Peak nasal inspiratory flow in chronic obstructive pulmonary disease.

BACKGROUND: The nasal airflow in chronic obstructive pulmonary disease (COPD) is poorly characterized. Peak nasal inspiratory flow (PNIF) is a valuable instrument for assessing nasal airflow and the effect of pulmonary pathology such as COPD on PNIF remains unknown. To test the hypothesis that nasal airflow is reduced in COPD, we assessed airflow using PNIF in COPD and a control group. We also explored whether there is an association between COPD, chronic rhinosinusitis without nasal polyps (CRSsNP), and other predefined covariates with PNIF. METHODOLOGY: Ninety patients with COPD and 67 controls underwent PNIF and spirometry. The associations between PNIF and COPD and pre-bronchodilator forced expiratory volume in the first second (FEV1) (% predicted) were assessed by multivariable linear regression in two separate models. RESULTS: PNIF was significantly lower in the COPD group than in the control group. Multivariable linear regression showed that COPD and pre-bronchodilator FEV1 (% predicted) were significantly associated with lower PNIF after adjustment for age, sex, CRSsNP, weight and height. CRSsNP was not associated with PNIF in either of the adjusted regression analyses. CONCLUSIONS: PNIF is lower in COPD than in a control group. The finding of a low PNIF in the absence of disease in the upper airways may be due to obstructive lower airways diseases and special care should be taken when interpreting PNIF values in patients with COPD or reduced FEV1.

Olfaction in COPD.

BACKGROUND: Olfaction is poorly characterized in COPD. To test the hypothesis that olfaction is reduced in COPD, we assessed olfaction with the "Sniffin' Sticks" test and a questionnaire addressing olfaction in COPD and a corresponding control group in respect to age and sex. We also explored whether there is an association between COPD, chronic rhinosinusitis without nasal polyps (CRSsNP), and other predefined covariates with olfactory function. METHODOLOGY: Olfactory function was assessed by the score for threshold (T), discrimination (D) and identification (I), and the composite TDI score in the "Sniffin' Sticks" test and by self-reported evaluation of impaired olfaction and of "decreased sense of smell and taste" in the 22-item Sino-Nasal Outcome Test (SNOT-22) in 90 COPD patients and 93 controls. A clinical interview and ENT-examination with nasal endoscopy, skin prick test and spirometry with reversibility were performed. RESULTS: The TDI, D and I scores were significantly lower in the COPD group than in the control group. The T score was not significantly different between the two groups. Hyposmia and anosmia were present in up to 79% of patients with COPD. The prevalence of self-reported impaired olfactory function and for "decreased sense of smell and taste" - was more than two-fold greater in the COPD than in the control group. COPD, higher age, male sex and allergy were associated with a lower TDI score, while CRSsNP was not associated with the TDI score. CONCLUSIONS: COPD is associated with olfactory dysfunction and the underlying mechanisms for this dysfunction should be elucidated.

Positive symptoms and duration of illness predict functional laterality and attention modulation in schizophrenia.

OBJECTIVE: Dichotic listening (DL) performance in schizophrenia, reflecting hemispheric asymmetry and the functional integrity of the left temporal lobe, can vary with clinical characteristics. Previous studies have not taken the co-linearity of clinical variables into account. The aim of the present study was to evaluate the roles of positive symptoms and duration of illness in DL through Structural Equation Modeling (SEM), thus allowing for complex relationships between the variables. METHOD: We pooled patients from four previous DL studies to create a heterogeneous group of 129 schizophrenic patients, all tested with a consonant-vowel syllables DL procedure that included attentional instructions. RESULTS: A model where positive symptoms predicted a laterality component and duration of illness predicted an attention component in DL was confirmed. CONCLUSION: Positive symptoms predicted reduced functional laterality, suggesting involvement of left temporal lobe language processing. Duration of illness predicted impaired attention modulation, possibly reflecting the involvement of frontotemporal networks.

Human T-cell leukemia virus type 1 tax protein activates transcription through AP-1 site by inducing DNA binding activity in T cells.

Human T-cell leukemia virus type 1 (HTLV-1) Tax protein induces the expression of various family members of the transcription factor AP-1, such as c-Jun, JunD, c-Fos, and Fra-1, at the level of RNA expression in T cells. We examined the activity of Tax in transcription through AP-1-binding sites (AP-1 site) in T cells. Transient transfection studies showed that Tax activated the expression of a luciferase gene regulated by two copies of an AP-1 site in the human Jurkat T-cell line. Tax activates the expression of viral and cellular genes through two different enhancers: a cAMP-responsive (CRE)-like element and a kappaB element. Two Tax mutants differentially activated expression of these two elements. Tax703 preferentially activated the kappaB element but not the CRE-like one, whereas TaxM22 showed the reverse. In addition, Tax703 and Tax, but not TaxM22, converted cell growth of a mouse T-cell line from being interleukin (IL)-2-dependent to being IL-2-independent. Unlike the wild-type Tax, Tax703 and TaxM22 only weakly activated the AP-1 site in the T-cell line. Thus, Tax seems to activate the AP-1 site via mechanisms distinct from those of kappaB or CRE-like elements, and the activation of the AP-1 site is dispensable for IL-2-independent growth of CTLL-2. Electrophoretic mobility shift assays showed that Tax induced strong binding activity to an AP-1 site in CTLL-2, whereas Tax703 did not, indicating that the induction of binding activity to the AP-1 site is essential for the transcriptional activation by Tax. The binding complex induced by Tax in CTLL-2 contained JunD and Fra-2. Other AP-1 proteins were undetectable. Activation of transcription through the AP-1 site in Jurkat cells by JunD and/or Fra-2 was weak. c-Jun, JunB, and c-Fos activation was greater, although the level was still less than that with Tax. Thus, the induction of AP-1 mRNA by Tax may not be sufficient for a complete activation of AP-1 site by Tax. Our results suggest that Tax activates the transcription of cellular genes with AP-1 sites by inducing the DNA-binding activity of AP-1 proteins in T cells, a mechanism distinct from those of CRE-like and kappaB elements.

Interleukin-2-dependent but not independent T-cell lines infected with human T-cell leukemia virus type 1 selectively express CD45RO, a marker for persistent infection in vivo.

Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia. HTLV-1 is exclusively detected in CD45RO+ T-cells in infected individuals, but CD45RO is weakly expressed in HTLV-1-transformed T-cell lines in vitro. The aim of this study was to investigate the role of CD45RO in the persistent HTLV-1 infection in vivo. Flow cytometry showed that only two out of eight interleukin(IL)-2-independent HTLV-1-transformed T-cell lines expressed CD45RO, whereas all five IL-2-dependent ones expressed CD45RO, and the level of expression was higher in IL-2-dependent than in IL-2-independent cells. The high CD45RO expression in IL-2-dependent cell lines was not due to IL-2, since IL-2 had little effect on the expression of CD45RO in T-cell lines. Using western blotting, we showed that IL-2-dependent HTLV-1-transformed T-cell lines expressed a lower level of expression of the viral transcriptional regulatory protein Tax than IL-2-independent ones, and that the level of expression correlated inversely with that of CD45RO. However, the expression of Tax in one HTLV-1-negative T-cell line little affected the expression of CD45RO, suggesting that Tax at least alone does not suppress the expression of CD45RO in HTLV-1-infected T-cell lines, and that other viral or cellular factor(s) are probably involved in such suppression. Our results suggest that CD45RO+ Tax-low IL-2-dependent T-cell lines in vitro correspond to the persistent HTLV-1-infected cells in vivo, and HTLV-1-infected cells in vivo are immortalized in IL-2-dependent manner.

Activation of oncogenic transcription factor AP-1 in T cells infected with human T cell leukemia virus type 1.

Human T cell leukemia virus type 1 (HTLV-1) Tax protein transforms primary human T cells in vitro. We previously showed that Tax induces the expression of various family members of the transcription factor AP-1 such as c-Jun, JunD, c-Fos, and Fra-1 at the mRNA level in T cells. In this study, we have examined the ability of Tax to activate transcription through the AP-1-binding site (AP-1 site). A transient transfection study showed that Tax can activate transcription through the AP-1-binding site in a human T cell line, whereas any combination of AP-1 proteins did so much less than Tax, indicating that the activation of the AP-1 site by Tax may require a mechanism other than the induction of AP-1 mRNA. Fresh peripheral blood leukemia cells of all surveyed ATL patients displayed constitutive AP-1 DNA-binding activity, whereas no normal individuals did. However, the HTLV-1 genes, including tax, are not significantly expressed in fresh leukemia cells from ATL patients. Our present results suggest that activation of AP-1 occurs through Tax-dependent and -independent mechanisms in HTLV-1-infected T cells, which may play some roles in dysregulated phenotypes of HTLV-1-infected cells.

Contrasts in memory functions between adolescents with schizophrenia or ADHD.

Previous research on memory and schizophrenia has relied on a limited number of global memory measures instead of a comprehensive assessment of various memory components. In addition, little effort has been directed at examining memory functioning in patients with early-onset schizophrenia. Published research often lacks a relevant neuropsychiatric comparison group to control for attention difficulties. Patients with Attention Deficit Hyperactivity Disorder (ADHD) were included in the present study for this purpose. To our knowledge, a direct comparison of the two patient groups on memory functions has never been made. In the present study, both adolescents with schizophrenia and adolescents with ADHD were compared on a comprehensive memory test battery. Nineteen adolescents with schizophrenia were compared to 20 ADHD adolescents and 30 normally functioning adolescents on measures of working memory and long-term episodic memory, including tests of verbal and visual memory, free recall and recognition memory. The performance of the adolescents with schizophrenia was impaired as compared to the normal group on most of the memory measures. They performed significantly more poorly than the adolescents with ADHD on the visual memory tests. The ADHD group scored more impaired than the schizophrenia group on working memory tests with focus on distractibility. The findings suggest a general memory deficit among adolescents with schizophrenia related to both verbal and visual material. Impairment on the measures of visual memory is specific to schizophrenia and does not characterise the ADHD subjects.

Neuropsychological deficits in adolescent-onset schizophrenia compared with attention deficit hyperactivity disorder.

OBJECTIVE: Impaired neuropsychological performance involving abstraction-flexibility, memory, motor function, and attention has frequently been reported in schizophrenia as well as in attention deficit hyperactivity disorder (ADHD). This study represents an attempt to compare groups of adolescents with schizophrenia and ADHD on a comprehensive neuropsychological test battery. Such a comparison affords the opportunity to ascertain differences in the degree, profile, and specificity of impairments. METHOD: The performance of 19 adolescents with schizophrenia, 20 adolescents with ADHD, and 30 normal adolescents on a broad battery of cognitive tests was compared. RESULTS: The schizophrenic group showed the most pronounced deficits on tests of abstraction, visual memory, and motor function in comparison with the subjects with ADHD, while the ADHD subjects had the most pronounced deficits on measures of attention, verbal memory, and learning. CONCLUSIONS: The subjects with schizophrenia appeared to have a more general pattern of brain dysfunction, whereas the impairment of the ADHD subjects seemed to be relatively specific to tests associated with frontal lobe function.

Auditory laterality and selective attention: normal performance in patients with early-onset schizophrenia.

In this study, auditory laterality and selective attention were examined in patients with early-onset schizophrenia using a dichotic listening (DL) test. Deficient performance on this test has repeatedly been found in adult patients with chronic schizophrenia, indicating abnormalities in left hemisphere function. The hypothesis in the present study was that subjects with early-onset schizophrenia manifest deficits in DL test performance similar to adult chronic patients. A group of 19 patients with early-onset schizophrenia were compared with a group of 20 adolescents with attention-deficit hyperactivity disorder and a group of 30 normal adolescents. Results indicated no significant differences between the three groups on any of the measures. Alternative hypotheses are put forth to explain the findings, among them that deficits in DL performance may be secondary to long-time illness and/or drug treatment, and that these deficits may become apparent only after interaction with maturational neurodevelopmental changes during adolescence.

Covert visual attention in patients with early-onset schizophrenia.

The aim of the present study is to examine attentional costs (inhibition) in covert visual attention in a group of acutely ill adolescents with schizophrenia without long histories of neuroleptic treatment. Variations in reaction time were analyzed for possible age and sex differences. Adolescents with schizophrenia (n = 19) were compared to a group of ADHD subjects (n = 20) and a group of normally functioning adolescents (n = 30) on a measure of covert visual attention. The results support a hypothesis of abnormally rapid disengagement (reduced costs) in male adolescents with schizophrenia. Such an abnormality has also been found in adults with chronic schizophrenia. Whether this holds true for both sexes of adolescents with schizophrenia or is restricted to male subjects cannot be answered with certainty due to the small number of females with schizophrenia in our sample. Our findings indicate, however, that there are some general sex differences and some specific sex differences related to covert visual attention in adolescents with schizophrenia.

No vigilance deficit found in either young schizophrenic or ADHD subjects.

Vigilance deficits have been found in both schizophrenic and ADHD subjects. The two patient groups have never been directly compared on any vigilance measure, however. In the present study 20 early-onset schizophrenics were compared to 20 ADHD adolescents on a Degraded Stimulus Continuous Performance Test (DS-CPT). A comparison group of 30 normal adolescents was also included. Results showed no significant differences between the three groups on any of the DS-CPT measures. Different hypotheses are put forth to explain the findings, among them that the task may be insensitive to identifying sustained attention deficits in adolescent populations.

Backward-masking deficit in adolescents with schizophrenic disorders or attention deficit hyperactivity disorder.

OBJECTIVE: Backward masking is a cognitive task that involves the earliest phases of visual information processing. Disrupted task performance caused by a visual mask has been found repeatedly in schizophrenic patients; however, the specificity to schizophrenia of deficits in backward masking has received only limited study. METHOD: In this study 20 patients with early-onset schizophrenic disorders were compared to 20 adolescents with attention deficit hyperactivity disorder (ADHD) and 30 normal adolescents on a two-digit identification task in three backward-masking conditions: no mask, a short stimulus interval (33.0 msec), and a long stimulus interval (49.5 msec). RESULTS: The performance of the two groups of patients was similar, and both groups showed a statistically significant masking deficit after the long stimulus interval and a nearly significant deficit after the short stimulus interval in comparison with the normal subjects. CONCLUSIONS: Increased vulnerability to the masking stimulus was confirmed in schizophrenic subjects, but it is not specific to schizophrenia and is not accounted for by psychotic symptoms alone, since the subjects with ADHD performed similarly.

Neutralizing epitope on penetration protein of vaccinia virus.

The monoclonal antibody 2D5 neutralized vaccinia virus by preventing penetration of the virus and reacting with VP23-29K. The conformation of the VP23-29K was maintained by a disulfide bond(s), and the 2D5mAb reacted stronger with the nonreduced 23-kDa form than with the reduced 29-kDa form. We selected several escape mutants. Sequences of the A17L genes, which were thought to encode the VP23-29K, did not show cognate mutation. Genomic DNA of a 2D5mAb-resistant mutant (M4) was cleaved with HindIII, and all the fragments were introduced into parental IHD-J strain vaccinia virus by transfection. Only the L fragment produced a 2D5mAb-resistant virus. Dissection of the L fragment and subsequent transfection revealed that the L1R gene induced the 2D5mAb-resistant virus. The 2D5mAb-resistant mutants showed a consensus G to A conversion at nucleotide 101 of their LIRs which would replace asparatic acid 35 with asparagine. Ishibashi-111 strain mousepox virus spontaneously resistant to 2D5mAb also had the same sequence at this region. Moreover, the VP23-29K was myristoylated as predicted by the L1R gene. The coding gene of the VP23-29K was L1R.

Expressed emotion, communication deviance and schizophrenia. An exploratory study of the relationship between two family variables and the course and outcome of a psychoeducational treatment programme.

The relationship between expressed emotion (EE) and communication deviance (CD), and outcome in a group of early-onset schizophrenics after 2 years of psychoeducational treatment was examined. Patients' parents were assessed on EE and CD before and after the 2-year period. Outcome was measured by Global Assessment Scale (GAS) and relapse rate. Results showed that the correlation between CD and outcome was higher than between EE and outcome. In most of the patients who improved their GAS score during the treatment programme, their parents changed from high to low EE. CD proved to be more resistant to psychosocial intervention than EE.

Identification of a vaccinia virus penetration protein.

A vaccinia virus structural protein responsible for infection was identified by monoclonal antibodies (mAb). Two mAbs (2D5 and 8C2) neutralized the virus at a dilution of about 10(5). The 2D5 mAb reacted with VP29K under standard immunoblotting conditions and with a 23-kDa protein when virus was dissociated under nonreducing conditions. The 8C2 mAb reacted with the 23-kDa protein, but not with VP29K. Two-dimensional electrophoresis demonstrated that the 23-kDa protein was the nonreduced form of VP29K. Since they possess the same N-terminal amino acid sequence, the protein was renamed VP23-29K. The gene that encoded it was HindIII A17L ORF. The VP23-29K-dependent process of infection did not occur during the adsorption phase at 4 degrees, and trypsin-treated virus could complete the process within 10 min at 37 degrees. One half of the trypsin-treated intracellular mature virus (IMV) achieved the process within 20 min, but for normal IMV this time period was 2 hr. VP23-29K had function for the early step of penetration, and the functional site in the nonreduced 23-kDa form was masked to some extent in normal virus. The late cell fusion by the fusion positive (F+) D1 mutant proceeded in neutral pH. Cells infected with F- IHD-J strain virus did not fuse, but a short treatment with pH 5 medium developed cell fusion. Both of the cell fusions were inhibited by the 2D5 and 8C2 mAbs. Virion VP23-29K was suggested to be the fusion protein for the early penetration and the late cell fusion phases of vaccinia infection cycle.

N-terminal amino acid sequences of vaccinia virus structural proteins.

The N-terminal amino acid sequences of vaccinia virus structural proteins were determined by direct sequencing following separation of the proteins of purified intracellular mature virus by SDS-polyacrylamide gels. By comparing the sequences obtained with the published vaccinia virus DNA sequences, specific open reading frames (ORFs) were identified. The structural proteins were encoded by the ORFs of HindIII, A3L (VP57K, 32K), A10L (VP62K, VP28K, VP22K), A12L (VP10K, VP4K), A13L (VP14K), A14L (VP17-25K), A17L (VP23-29K), A27L (VP13.8K), D8L (VP32K), H3L (VP34-37K), L4R (VP27K), G7L (VP16K), and 15L (VP13K). Four virus membrane proteins contained transmembrane signals. The N-termini of proteins indicated four types of cleavages. Ala-Gly-specific cleavage associated with products of six ORFs. Phe-specific cleavage was found in two, Met-specific in three, and Arg-specific in the product of one ORF. Ala-Gly-specific cleavage processes seven core proteins encoded by five ORFs and one membrane protein. The Met- and Arg-specific cleavages are suggested to be nonessential for virus assembly because the major portions of the target membrane proteins remain unaffected.

Application of total quality management to unit-based quality assessment and improvement.

The paradigm is shifting in health care. The current emphasis is on total quality management (TQM). The authors describe a model, Quality in Daily Work (QIDW), which may be used to assist in the implementation of TQM at the unit level. QIDW is patterned after Juran's Trilogy of quality planning, quality control, and quality improvement.

Autonomous staff selection teams.

Although some other organizations encourage staff input into employee selection, the advanced care department at Bellin Hospital in Green Bay, Wisconsin has taken this concept to a new level by implementing an autonomous interview team. This team is empowered to make hiring decisions for all positions within the department without management influence or interference.