constant CBF levels. Active retirees and those who continued to work also scored better on cognitive testing after the fourth year of follow-up compared to inactive retirees.
TL;DR: The safety and preliminary efficacy of intravenous injections of Albunex were well tolerated and no serious side effects were noted in any of the patients, and the degree of ventricular cavity opacification appeared to be dose and concentration related.
TL;DR: The complete sequence of 57 kb of the human HPRT locus has been determined using automated fluorescent DNA sequencing using M13 (universal and reverse) and custom oligonucleotide primers.
TL;DR: This study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm.
Abstract: In the past five years, 477 patients with various focal dystonias and hemifacial spasm received 3,806 injections of botulinum A toxin for relief of involuntary spasms. A definite improvement with a global rating greater than or equal to 2 on a 0-4 scale, was obtained in all 13 patients with spasmodic dysphonia, 94% of 70 patients with blepharospasm, 92% of 13 patients with hemifacial spasm, 90% of 195 patients with cervical dystonia, 77% of 22 patients with hand dystonia, 73% of 45 patients with oromandibular dystonia, and in 90% of 21 patients with other focal dystonia who had adequate follow up. While the average duration of maximum improvement lasted about 11 weeks after an injection (range seven weeks in patients with hand dystonia to 15 weeks in patients with hemifacial spasm), some patients benefited for over a year. Only 16% of the 941 treatment visits with follow up were not successful. Except for transient focal weakness, there were very few complications or systemic effects attributed to the injections. This study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm.