Characterization of an influenza A virus from seals

An influenza A virus antigenically similar to A/FPV/Dutch/27 (Hav1Neq1) [H7N7] was isolated from harbor seals (Phoca vitulina) that had died of acute hemorrhagic pneumonia on Cape Cod Peninsula, beginning in the winter of 1979–1980. High titers of virus were obtained from the lungs and lower titers from the brains of the seals. Although antigenic analyses and characterization of the RNAs show that all of the genes and gene products are closely related to different avian influenza viruses, biologically the virus behaves more like a mammalian strain. The seal virus replicated and produced pneumonia in experimentally infected harbor seals, but the clinical course and pathology were less severe than in the natural infection; the virus also replicated in ferrets, cats, and pigs but produced no disease. In avian species, the seal influenza virus replicated poorly, produced no disease signs, and was not shed in the feces. Although the seal influenza virus can cause conjunctivitis in humans who have known contamination of the eyes from infected animals, serological studies detected no evidence of seroconversion among persons working with infected seals or with the virus. Preliminary studies detected antibodies to this virus in harbor seals on the New England coast but not in harbor seals, gray seals, or fur seals from other areas, suggesting that this virus may be a new introduction to this species. An Hav1Neq1 [H7N7] virus was also isolated from feral ducks in Iceland in 1980, but the two viruses could be distinguished by analysis of their RNAs and host range. The A/Seal/Mass/1/80 influenza virus provides the first evidence suggesting that a strain deriving all of its genes from one or more avian influenza viruses can be associated with severe disease in a mammalian population in nature. Whether this breach of species specificity represents a unique event in influenza evolution remains to be determined, but raises the possibility that human or animal influenza viruses may be derived directly from avian strains.     

Long-term mortality in patients with type 2 diabetes undergoing coronary angiography: the impact of glucose-lowering treatment

Aims/hypothesis  

The aim of this study was to analyse whether the increased mortality rates observed in insulin-treated patients with type 2 diabetes and coronary artery disease are explained by comorbidities and complications.     

Minisatellite mapping in manic depression

Hypervariable regions of DNA exist at many discrete loci in the human genome. Variations in the length of specific classes of hypervariable DNA termed “minisatellite” sequences may be detected by hybridisation of radioactive probes composed of a common10–15 base pair repeat or “core” sequence which is shared by each of the minisatellite loci. Such a procedure was used to perform linkage analysis on a kindred in which a disease allele causing manic depression appeared to be segregating as an autosomal dominant. Results indicate no apparent linkage between a manic depression allele and at least 20 hypervariable genetic loci which acted as markers. However, because of the hypervariability of the minisatellite loci these results do not preclude similar analyses of other manic depressive pedigrees being productive because each such family will have distinct observable minisatellite alleles at loci specific to that family. The method could be usefully applied to the genetic analysis of other psychiatric disorders where heterogeneity is suspected and where a single autosomal major gene locus appears to be responsible for causing multiple cases within a single kindred.     

Effect of varying drop size on the efficacy and safety of a topical beta blocker

We studied the effects on efficacy and safety of varying the drop size of a topical solution of levobunolol 0.5%. In a double-masked, crossover acute study, we administered a single drop of either 35 microL of vehicle, or 20, 35, or 50 microL of levobunolol one hour before the subjects began a ten-minute treadmill challenge electrocardiogram. After exercise the mean heart rate was 111 beats per minute (bpm) in the vehicle group and 102 to 103 bpm in the three levobunolol groups, which were significantly different from the control group but not from each other. In a randomized double-masked, parallel, chronic study, 117 patients with elevated intraocular pressure (IOP) instilled one of the three drop sizes of levobunolol twice daily for three months. Mean decreases in IOP ranged from 5.1 to 6.0 mmHg in the three groups, not significantly different from each other in mean IOP, heart rate, or blood pressure. We conclude that drop size in the range tested had no clinically significant effect on either efficacy or safety of a beta blocker such as levobunolol.     

Support for involvement of the AHI1 locus in schizophrenia

Recently, markers in the Abelson Helper Integration Site 1 (AHI1) region were shown to be associated with schizophrenia in a family sample of Israeli-Arabs. Here, we report a study evaluating the relevance of the AHI1 region to schizophrenia in an Icelandic sample. Seven markers shown to confer risk in the previous report were typed in 608 patients diagnosed with broad schizophrenia and 1,504 controls. Odds ratios for the overtransmitted alleles in the Israeli-Arab families ranged from 1.15 to 1.29 in the Icelandic sample. After Bonferroni correction for the seven markers tested, two markers were significantly associated with schizophrenia. Thus, our results are in general agreement with the previous report, with the strongest association signal observed in a region upstream of the AHI1 gene.     

Megakaryocytopoiesis and granulopoiesis in W/Wv mice: comparisons between bone marrow and spleen

To determine how megakaryocyte progenitor cells (CFU-M) of W/Wv mice are affected by the hematopoietic stem cell abnormality, megakaryocytopoiesis was studied in the spleen and marrow of these genetically anemic W/Wv mice. CFU-M were assayed in the soft gel colony-forming system. Megakaryocyte colony size was determined by counting the number of megakaryocytes per colony, and megakaryocyte diameter was determined on acetylcholinesterase-stained cytocentrifuged cell preparations with use of an eyepiece micrometer. In spite of normal blood platelet levels, megakaryocyte level was reduced in the spleen and humerus to about 60% that of +/+ littermates. Megakaryocyte diameters were increased in W/Wv mice. CFU-M in W/Wv mice were reduced to 40% the number seen in the spleen of +/+ mice and to 62% in the humerus. In cell cycle studies, significantly fewer marrow CFU-M were in DNA synthesis in W/Wv mice compared with +/+ animals, but similar numbers of cells were in cycle in the spleen for both genotypes. No difference was observed between W/Wv and +/+ CFU-M in their requirement for exogenous colony-stimulating activity or in the distribution of colony sizes. However, CFU-M-derived colonies cloned from adherent cell-depleted marrow cells were significantly smaller compared with those cultured from unfractionated marrow cells. Results for granulocytes and granulocyte-macrophage progenitor cells (CFU-GM) were similar to those obtained for the megakaryocyte series, indicating that the abnormalities are present in different cell lineages. These results suggest that the macromegakaryocytosis of W/Wv mice appears to be a compensation for the megakaryocytopenia. Cells in the progenitor cell compartment appeared not to be involved in this compensation. Furthermore, adherent cells appear to elaborate a factor regulating megakaryocyte development. These findings are compatible with two-level regulation of megakaryocyte formation and a complex mechanism of blood platelet level regulation.     

Linkage between tyrosine hydroxylase gene and affective disorder cannot be excluded in two of six pedigrees

Genetic linkage between manic depression and DNA markers on the short arm of chromosome 11 was first reported in 1987 but not supported by further analyses. However, genetic markers at the tyrosine hydroxylase (TH) gene located within this region have been reported to show allelic association with the affective disorder phenotype. We present the results of a linkage analysis using polymorphic DNA segments within the TH gene and the nearby dopamine D4 receptor (DRD4) gene in 6 families multiply affected with affective disorder. Small positive Lod scores were obtained in 2 of 6 pedigrees with the TH polymorphism which may be indicative of genetic heterogeneity. © 1993 Wiley-Liss, Inc.     

Monoamine metabolism during chronic benzodiazepine treatment and withdrawal

Long-term normal-dose benzodiazepine treatment in seven patients was associated with reduced urinary excretion of MOPEG (4-hydroxy-3-methoxy-phenylglycol). Following the discontinuation of the drugs a characteristic withdrawal reaction occurred, with an increase towards normal values of the MOPEG excretion levels and changes in the excretion of 5-HIAA (5-hydroxyindoleacetic acid). No significant changes in the 24-hr urinary excretion of free cortisol or HMMA (3-methoxy-hydroxy-mandelic acid) were detected.     

Topical timolol and epinephrine: biochemical actions and interactions in the rabbit eye in vivo

The effects of topical 0.5% timolol maleate and 1% or 2% levo-epinephrine hydrochloride on aqueous humor cyclic-AMP and intraocular pressure were assessed in 97 normotensive New Zealand white rabbits in vivo. The study was conducted using three experimental protocols: (A) timolol and epinephrine individually, (B) timolol and epinephrine in coadministration, and (C) timolol and epinephrine in crossover, applied either in a single dose, twice a day for two days, and/or twice a day for six days. These studies demonstrated that timolol has complex biochemical actions, one of which is beta-adrenergic antagonism. By itself, timolol had no effect on cyclic-AMP levels. However, when used in both single-dose coadministration and in pretreatment in six-day crossover with epinephrine, it significantly diminished the cyclic-AMP elevation produced by a single dose of epinephrine. In the six-day crossover protocol, pretreatment with timolol also significantly reduced the ocular hypotensive effect of a single dose of epinephrine, thereby correlating biochemical cause with clinical effect. Yet, timolol alone had no ocular hypotensive effect. Therefore, timolol's biochemical actions in this animal model cannot explain its marked clinical efficacy in man, which appears to depend on more complex pharmacologic actions.     

Withdrawal from long-term benzodiazepine treatment

Long-term, normal-dose benzodiazepine treatment was discontinued in 16 patients who were suspected of being dependent on their medication. The withdrawal was gradual, placebo-controlled, and double-blind. All the patients experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to prewithdrawal levels over the next two to four weeks. Other features of the withdrawal included disturbance of sleep and appetite and noticeable weight loss. Electroencephalography showed appreciable reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was recorded by the Digit Symbol Substitution Test. Because of the risk of dependence on benzodiazepines these agents should probably not be given as regular daily treatment for chronic anxiety.