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.

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.

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.

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.

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.

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.

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.

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.

Reversible inactivation and reactivation of vaccinia virus by manipulation of viral lipid composition.

The role of phospholipids in vaccinia virus was investigated by substituting viral lipids with specific phospholipids. Treatment of virus with sodium dodecyl sulfate, sodium deoxycholate, or Nonidet-P40 (NP-40) resulted in almost complete removal of viral lipid and led to inactivation of the virus. The inactivation induced by the former two was irreversible, but NP-40-treated virus was reactivated upon reassociation with phospholipids. Individual phospholipids, including phosphatidylserine (PS), phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysolecithin, sphingomyelin, and acyl bis(monoacylglycero)phosphate (ABMP), were tested for ability to reactivate NP-40-treated virus. Reactivation was induced only by PS. The infectivity of virus that had been treated with NP-40 and then with PS was unstable; the reactivated virus was inactivated within a short period. It was also very sensitive to trypsin. Treatment of NP-40-treated virus with mixtures of PS and ABMP yielded virus that was more resistant to spontaneous and trypsin-induced inactivation. Thus, PS appears to be an essential for infectivity and ABMP appears to play a supplementary role for maintenance of infectivity, perhaps by protecting against inactivating factors.

Target antigen of vaccinia-infected cells recognized by virus-specific cytotoxic T lymphocytes.

A vaccinia-specific target antigen for recognition of anti-vaccinia cytotoxic T lymphocytes (CTL) was found to be formed on the surface of infected cells through two distinct processes. In the first phase, the expression of the target antigen was dependent on the dose of inoculated virus, without specific protein synthesis. The target antigen seems to be produced by virus-cell fusion. In the second phase, the expression of the target antigen was accompanied by synthesis of an early protein. In spite of the difference in their mode of expression, the first-phase and the second-phase target antigens were cross-reactive in cytotoxicity inhibition assays. Cowpox virus, CPR Cl strain, brought about a lower response than vaccinia virus, IHD-J strain, in both sensitization of CTL and formation of CTL-susceptible cells at both the first and the second phase. The cross-reactive, but inefficient, recognition of anti-vaccinia CTL for cowpox-infected cells suggested a slight difference in the target antigens of the two viruses. Attempts to identify the target antigen were then made by comparing the polypeptide composition of vaccinia virus, cowpox virus, and their recombinants. SDS-PAGE analysis of trypsin-activated viruses revealed 44K (cowpox)/45K (vaccinia) polypeptides which corresponded to the difference in target cell formation. Trypsinization of the viruses also increased the ability of the virus to induce the production of CTL-susceptible target cells.

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.

Modification of vaccinia virus penetration proteins analyzed by monoclonal antibodies.

Modifications induced in structural vaccinia virus proteins that elicit the high infectious state by virus activating treatments involving trypsin and phosphatidylserine were analyzed using antivaccinia monoclonal antibodies (MABs). MABs reactive against each of the five outer layer proteins (VP54K, 34K, 32K, 29K, and 17K-25K) neutralized infectivity. VP54K possesses at least two neutralizing epitopes. Treatment with trypsin or with isolated plasma membrane cleaved VP54K into TVP41K carrying epitope A and removed a fragment containing epitope B from the virus. MABs against either of the epitopes could neutralize the virus. The exposure of epitope A concomitantly activated virus infectivity, and it was an essential step of penetration. MABs against VP17K-25K reacted more efficiently with trypsin-treated virus than with untreated virus, but the size of VP17K-25K was not affected by trypsin; this finding indicated that trypsin treatment rendered the VP17K-25K epitopes more accessible to antibody and hence to neutralization. MABs against VP32K and VP29K neutralized infectivity to the same extent irrespective of the state of activation. Virus treated with phosphatidylserine (PS) was neutralized more efficiently by MAB against VP34K than untreated virus, but the amount of antibody that reacted with the virus was the same before and after treatment with PS. Phosphatidylserine did not modify epitope structure itself, but it activated the function of VP34K. It was concluded that blocking of the functions attributed to any of the five proteins resulted in neutralization of virus infectivity, and treatment with trypsin and phosphatidylserine activates infectivity of vaccinia virus by modifying three of them (VP54K, VP34K, VP17K-25K) with characteristic behavior for each protein.

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.

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.

The activation of vaccinia virus infectivity by the transfer of phosphatidylserine from the plasma membrane.

Purified vaccinia virus usually contains a large proportion of noninfectious virus which can be converted to infectious virus by incubation with purified plasma membrane. This activating reaction which is mediated by a heat stable component of the membrane has been studied. A suspension of liposomes containing the lipids extracted from plasma membrane of either KB cells or mouse RBCs activated the noninfectious virus in the same manner as heated plasma membrane. The phospholipid fraction of the KB cell lipids had the activating ability, but neither neutral lipid nor glycolipid fraction activated the virus. Liposomes containing phosphatidylserine activated the virus, whereas other tested phospholipids, including phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine, and sphingomyelin had no effect on virus infectivity. Lysolecithin reduced the infectivity. Treatment with isolated plasma membrane or liposomes increased hydrophobicity of the virus slightly, but did not change its density. Analysis of activated and then purified virus showed that all phospholipid species in the coincubated plasma membranes and liposome samples were transferred to the virus. The transfer was not a phospholipid exchange reaction but a one-way net transfer, and took place rapidly at 37 degrees to reach saturation within 1 hr of coincubation. Neither activation of virus nor transfer of phospholipid occurred when the mixture was incubated at a temperature below 8 degrees. The virus has great ability to extract phospholipids from coincubated lipid bilayer membranes, and association with phosphatidylserine gives the virus high infectivity.

Epitope mosaic on the surface proteins of orthopoxviruses.

Epitopes on the surface components of orthopoxviruses were analyzed with monoclonal antibodies (MAbs) against monkeypox and vaccinia viruses by enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), radioimmunoprecipitation (RIP), and competitive binding inhibition assay (CBIA). When compared by ELISA, three vaccinia virus strains exhibited a similar reactivity to 99 tested MAbs despite their remote passage history. All five isolates of monkeypox virus closely resembled one another, irrespective of the host species (human, monkey, squirrel) from which they were isolated. Taterapox virus reacted similar to vaccinia virus against 97 of the 99 tested MAbs, and reacted with 2 MAbs which were cross-reactive with monkeypox and mousepox. Mousepox and cowpox viruses reacted with these MAbs in a species-specific manner: MAbs reactive to cowpox virus distinctly differ from those reactive to mousepox virus. Of the 99 tested MAbs, 32 reacted with all the 11 tested orthopoxviruses, indicating that the corresponding epitopes existed in all the viruses. Fifty-four MAbs reacted with two or more virus species and were classified as partially common MAbs. Eight MAbs were apparently type-specific for monkeypox, and five were specific for vaccinia and taterapox viruses. No strain-specific epitope was detected. Sera of monkeypox-infected patients, when analyzed by CBIA, interfered with the binding of monkeypox-specific MAb H12C1 but not of vaccinia-specific MAb G6C6. Sera of monkeypox-infected patients who had been vaccinated competed against both MAbs, demonstrating the original antigenic sin phenomenon. The two MAbs could distinguish between the sera of monkeypox patients and those of vaccinated persons. However, the serum of a smallpox patient was competitive against these apparently vaccinia- or monkeypox-specific MAbs. Three of the eight monkeypox-specific epitopes were recognized by the above CBIA test, which suggests that they also exist in smallpox virus. The mosaic-like combination of common epitopes and the small number of type-specific epitopes manifested the antigenic characteristics of orthopox viruses. The species boundary was obscured due to the partially common epitopes, but the total composition of epitopes was stable enough to maintain the antigenic species-specificity. The mutual relationship of the orthopoxviruses was visualized in a three-dimensional network.

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.