Scrapie-associated tubulofilamentous particles in scrapie hamsters.

Examination of thin sections from the cerebral cortex of scrapie-infected hamster brains revealed characteristic circular 26-30 nm diameter tubulofilamentous particles, identical to those previously described in both experimentally induced scrapie in mice, hamsters and natural scrapie of sheep, bovine spongiform encephalopathy and human Creutzfeldt-Jakob disease and mice and chimpanzees infected with Creutzfeldt-Jakob disease. Longitudinal forms of tubulofilamentous particles were also observed in dendrites and myelinated axons. Both transverse and longitudinally cut particles were readily distinguished from microtubules and synaptic vesicles, thus there appears to be no relationship between tubulofilamentous particles, and microtubules or synaptic vesicles.     

Partial copurification of scrapie-associated fibrils and scrapie infectivity

The association between scrapie infectivity and scrapie-associated fibrils (SAF) during a partial purification procedure for infectivity was investigated. Scrapie infectivity and SAF can be separated from most membrane components by subcellular fractionation of infected mouse brain to obtain a synaptosomal fraction, followed by detergent treatment and density gradient centrifugation. After different detergent treatments, with either octyl glucoside or sodium N-lauroyl sarcosinate, SAF showed differing sedimentation characteristics but nevertheless cosedimented with scrapie infectivity in both cases. Copurification under two different conditions provides more evidence that SAF may be a form of the infectious agent of scrapie.     

Chronic pain states: their relationship to impairment and disability.

Chronic pain patients (101) were assigned ratings of impairment and disability and were assessed for organic pathology and pain behavior through comprehensive testing procedures. As predicted, higher ratings of impairment and disability were significantly associated with higher levels of both physical pathology and pain behaviors. These results indicate that conditioning and pathologic processes significantly influence impairment and disability ratings. Many patients showed higher disability than impairment ratings, which suggests the possibility of gainful employment in less demanding jobs. However, the current disability system rewards sickness and dysfunction and discourages patients from resuming work.     

Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever

The antigenic relatedness of surface-exposed portions of M protein molecules derived from group A streptococcal isolates representing more than 50 distinct serotypes was examined. The data indicate that the majority of serotypes fall into two major classes. Class I M protein molecules share a surface-exposed, antigenic domain comprising the C repeat region defined for M6 protein. The C repeat region of M6 protein is located adjacent to the COOH-terminal side of the pepsin-susceptible site. In contrast, Class I M proteins display considerably less antigenic relatedness to the B repeat region of M6 protein, which lies immediately NH2-terminal to the pepsin site. Surface-exposed portions of Class II M proteins lack antigenic epitopes that define the Class I molecules. Studies in the 1970s demonstrated that M protein serotypes can be divided into two groups based on both immunoreactivity directed to an unknown surface antigen (termed M-associated protein) and production of serum opacity factor. These two groups closely parallel our current definition of Class I and Class II serotypes. Both classes retain the antiphagocytic property characteristic of M protein, and Class II M proteins share some immunodeterminants with Class I M proteins, although the shared determinants do not appear to be exposed on the streptococcal surface. Nearly all streptococcal serotypes associated with outbreaks of acute rheumatic fever express M protein of a Class I serotype. Thus, the surface-exposed, conserved C repeat domain of Class I serotypes may be a virulence determinant for rheumatic fever.     

Cigar and marijuana use: their relationship in teens.

There is evidence of a substantial increase in teen use of both cigars and marijuana over the last decade. The theoretical concept of sensation seeking suggests a conceptual relationship between teen use of the substances. The hypothesis was that a relationship existed between the use of cigars and marijuana. Data for this study were gathered during the evaluation in a local school district of a teen tobacco-use reduction program. Questionnaire data and focus group results supported the study hypothesis and provided the direction for peer tobacco education to include an emphasis on this significant relationship. Identified associations between use of different substances supplies cues for the school nurse and other health providers to pursue specific areas of substance use practices when assessing students.     

Disabled counselors: perception of their effectiveness in a therapeutic relationship.

It has not been delineated how a disabled person is viewed when interacting with another person. The present study investigated subject perception of a counselor in a wheelchair who was seen in a video-taped counseling interview. Subject degree of body satisfaction was measured to assess the importance of this variable in the perception. Evaluation of the counselor was by the Barett-Lennard Relationship Inventory that measures four dimensions of a relationship: emphatic understanding, positive regard, unconditional regard and congruence. Results suggest that a counselor in a wheelchair is perceived more favorably than an able-bodied counselor along three of these dimensions and female subjects perceive him more favorably than male subjects do. Degree of body satisfaction does not seem to be a factor in this perception.     

Evidence for nonspecific adsorption of targeted retrovirus vector particles to cells

The ability to specifically target a cell-type is important for the development of vectors for in vivo gene therapy. In order to produce retrovirus vectors targeting ovarian cancer cells, which specifically overexpress alpha folate receptor (alphaFR), a single chain antibody was fused as an N-terminal extension of the ecotropic and amphotropic murine leukemia virus (MLV) envelope glycoproteins. Vector particles bearing the modified glycoproteins were produced and analysed. Although conventional FACS studies indicated that viral particles bearing the modified Env could bind to ovarian cancer cells, targeted infection was not achieved. The initial step of virus-cell interaction was further studied using an immunofluorescence technique, which allows visualisation of single retrovirus particles. Vectors bearing chimeric or wild-type glycoproteins bound equally well to cells with or without the targeted receptor, although soluble chimeric glycoproteins bound specifically to FBP. Our results indicate that the incorporation of specific ligands to the virus envelope does not necessarily result in significant enhancement of vector particle binding. A similar interaction was also observed using Env-defective virus particles, suggesting that cellular factors incorporated into the lipid envelope play a dominant role in promoting initial adsorption of virus particles to cells. Significant implications arise from these observations on the interpretation of previous reports on 'targeted' vectors, and for the development of vectors for in vivo gene therapy protocols.     

Anxiety disorders: differential diagnosis and their relationship to chronic pain

Anxiety disorders are the most prevalent type of mental disorder, and they frequently co-occur with various medical conditions, including chronic pain. Anxiety disorders are associated with higher health care costs, and comorbid chronic pain and anxiety disorder leads to worse outcomes. Despite their prevalence, anxiety disorders often go unrecognized in pain care facilities, compromising clinical benefit of pain treatment. Differential diagnosis among the anxiety disorders can be very difficult, and the high comorbidity with mood disorders, unexplained physical symptoms, and medical disorder makes the precise assessment complicated. Nevertheless, a better understanding of the research and theory that has accumulated can help clinicians accurately diagnose, conceptualize, and treat the patient's symptomatology. In this paper, the authors provide comprehensive review of the diagnostic criteria, epidemiology, differential diagnosis, and relation to chronic pain.     

Detection of immune complexes in acute rheumatic fever and their relationship to HLA-B5.

Employing five radioimmunoassays for immune complexes, the sera of 45 acute and 27 postacute follow-up sera from patients with acute rheumatic fever were examined. All patients experienced actue polyarthritis. Complexes were detected in 89% of acute-phase sera by one assay, 51% by two, 29% by three, and 7% by four. Immune complex values decreased significantly at followup, although some abnormalities persisted. There was no correlation between extra-articular manifestations and the occurrence of circulating immune complexes. Those positive for HLA-B5 demonstrated a significantly more pronounced immune response as measured by circulating immune complexes. The data indicate that circulating immune complexes occur frequently in adults with acute rheumatic fever. The relative frequency of immune complexes detected by multiple techniques in B5-positive, compared with B5-negative, patients suggests a genetic basis for the development of immune complexes in these patiemts.     

Reactions to diabetes and their relationship to time orientation

The purpose of this study was to explore the relationships between psychosocial adaptation to chronic illness and time orientation among the individuals diagnosed with insulin-dependent diabetes mellitus. Participants (N=106) were recruited via an on-line survey and an on-site health fair. Data were obtained from responses to the Reactions to Impairment and Disability Inventory and the Zimbardo Time Perspective Inventory. A series of hierarchical multiple regression analyses were performed to examine the influence of demographic- and disability-related variables, followed by a set of five time-perspective scales, on a series of psychosocial reactions to disability (anxiety, depression, anger, denial and adjustment). Findings indicated that reactions of anxiety, depression and anger were best predicted by negative perceptions of the past, whereas reactions of depression and anger also were predicted by negative views of the present. In addition, anger was associated with a decreased future orientation. Denial was best predicted by fatalistic perception of the present and, to a lesser extent, by restricted view of the future. Finally, adjustment was best predicted by positive perceptions of the present, by an expanded view of the future and by avoiding a negative view of the present. Challenging negative perceptions of the past and present, whereas facilitating a future time orientation, could be beneficial in helping clients to cope successfully with their medical conditions.     

Sleep disturbances and their relationship to glucose tolerance in pregnancy

OBJECTIVE

To explore relationships among sleep disturbances, glucose tolerance, and pregnancy outcomes.

RESEARCH DESIGN AND METHODS

Four validated sleep questionnaires were administered to 169 pregnant women at the time of 50-g oral glucose tolerance testing (OGTT) during the second trimester. Pregnancy outcomes were analyzed in 108 women with normal glucose tolerance (NGT).

RESULTS

Of the participants, 41% had excessive daytime sleepiness (Epworth Sleepiness Scale [ESS] >8); 64% had poor sleep quality; 25% snored frequently; 29% had increased risk of sleep-disordered breathing (SDB); 52% experienced short sleep (SS); 19% had both increased SDB risk and SS (SDB/SS); and 14% had daytime dysfunction. Reported sleep duration inversely correlated with glucose values from 50-g OGTT (r = −0.21, P < 0.01). Each hour of reduced sleep time was associated with a 4% increase in glucose levels. Increased likelihood of gestational diabetes mellitus (GDM) was found in subjects with increased SDB risk (odds ratio 3.0 [95% CI 1.2–7.4]), SS (2.4 [1.0–5.9]), SDB/SS (3.4 [1.3–8.7]), and frequent snoring (3.4 [1.3–8.8], after adjustment for BMI). Among NGT subjects, preterm delivery was more frequent in those with increased ESS (P = 0.02), poor sleep quality (P = 0.02), and SS (P = 0.03). Neonatal intensive care unit admissions were associated with increased ESS (P = 0.03), SDB/SS (P = 0.03), and daytime dysfunction (P < 0.01) in mothers.

CONCLUSIONS

Pregnant women experience significant sleep disturbances that are associated with increased risk of GDM and unfavorable pregnancy outcomes. Pregnant women with increased SDB risk, frequent snoring, and sleep duration of <7 h/night have increased risk of developing GDM.Sleep-disordered breathing (SDB) is present in 24% of men and 9% of women in the U.S. population (1) and has been linked to insulin resistance and type 2 diabetes (2–5). Recent studies reveal that SDB is present in up to 86% of patients with type 2 diabetes (6,7). SDB severity has been associated with poorer glucose control (6).Decreases in both duration and quality of sleep are common in pregnant women as a result of hormonal and physical factors (8,9). Collectively, these disorders have been termed pregnancy-associated sleep disorders by the International Classification of Sleep Disorders (10).Prospective studies show that SDB symptoms increase during pregnancy (11). SDB in pregnancy has been associated with preeclampsia, intrauterine growth retardation, and preterm delivery (12,13). A few recent studies using questionnaires that variably assess snoring, SDB symptoms, and/or sleep duration report an association between short sleep (SS) and/or frequent snoring and glucose intolerance and gestational diabetes mellitus (GDM) (14–16).We used four validated sleep questionnaires to obtain a comprehensive evaluation of sleep duration and quality and assess associations with glucose tolerance and pregnancy outcomes.     

Microfibrils of blood platelets: their relationship to microtubules and the contractile protein

Human blood platelets were subjected to osmotic shock, brief sonication, pressure homogenization, or treatment with adenosine diphosphate (ADP). These procedures demonstrated an abundance of cytoplasmic microfibrils. The fibrils resembled those found on electron microscopy of partially purified thrombosthenin, the actomyosin-like protein isolated from platelets, and they also appeared to resemble the myofilaments of smooth muscle. Similar fibrils were not found in leukocytes studied under identical conditions. Treatment with colchicine (2 x 10(-5) mole/liter) resulted in the disappearance of microtubules but did not affect the morphology of the microfibrils or interfere with platelet-dependent clot retraction. Thus, microfibrils rather than microtubules may represent the morphologic counterpart of the contractile protein. Brief osmotic shock at low temperature or treatment with 10(-4) M ADP caused the marginal band of microtubules to be replaced by a bundle of intertwining microfibrils. The apparent inter-conversion of microtubules and microfibrils under a variety of conditions led to the hypothesis that fibrils and tubules consist of similar subunits whose degree of polymerization might be dependent on local cytoplasmic forces. Furthermore, on the basis of these observations, it is postulated that the contractile properties of the cells may be vested in the microfibrils, whereas the tubules may serve to maintain the highly asymmetric shape characteristic of circulating and irreversibly aggregated platelets.     

Methadone concentrations in plasma and their relationship to drug dosage

We have developed a sensitive HPLC method for measuring methadone in plasma and have used it to establish that there is a linear relationship between plasma concentration and methadone dose over the range of 3-100 mg of methadone per day in a group of 31 addicts. We found a good correlation between dose and plasma concentration (r = 0.89), with the plasma methadone concentration increasing by 0.263 mg/L for every milligram of methadone consumed per kilogram of body weight. Five patients had unexpected high or low concentrations; this finding is discussed.