Milk-induced wheezing in children with asthma.

BACKGROUND: Food allergy has been gaining increasing attention, mostly as causing gastrointestinal and cutaneous reactions. Its role in asthma seems to be under-recognised. OBJECTIVES: This study's aim is to explore the frequency of involvement of a common food, namely cow's milk, in childhood asthma. METHODS: 32 children (5 months to 11 years; median 24 months; mean 34 months) with asthma and a suspected history of cow's milk allergy were studied. They underwent skin prick testing (SPT) and specific IgE (sIgE) testing to whole cow's milk (WCM), casein, α-lactalbumin, and ß-lactoglobulin, followed by single-blind oral milk challenge. RESULTS: Reactions to milk challenge occurred in 12 (37.5%) including wheezing in 5 (41.7%, or 15.6% of the whole group). Children who developed wheezing at the time of challenge were younger than those who had negative challenge (23.0 months vs. 34.8 months). Challenge was positive in 33.3% of subjects who had a positive SPT, and SPT was positive in 50% of challenge-positive subjects. Regarding sIgE, challenge was positive in 26.7% of sIgE-positive subjects, and sIgE was positive in 33.3% of challenge positive subjects. Skin or serum testing with individual protein fractions did not seem to add significant advantage over testing with WCM alone. CONCLUSION: This study shows that cow's milk can cause wheezing in children with asthma. Although SPT seemed to be more reliable than sIgE testing, both had suboptimal reliability. It is worth considering possible milk allergy in children with asthma, particularly when poorly controlled in spite of proper routine management.

Poliovirus host range is determined by a short amino acid sequence in neutralization antigenic site I.

The mouse-adapted strain of poliovirus type 2 (Lansing) induces fatal poliomyelitis in mice after intracerebral inoculation, whereas mice inoculated with poliovirus type 1 (Mahoney) show no signs of disease. Previous work indicated that the adaptation to mouse virulence is associated with the viral capsid proteins and that mutations in neutralization antigenic site I of poliovirus reduce neurovirulence of the Lansing strain in mice. The role of antigenic site I in mouse neurovirulence was further explored by constructing an antigenic hybrid virus. Six amino acids in antigenic site I of the Mahoney strain were replaced with a sequence specific for the Lansing strain by using a mutagenesis cartridge. The hybrid virus was neutralized by polyclonal antisera elicited by the type 1 and type 2 strains of poliovirus and by neutralizing monoclonal antibodies directed against antigenic site I of type 2 virus. The hybrid virus induced paralytic disease in mice, an observation demonstrating that a short sequence of amino acids in antigenic site I is an important determinant of poliovirus host range. Antigenic site I may be involved in attachment of poliovirus to cells of the mouse central nervous system.

Phaseolin gene from bean is expressed after transfer to sunflower via tumor-inducing plasmid vectors.

Sequences coding for the bean seed protein phaseolin were inserted into transferred DNA regions of tumor-inducing plasmids. Constructions were devised in which the coding region of phaseolin was fused in the correct reading frame with the coding region of octopine synthase and placed under the transcriptional control of the octopine synthase promoter. Other plasmids were prepared to permit expression of the phaseolin-encoding sequences from the flanking phaseolin promoter region. The RNA transcribed in sunflower cells transformed with these constructions was characterized by hybridization procedures, SI nuclease mapping, and by translation in vitro of extracted RNA. These tests showed that the genomic intervening sequences were correctly excised. Immunoreactive phaseolin polypeptides were detected by enzyme-linked immunosorbent assay and by antibody hybridization to electrophoretically separated protein extracts of sunflower tissues isolated from crown gall tumors and of transformed sunflower cells grown in tissue culture. These results demonstrate the expression of a plant gene after transfer to a taxonomically distinct botanical family.

The hepatitis C virus internal ribosome entry site adopts an ion-dependent tertiary fold.

Hepatitis C virus (HCV) contains an internal ribosome entry site (IRES) located in the 5' untranslated region of the genomic RNA that drives cap-independent initiation of translation of the viral message. The approximate secondary structure and minimum functional length of the HCV IRES are known, and extensive mutagenesis has established that nearly all secondary structural domains are critical for activity. However, the presence of an IRES RNA tertiary fold and its functional relevance have not been established. Using chemical and enzymatic probes of the HCV IRES RNA in solution, we show that the IRES adopts a unique three-dimensional structure at physiological salt concentrations in the absence of additional cofactors or the translation apparatus. Folding of the IRES involves cooperative uptake of magnesium and is driven primarily by charge neutralization. This tertiary structure contains at least two independently folded regions which closely correspond to putative binding sites for the 40 S ribosomal subunit and initiation factor 3 (eIF3). Point mutations that inhibit IRES folding also inhibit its function, suggesting that the IRES tertiary structure is essential for translation initiation activity. Chemical and enzymatic probing data and small-angle X-ray scattering (SAXS) experiments in solution show that upon folding, the IRES forms an extended structure in which functionally important loops are exposed. These results suggest that the 40 S ribosomal subunit and eIF3 bind an HCV IRES that is prefolded to spatially organize recognition domains.

Neuropathological and neuropsychological changes in "normal" aging: evidence for preclinical Alzheimer disease in cognitively normal individuals.

The presence of diffuse or primitive senile plaques in the neocortex of cognitively normal elderly at autopsy has been presumed to represent normal aging. Alternatively, these patients may have developed dementia and clinical Alzheimer disease (AD) if they had survived. In this setting, these patients could be subjects for cognitive or pharmacologic intervention to delay disease onset. We have thus followed a cohort of cognitively normal elderly subjects with a Clinical Dementia Rating (CDR) of 0 at autopsy. Thirty-one brains were examined at postmortem according to Consortium to Establish a Registry for Alzheimer Disease (CERAD) criteria and staged according to Braak. Ten patients were pathologically normal according to CERAD criteria (1a). Two of these patients were Braak Stage II. Seven very elderly subjects exhibited a few primitive neuritic plaques in the cortex and thus represented CERAD 1b. These individuals ranged in age from 85 to 105 years and were thus older than the CERAD la group that ranged in age from 72 to 93. Fourteen patients displayed Possible AD according to CERAD with ages ranging from 66 to 95. Three of these were Braak Stage I, 4 were Braak Stage II, and 7 were Braak Stage III. The Apolipoprotein E4 allele was over-represented in this possible AD group. Neuropsychological data were available on 12 individuals. In these 12 individuals, Possible AD at autopsy could be predicted by cognitive deficits in 1 or more areas including savings scores on memory testing and overall performance on some measures of frontal executive function.

Inactivation of a yeast transactivator by the fused HIV-1 proteinase: a simple assay for inhibitors of the viral enzyme activity.

The human immunodeficiency virus type 1 (HIV-1) proteinase (PR) and its flanking sequences have been fused in frame between the DNA-binding domain and the transcription-activation domain of the yeast protein, GAL4. As has been shown before with the 3C proteinase of Coxsackie virus B3 (CVB3) [Das Mahapatra et al., Proc. Natl. Acad. Sci. USA 89 (1992) 4159-4162], the GAL4::PR fusion protein retains its GAL4 function, providing the PR is inactive. When PR is active, its autocatalytic activity in the hybrid protein is shown to inactivate the transactivation function of GAL4. This provides a simple assay to monitor PR activity. A dose-dependent effect of a potent PR-specific inhibitor is demonstrated in this system and illustrates the sensitivity of the assay. The assay is used for high throughput screening to identify novel inhibitors of the viral PR, and provides a method to generate and analyze mutants and revertants of the PR.

Nucleotide sequence and characterization of a gene encoding the phytochrome polypeptide from Avena.

We have isolated and characterized a gene encoding the phytochrome polypeptide of Avena. Based on nucleotide sequence identity with previously sequenced cDNA clones this gene is designated as type 3 (phy3). The gene is about 5.9 kb long with six exons and five introns, one each of the latter in the 5' and 3'-untranslated regions. The largest exon encodes the entire 74-kDa, chromophore-bearing, N-terminal domain of the photo-receptor postulated to be directly involved in its mechanism of action. The transcription start point, identified by mung-bean nuclease digestion, is located 24 to 35 bp downstream from a tandem TATA box. Sequence elements homologous to a number of motifs implicated as upstream regulatory elements in other genes are present in the 5'-flanking DNA of phy3. Particularly intriguing are three elements at positions -140, -470 and -650. These elements share homology with the 'GT' motif postulated to be a component of the light-regulatory element of genes encoding the small subunit of ribulose bisphosphate carboxylase.

Use of a recombination-deficient phage lambda system to construct wheat genomic libraries.

The poor cloning efficiency of wheat (Triticum aestivum cv. Yamhill) DNA in conventional cloning vectors has previously prevented the preparation of complete genomic libraries. We show here that while wheat DNA does not clone efficiently using the vector Ch4A, it can be cloned efficiently using Ch32. Ch32 clones are red- gam+ and therefore can be propagated on recombination-deficient hosts. These results suggest that instability of wheat sequences in conventional lambda vector systems has frustrated previous attempts to prepare libraries.

Side effects of light therapy in seasonal affective disorder.

The authors report the frequency of side effects of light therapy in 105 patients with seasonal affective disorder treated with three intensities of light. Common symptoms to emerge during treatment were headache (19%), eyestrain (17%), and feeling "wired" (14%). There was no relationship between side effects and intensity of light used.

A multicenter study of the light visor for seasonal affective disorder: no difference in efficacy found between two different intensities.

Fifty-five patients with winter seasonal affective disorder (SAD) were treated with a light visor, a newly developed portable light-delivery system, in a controlled parallel design. A dim (400 lux) visor was compared with a bright (6000 lux) visor for either 30 or 60 minutes in the morning for 1 week. Response rates for these two treatments were 36% and 56%, respectively; the duration of treatment sessions did not affect outcome. There was no evidence that the brighter visor was superior in efficacy to the dimmer one. Significantly greater relapse occurred following withdrawal of the dimmer visor. Alternative explanations for these findings are that the light visor is acting as a placebo or that it is equally effective over a wide range of intensities.

Piperazine-based CCR5 antagonists as HIV-1 inhibitors. II. Discovery of 1-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4- methyl-4-[3(S)-methyl-4-[1(S)-[4-(trifluoromethyl)phenyl]ethyl]-1-piperazinyl]- piperidine N1-oxide (Sch-350634), an orally bioavailable, potent CCR5 antagonist.

Truncation of the original piperidino-2(S)-methyl piperazine lead structure 2, from a family of muscarinic antagonists, gave compound 8 which has improved selectivity for the HIV-1 co-receptor CCR5 over muscarinic receptors. Further optimization for pharmacokinetic properties afforded Sch-350634 (1), a prototypical piperazine-based CCR5 antagonist, which is a potent inhibitor of HIV-1 entry and replication in PBMCs. The title compound (1) has excellent oral bioavailability in rat, dog, and monkey.

SIVmac expressing hybrid envelope proteins containing HIV-1 V3 and/or C4 sequences is not competent for replication.

The V3- and C4-coding regions in the envelope gene of the infectious, pathogenic SIVmac239 clone were replaced by the corresponding HIV-1 sequences. Viral particles were obtained after transfection of COS-1 cells. Chimeric SIVmac constructs were not replication competent in the human T cell lines CEMx174, AA2, H9, and MT-4 or in primary cultures of rhesus monkey peripheral blood mononuclear cells. The lack of infectivity of the hybrid constructs was associated with inefficient proteolytic processing of the gp160env precursor. Unlike the modular nature of some proteins, gp120 appears to be a highly ordered molecule whose function is dependent on the integration of many discontinuous, interactive regions.

IQ scores of treatment-resistant schizophrenia patients before and after the onset of the illness.

In this study we examined the correlations of actual pre-morbid IQ scores (obtained from routine educational assessments) and estimated current IQ scores in 27 treatment-resistant schizophrenia patients. Pre-morbid (mean = 93) and current (mean = 83) IQ scores were significantly correlated (r = 0.807, P < 0.0001), while duration of illness (10-40 years) was unrelated to the magnitude of IQ score decline (r = -0.103, P = 0.575). These data suggest that pre-morbid IQ test scores are highly predictive of post-morbid scores.

Light visor treatment for seasonal affective disorder: a multicenter study.

The effectiveness of light therapy in seasonal affective disorder (SAD) was evaluated in 105 subjects across five centers. Three intensities of light (60 lux, 600 lux, and 3500 lux) were used in a 2-week randomized, parallel design. There was no significant difference in antidepressant efficacy of the three intensities of light. All three intensities produced a similar frequency of antidepressant response to each other and to that reported in previous studies. There were site differences in the severity of depression during light treatment, but diagnosis and medication status did not affect antidepressant response. These findings suggest that light therapy has an antidepressant action by a nonspecific effect or that light is biologically active in the treatment of SAD across a wide range of intensities.

Use of health services by men with and without antisocial personality disorder who are alcohol dependent.

In a sample of 104 medically stable male veterans with alcohol dependence, rates of health service utilization were compared for 48 patients with a primary diagnosis of antisocial personality disorder and 56 patients without this diagnosis. Patients were diagnosed using DSM-IV lifetime criteria; previous utilization of health services was based on self-reports. Although a similar proportion of both groups reported previous service use, patients with antisocial personality disorder reported using more substance abuse treatment services than those with a primary diagnosis of alcohol dependence. Between-group multiple regression analysis showed that an earlier age at onset of alcoholism and a history of a comorbid substance-induced mental disorder best predicted higher rates of use of substance abuse treatment.

Diagnostic status and treatment recommendations for Persian Gulf War Veterans with multiple nonspecific symptoms.

BACKGROUND: Unexplained symptoms have frequently been observed in deployed Persian Gulf War veterans (GWVs). Using factor analysis, the Centers for Disease Control and Prevention (CDC) has established criteria for Gulf War illness (GWI). We report here on the prevalence of GWI, identify comorbidities, and compare these with those of veterans without GWI. METHODS: GWVs who consented to complete questionnaires and laboratory measures were given complete physical and mental health examinations. Outcome measures included CDC criteria for GWI, the Medical Outcomes Study Short Form 36 (SF-36), clinical and laboratory evaluations, and structured psychiatric interviews. RESULTS: One hundred twenty GWVs were enrolled, and 89 received complete physical and mental health examinations; 83% met CDC criteria for GWI. Veterans with GWI (1) were older, (2) reported more combat exposure, (3) scored higher on measures of depression, post-traumatic stress disorder, and fibromyalgia, and (4) had poorer health-related quality of life. More than half had anxiety or depressive disorders, and 93% had at least one medical and/or psychiatric diagnosis. The SF-36 predicted mental health status with a positive predictive value of 81.58. By adding the Hamilton D rating for depression, the positive predictive value increased to 88.57. INTERPRETATION: The CDC criteria accurately identified GWVs negative for GWI. Most GWVs were positive for GWI. Neither CDC criteria nor CDC severity rankings distinguish between veterans with psychiatric syndromes and those without: both groups endorsed the same symptoms. More than half of those with GWI had a treatable anxiety or depressive disorder. The SF-36 was a valid predictor of mental health status, particularly when paired with the Hamilton depression interview.

When staff are assaulted. A nursing consultation support service.

Increasing patient to staff assaults led to the development of a Nursing Consultation Service, which can respond to the needs of assault victims and set the tone for institutional attitudes of nonblaming concern. A member of the consultation service meets with each known assault victim to review the incident, offer support, and provide assistance in addressing issues aroused by the incident. Implementation of this service and the use of a continuous monitor to track assault incidents is vital to highlight problem areas and develop assault prevention strategies.

Estudio de la prevalencia de enfermedades alérgicas referidas por dos grupos poblacionales de la ciudad de Bahía Blanca / Study of the prevalence of allergic diseases refered by two groups of population in the City of Bahia Blanca

Fundamento. La polución biológica natural puede causar o agravar procesos alérgicos. En la ciudad de Bahía Blanca se realizan monitoreos continuos de granos de polen desde 1994. Sin embargo, al no contar con información sistematizada sobre las enfermedades alérgicas, se desconoce si existe relación entre los efectos de la polución y la prevalencia de éstas en la población local. Objetivo. Conocer la prevalencia de enfermedades alérgicas y síntomas asociados en dos grupos poblacionales de la ciudad de Bahía Blanca. Lugar. Municipalidad de Bahía Blanca y Universidad Nacional del Sur. Diseño. Estudio de corte transversal con modalidad de encuesta, tomando una muestra representativa de cada población. Población. Empleados municipales y población universitaria. Método. Fue elaborado un cuestionario ad hoc, incluyendo preguntas del cuestionario ISAAC. Para todos los análisis se utilizó el software R, con el objetivo de realizar una regresión logística para el análisis de los resultados obtenidos. Para analizar el riesgo de padecimiento se utilizaron odds ratio y su correspondiente valor p (IC95% y un error del 2%). Resultados. El 22,72% de los encuestados refirió padecer alguna enfermedad alérgica diagnosticada. El 53,13% de quienes manifestaron síntomas no declararon padecer enfermedad. Se observó asociación estadísticamente significativa entre conjuntivitis y poseer mascotas (OR=2,5; p=0,02); y entre SIR y presencia de humedad en las paredes (OR=1,8; p<0,05). La regresión logística mostró asociación entre padecer enfermedad alérgica y antecedentes familiares de las mismas (p=3,97e­16) y entre padecer asma o SIA y el hábito de fumar (p=0,0002). Conclusiones. Las prevalencias encontradas para cada enfermedad alérgica indagada y sus síntomas coinciden con las halladas en estudios previos en la ciudad. Existe un alto subdiagnóstico manifestado en la referencia de síntomas asociados.(AU)

Background. The natural biological pollution can cause or exacerbate allergies. A continuous monitoring of pollen grains is performed in Bahía Blanca city since 1994. However, due to the lack of systematic information of these allergic diseases it is unknown whether there is or not a relationship between pollution effects and disease prevalence in the local population. Objective. Determine the prevalence of allergic diseases and its associated symptoms in two groups of people in Bahía Blanca's city. Location. Bahía Blanca's city hall and National University of the South. Design. Cross-sectional study, implementing a survey and taking a representative sample of each group. Population. Municipal employees and university population. Method. It was elaborated an ad hoc survey, including questions from the ISAAC questionnaire. The R software was used for all the analysis, in order to perform a logistic regression analysis. The odds ratio and its corresponding p value (CI95% and 2% error) were used in order to analyze the diseases index. Results. The 22.72% of the interviewed mentioned to suffer some diagnosed allergic disease. The 53.13% of those who showed symptoms denied suffering from any disease. Statistically significant association was observed between conjunctivitis and own pets (OR=2.5; p=0.02); and between SIR and the presence of damp walls (OR=1.8; p<0.05). The logistic regression analysis showed an association between allergic disease and family history of the same disease (p=3.97 e­16) and between asthma or SIA and smoking habits (p=0.0002). Conclusions. The prevalence found for each allergic disease and its investigated symptoms agreed with those previously found in other local studies. There was a high sub-diagnosis manifested in reference to associated symptoms.(AU)