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Biomedical subjects

J M Polo

Publications and source records attributed to J M Polo.

At least 37 records · Page 2Linked to original sources

Staphylinid (rove) beetle dermatitis outbreak in the American southwest?

An outbreak of a blistering disease was reported in a military unit training in the Arizona desert during heavy rain and flooding. In a unit of 249 personnel, 33 presented with dermatologic complaints, and 4 met stringent diagnostic criteria for dermatitis linearis. A fifth patient presented with symptoms and signs of "Nairobi eye." Staphylinid (rove) beetles related to the paederids, which have been responsible for vesicular dermatitis outbreaks in other parts of the world but not previously in the United States, were collected at the site. Reports in the antique scientific literature document paederids in the area after periodic floods. These findings suggest that rove beetle dermatitis should be added to the differential diagnosis of vesicular dermatitis in western North America.

Animals↗

DNA immunization against herpes simplex virus: enhanced efficacy using a Sindbis virus-based vector.

Previously we reported the development of a plasmid DNA expression vector system derived from Sindbis virus (T. W. Dubensky, Jr., et al., J. Virol. 70:508-519, 1996). In vitro, such vectors exhibit high-level heterologous gene expression via self-amplifying cytoplasmic RNA replication. In the present study, we demonstrated the in vivo efficacy of the Sindbis virus-based pSIN vectors as DNA vaccines. A single intramuscular immunization of BALB/c mice with pSIN vectors expressing the glycoprotein B of herpes simplex virus type 1 induced a broad spectrum of immune responses, including virus-specific antibodies, cytotoxic T cells, and protection from lethal virus challenge in two different murine models. In addition, dosing studies demonstrated that the pSIN vectors were superior to a conventional plasmid DNA vector in the induction of all immune parameters tested. In general, 100- to 1,000-fold-lower doses of pSIN were needed to induce the same level of responsiveness as that achieved with the conventional plasmid DNA vector. In some instances, significant immune responses were induced with a single dose of pSIN as low as 10 ng/mouse. These results indicate the potential usefulness of alphavirus-based vectors for DNA immunization in general and more specifically as a herpes simplex virus vaccine.

Animals↗

[Miller-Fisher syndrome: electrophysiological serial study of five patients].

OBJECTIVE: The object of the present study is to show the spectrum of neurophysiological findings during clinical course of Miller Fisher syndrome (MFS), avoiding the controversy over a combined central and peripheral pathology. PATIENTS AND METHODS: We report five patients with a syndrome of ophthalmoplegia, ataxia and areflexia. A similar episode had been suffered previously by 2 of these patients, 14 and 13 years before. In one of them the second episode evolved to a typical Guillain-Barré syndrome (GBS). Motor and sensory conduction velocity of upper and lower limbs, F waves, blink-reflex and somatosensory evoked potentials were recorded in all cases. Needle electromyography in four and brainstem evoked potentials in three of them and the jaw-reflex in another one. RESULTS: In all patients there was a markedly reduced amplitude of the distal sensory evoked response, and no signs of denervation in the EMG. The other results were variable both interindividually and intraindividually. The severity of abnormalities was also different between different patients. The clinical recovery was always accompanied by a improvement of neurophysiological parameters. CONCLUSIONS: The electrophysiological findings in MFS can be variable but they appear always related with the clinical symptomatology. We report for the first time a case in whom the jaw-reflex was abnormal whereas the blink-reflex was normal.

Adult↗

Validity of a velodrome test for competitive road cyclists.

The aim of this study was to evaluate the validity of a velodrome field test consisting of repeated rides of 2,280 m, with an initial speed of 28 km.h-1 and increments of 1.5 km.h-1 interspersed with 1-min recovery periods until exhaustion. A group of 12 male competitive road cyclists performed maximal cycling tests under velodrome and laboratory conditions. Velodrome oxygen uptake (VO2) and power output were estimated using equations previously published. Physiological responses to the two tests were compared. Relationships between performance in the velodrome and physiological parameters measured in the laboratory were studied. Maximal power output, heart rate and VO2 were similar in the velodrome and the laboratory [372 (SD 50) vs 365 (SD 36) W, 195 (SD 8) vs 196 (SD 9) beats.min-1 and 4.49 (SD 0.56) vs 4.49 (SD 0.46) l.min-1, respectively], while maximal velodrome blood lactate concentration was significantly higher [13.5 (SD 2.1) vs 11.8 (SD 3.1) mmol.l-1]. Velodrome heart rate was higher at submaximal exercise intensities representing 40%, 50% and 60% of maximal aerobic power, and velodrome blood lactate concentration was also higher at 60%, 70% and 80% of maximal aerobic power. The laboratory parameter that showed the highest correlation with the maximal cycling speed in the velodrome was maximal oxygen uptake (VO2max) expressed per unit of body mass (r = 0.93). In addition, the accuracy of different methods of estimation of the metabolic cost of cycling, rolling resistance, air resistance coefficients and VO2max were compared. Significant differences were found. In conclusion, the present results indicated the validity of a velodrome test used to estimate maximal aerobic parameters of competitive road cyclists, as long as the estimation is made using established equations. When road cyclists are tested in the laboratory, physiological values should be expressed per unit of body surface area or body mass, to predict more accurately the cyclist's performance level under specific field conditions.

Adult↗

Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene transfer.

Several DNA-based Sindbis virus vectors were constructed to investigate the feasibility and potential applications for initiating the virus life cycle in cells transfected directly with plasmid DNA. These vectors, when transfected into mammalian cells, have been used to produce virus, to express heterologous genes, and to produce infectious vector particles. This approach involved the conversion of a self-replicating vector RNA (replicon) into a layered DNA-based expression system. The first layer includes a eukaryotic RNA polymerase II expression cassette that initiates nuclear transcription of an RNA which corresponds to the Sindbis virus vector replicon. Following transport of this RNA from the nucleus to the cytoplasm, the second layer, autocatalytic amplification of the vector, proceeds according to the Sindbis virus replication cycle and results in expression of the heterologous gene. The Sindbis virus DNA vectors expressed reporter genes in transfected cells at levels that were comparable to those of in vitro-transcribed RNA replicons and were approximately 10-fold higher than the levels produced by conventional RNA polymerase II-dependent plasmids in which the promoter and reporter gene were linked directly. Reporter gene expression was also observed in rodent muscle following injection with Sindbis virus DNA vectors. In a second application, packaged vector particles were produced in cells cotransfected with complementing replicon and defective helper DNAs. The Sindbis virus-derived DNA vectors described here increase the utility of alphavirus-based vector systems in general and also provide a vector with broad potential applications for genetic immunization.

Animals↗

Deduced consensus sequence of Sindbis virus strain AR339: mutations contained in laboratory strains which affect cell culture and in vivo phenotypes.

The consensus sequence of the Sindbis virus AR339 isolate, the prototype alphavirus, has been deduced. THe results presented here suggest (i) that a substantial proportion of the sequence divergence evident between the consensus sequence and sequences of laboratory strains of AR339 has resulted from selection for efficient growth in cell culture, (ii) that many of these changes affect the virulence of the virus in animal models, and (iii) that such modified genetic backgrounds present in laboratory strains can exert a significant influence on genetic studies of virus pathogenesis and host range. A laboratory strain of Sindbis virus AR339 was sequenced and cloned as a cDNA (pTRSB) from which infectious virus (TRSB) could be derived. The consensus sequence was deduced from the complete sequences of pTRSB and HRsp (E. G. Strauss, C. M. Rice, and J. H. Strauss, Virology 133:92-110, 1984), from partial sequences of the glycoprotein genes of three other AR339 laboratory strains, and by comparison with the sequences of the glycoprotein genes of three other AR339 sequence. HRsp differed form the consensus sequence by eight coding changes, and TRSB differed by three coding changes. In the 5' untranslated region, HRsp differed from the consensus sequence at nucleotide (nt) 5. These differences were likely the result of cell culture passage of the original AR339 isolate. At three of the difference loci (one in TRSB and two in HRsp), selection of cell-culture-adaptive mutations was documented with Sindbis virus or other alphaviruses. Selection in cell culture often results in attenuation of virulence in animals. Considering the TRSB and HRsp sequences together, one noncoding difference from the consensus (an A-for-G substitution in the 5' untranslated region at nt 5) and six coding differences in the glycoprotein genes (at E2 amino acids 1, 3, 70, and 172 and at E1 amino acids 72 and 237) were at loci which, either individually or in combination, significantly affected alphavirus virulence in mice. Although the levels of virulence of isogenic strains containing either nt 5 A or nt 5 G did not differ significantly in neonatal mice, the presence of nt 5 A greatly enhanced the effect of a second attenuating mutation in the E2 gene. These results suggest that minimal differences in the "wild type" genetic background into which an additional mutation is introduced can have a dramatic effect on apparent virulence and pathogenesis phenotypes. A cDNA clone of the consensus AR339 sequence, a sequence devoid of occult attenuating mutations introduced by cell culture passage, will allow the molecular genetic examination of cell culture and in vivo phenotypes of a virus which may best reflect the sequence of Sindbis virus AR339 at the time of its isolation.

Alphavirus Infections↗

[Distribution of headache by diagnosis as the reason for neurologic consultation].

BACKGROUND: The aim of this study was to analyze the diagnostic distribution of patients consulting because of headache in a neurology department. METHODS: The clinical records of 3,498 patients who had consulted specifically due to headache between 1978 to 1993 were retrospectively studied. Diagnosis was reclassified according to the criteria of the new headache classification with data concerning the age of onset and sex distribution also being collected. RESULTS: The most frequent diagnoses were migraine (1,802 patients; 52%) tension-type headache (113; 32%), followed in decreasing order by trigeminal neuralgia, post injury headache, cluster headache, subarachnoid hemorrhage, analgesic-ergotamine abuse headache, tumoral headache, cervical disease headache, benign exertional headache, due to paranasal sinusal disorders and benign intracranial hypertension. Female predominance was observed in the whole series (68%) as in the groups with migraine, tension-type headache, neuralgia headache by analgesic-ergotamine drugs and benign intracranial hypertension. Cluster, post injury, tumor and provoked headaches (cough, exertional and sexual) were found to be more frequent in men. The age of onset was very specific for each kind of headache. The percentage of symptomatic headaches increased in direct relation to age, being 10 fold higher in patients over the age of 65. CONCLUSIONS: The diagnostic distribution of headache as a cause of medical consultation is very different to the prevalence of different headaches. This distribution by diagnosis largely depends on the age of the patient at the time of headaches onset [corrected].

Adolescent↗

Transgenic mice support replication of hepatitis delta virus RNA in multiple tissues, particularly in skeletal muscle.

Hepatitis delta virus (HDV) is hepatotropic and frequently causes fulminant hepatitis in both human and nonhuman primate hosts. To understand the molecular basis of HDV tissue tropism and the mechanism of pathogenesis, transgenic mice in which replication-competent HDV dimeric RNA is expressed under the control of either liver-specific or universal transcriptional promoters were developed. The expressed RNA replicated efficiently in the liver and several tissues of nonhepatic origin. Surprisingly, maximal replication of HDV RNA occurred in skeletal muscle and was almost 100-fold greater than in the liver. These findings suggest that the hepatotropism of HDV is most likely a receptor-mediated restriction and that muscle-specific factors may facilitate HDV RNA replication. No evidence of cytopathology was apparent in most of the tissues examined, including the liver, supporting the contention that hepatocellular disease is not mediated by direct cytopathological effects associated with HDV RNA replication and gene expression. However, mild muscle atrophy in some of the transgenic mice was noted. Delta antigen was detected in the nuclei of myocytes. Only the small form, not the large form, of delta antigen was detected, suggesting that the RNA editing event which causes the conversion of delta antigen did not occur in transgenic mice. Furthermore, the 0.8-kb antigenomic RNA species, which is postulated to be the mRNA for delta antigen, was not detected in mice. The preferential replication of HDV RNA in skeletal muscle suggests that HDV RNA replication can be facilitated by certain muscle-specific factors.

Actins↗

Replication of hepatitis delta virus RNA in mice after intramuscular injection of plasmid DNA.

To establish a readily manipulable small-animal system for the study of human hepatitis delta virus (HDV) replication in vivo, plasmid DNAs containing head-to-tail cDNA dimers of HDV were inoculated intramuscularly into mice. Genomic-sense HDV RNA was detected in the injected muscle within 1 week and increased to substantial levels by week 7 postinjection. The intramuscular accumulation of HDV RNA was determined to be the direct result of viral RNA replication by three lines of evidence: (i) injected tissues also accumulated antigenomic-sense HDV RNA, (ii) plasmid DNA that synthesized primary transcripts of antigenomic sense also led to the accumulation of genomic-sense HDV RNA, and (iii) injection of a cDNA dimer defective in antigenomic RNA cleavage failed to produce detectable HDV RNA in muscle. Immunohistochemical analysis of injected muscle demonstrated the presence and nuclear localization of hepatitis delta antigen in myocytes. Finally, sera from DNA-injected mice contained antibodies specific for delta antigen, indicating the induction of an immunological response to the intracellularly expressed antigen. These findings demonstrated the ability of HDV RNA to replicate in skeletal muscle and provide a useful system for the study of HDV replication, delta antigen processing, and its presentation to the immune system in vivo. Furthermore, this system offers an efficiently replicating RNA as a potential vehicle for in vivo gene transfer.

Animals↗

Tegmental pontine hemorrhage with pure trigeminal motor impairment.

We report a patient with a right dorsolateral pontine syndrome including right masticatory weakness without facial hypesthesia. Brain computed tomography showed a right dorsolateral pontine hemorrhage. Blink reflex study indicated preservation of spinal tracts and sensory nuclei of the trigeminal nerve. Right masseter electromyography revealed denervation. This patient provides a good correlation between clinical, radiological and electrophysiological findings and nuclear organisation of the trigeminal nerve.

Aged↗

Friedreich's ataxia presenting with pure sensory ataxia: a long-term follow-up study of two patients.

We describe two patients with Friedreich's ataxia whose presenting symptomatology was for years progressive tabetic ataxia. Based upon the initial clinical, electrophysiological and nerve biopsy data, a diagnosis of idiopathic sensory neuropathy was established. Subsequent examination of the kin showed that three sisters of case 1 had Friedreich's ataxia. Upon serial clinical and electrocardiographic study, both patients eventually developed a florid Friedreich's ataxia, including cardiomyopathy. Our findings indicate that at onset Friedreich's ataxia may be indistinguishable from sensory neuropathy and also that serial examination and investigation of kinship are essential steps for accurate diagnosis.

Adult↗