Diversity of envelope antigens on murine type-C RNA viruses.
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Biomedical subjects
Publications and source records attributed to M Liu.
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By inhibiting techniques using indirect immunofluorescence tests and indirect immunoelectron microscopy, the G(Gross) soluble antigens (GSA) in the body fluids of AKR and C58 mice, which have a high incidence of spontaneous leukemia, were classified according to the known specificity of G antigens in the murine Gross leukemia system. GSA existing in the plasma of nonleukemic and leukemic AKR mice and in the ascitic fluid of transplanted AKR spontaneous leukemia K36 showed the several specificities corresponding to G cell surface antigens, GCSAa, b, and c, and type-specific and group-specific viral envelope antigens, tsVEA and gsVEA, respectively. However, the plasma of nonleukemic C58 mice lacks GSAc, which can be recognized by the G-typing mouse serum. GSA corresponding to G(IX) antigen was not detected in the body fluids.
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Missing data in clinical trials are inevitable. We highlight the ICH guidelines and CPMP points to consider on missing data. Specifically, we outline how we should consider missing data issues when designing, planning and conducting studies to minimize missing data impact. We also go beyond the coverage of the above two documents, provide a more detailed review of the basic concepts of missing data and frequently used terminologies, and examples of the typical missing data mechanism, and discuss technical details and literature for several frequently used statistical methods and associated software. Finally, we provide a case study where the principles outlined in this paper are applied to one clinical program at protocol design, data analysis plan and other stages of a clinical trial.
To determine whether large and repeatable c-waves can be recorded from rabbits with equipment already in use in clinical electroretinographic laboratories, the Burian-Allen electrode, connected bipolarly or monopolarly, was used to record electroretinograms from pigmented rabbits. The Jet electrode was also used. The c-waves elicited by long-duration (4-second) stimuli were compared to those elicited by stroboscopic stimuli. In addition, the c-waves recorded with direct-coupled amplification were compared to those recorded with condenser-coupled amplification (one-half-amplitude bandpass=0.1 Hz). The b-wave amplitude was not altered by the amplifier coupling or by the two stimulus durations. The largest c-waves were elicited by 4-second-duration stimuli and recorded with direct-coupled amplification. Although the c-wave amplitude was reduced by stroboscopic stimuli and by condenser coupling, large and repeatable c-waves were elicited by stroboscopic stimuli and recorded with condenser-coupled amplification. A comparison of stimulus duration and amplifier coupling showed that the stimulus duration was more important in recording large-amplitude c-waves. Similar results were obtained with the Jet electrode. We conclude that repeatable and large c-waves can be elicited by a stroboscopic stimuli and can be recorded with condenser-coupled amplification with good low-frequency response from rabbits.
Previous studies have shown that adenosine agonists acting at A-2 receptors inhibit platelet aggregation. Since an increase in cytosolic Ca2+ concentration (delta [Ca2+]i) is closely associated with the time frame of platelet aggregation, we have examined the effect of adenosine receptor function on induced increases of [Ca2+]i by a potent platelet activator, platelet activating factor (PAF). We loaded washed platelets with Fura-2, then induced increases in [Ca2+]i with various concentrations of PAF, and then determined EC50 values (PAF concentration at half-maximal response) and values for maximal response of delta[Ca2+]i (max-delta[Ca2+]i). The EC50 for PAF-delta[Ca2+]i was 112 +/- 37 (SD) pM and the max-delta[Ca2+]i was 284 +/- 138 (SD) nM. Our results show that PAF-delta[Ca2+]i was inhibited in a non-competitive manner by the adenosine receptor agonist cyclohexyladenosine (CHA) with an IC50 of 14.9 microM. This inhibition was partially reversed by theophylline, an adenosine receptor antagonist, with an IC50 of 19 microM. Based on the results of these studies together with evidence from other research groups that platelets do not possess A-1 receptors, our results suggest that CHA inhibited PAF-delta[Ca2+]i in platelets through an activation of A-2 receptors.
Positive EEG deflections with the latency and scalp distribution of the P300 accompany startle in response to loud auditory stimuli in a non-task context. The purpose of this investigation is to determine if habituation would have effects on the P300 similar to those on the startle blink. Thirty-four normal 7 to 11-year-old boys from a startle habituation study had EEG recordings of sufficient quality to provide data for the current study. Startle was measured both as orbicularis oculi EMG and vertical EOG and P300 was recorded at Pz in response to 40,104 dB bursts of white noise presented at 23-s intervals. Both the startle response and the P300 habituated toward asymptotic levels after the first 28 trials, suggesting that both startle and the subsequent cognitive evaluation of the startling stimulus, reflected in the P300 response, are modulated by a common neurophysiological mechanism extrinsic to the direct startle pathway. A modest significant correlation between the P300 and the vertical EOG peak latencies for the initial trials suggests that the cognitive evaluation of the startling stimulus may also include evaluation of the reflex response to that stimulus. Analyses of the within-subject associations between startle and P300 initial amplitudes and rates of habituation showed that these parameters varied independently within the individual subject, suggesting that the P300 is not a component of the startle response. Rather, it reflects an evaluation of the startling stimulus, decreasing in amplitude as the surprising value of the startling stimulus decreases with habituation.
A 33-year-old man with a history of intravenous drug abuse was seen with fever, septic pulmonary embolization, and Staphylococcus aureus bacteremia. Transthoracic echocardiography was nondiagnostic. Transesophageal echocardiography showed a large, pedunculated, and highly mobile vegetation attached to the eustachian valve.
The extracellular matrix between cardiocytes has been suggested to play an important role in maintaining the structure and function of the heart. The purpose of this study was to elucidate the morphological changes in the collagen of the extracellular matrix (ECM) in the hearts of pigs with hypertrophic cardiomyopathy. Sixty pigs diagnosed with hypertrophic cardiomyopathy from 605 purebred Landrace pigs ages 6 to 9 months were used in this study. Morphologically, these pigs with hypertrophic cardiomyopathy had increased heart weight and heart-to-body weight ratio, thickening of the left ventricular (LV) and right ventricular (RV) free walls and septum, disorientation of cardiocytes, myocardial fibrosis, and intramural coronary arteriosclerosis. Similar observations have been described in our preliminary report (Cardiovasc Pathol 3:261, 1994). In the present study, we have modified the silver impregnation technique to stain paraffin-embedded sections to demonstrate three types of ECM. There were endomysial struts, perimysial weaves, and epimysial coils in the myocardium. The light microscopic findings of the struts, weaves, and coils were also confirmed by scanning electromicroscopic examination. The numbers of these fine structures were increased significantly in the pigs with hypertrophic cardiomyopathy. In addition, the amounts of collagen in the LVs, RVs, and septum (Sep) in pigs with hypertrophic cardiomyopathy (LV = 19.37+/-0.79, RV = 23.72+/-0.72, Sep = 20.38+/-0.94 microg/mg, n = 60) were significantly higher (p < 0.01) than that in similar areas of normal pigs (LV = 14.56+/-1.11, RV = 18.90+/-1.02, Sep = 14.99+/-1.33 microg/mg, n = 30, respectively). Our findings of an overall increase of collagen content suggested that the accumulation of collagen matrix might be another factor responsible for the diastolic dysfunction of hypertrophic cardiomyopathy. These results might also infer that the increased collagen matrix could contribute to the stiffness of the cardiac chambers, thereby markedly affecting systolic and diastolic function of the heart. These observations provide further support that the pig may be an animal model for human cardiovascular disease.
A region of dorsomedial frontal cortex (DMFC) has been implicated in planning and executing saccadic eye movements; hence it has been referred to as a supplementary eye field (SEF). Recently, activity related to executing smooth-pursuit eye movements has been recorded from the DMFC, and microstimulation here has been shown to evoke smooth eye movements. This report documents neuronal activity present in smooth-pursuit tasks where the predictability of target motion was manipulated. The activity of many neurons in the DMFC reached a peak when a predictable change in target motion occurred. Furthermore, the peak activity of some cells was systematically shifted by manipulating the duration of the target event, indicating that the network these neurons were in could learn the temporal characteristics of new target motion. Finally, the activity of most neurons tested was greater when target motion was predictable than when it was unpredictable. The results suggest that the DMFC participates in planning smooth-pursuit eye movements based on past stimulus history.
Polyether dendritic compounds bearing folate residues on their surface were prepared as model drug carriers with potential tumor cell specificity. Starting from ester-terminated polyether dendrimers, hydrazide groups were easily introduced to the surface of the dendrimers by reaction with hydrazine. Folate residues were then conjugated to the hydrazide chain ends of the dendrimers by direct condensation with folic acid in the presence of a condensing agent or by reaction with an active ester derivative of folic acid. Essentially complete functionalization of the terminal hydrazide groups was achieved for both the first and the second generation dendrimers with four and eight hydrazide groups. For the G-2 dendrimer with 16 hydrazide groups, an average number of only 12.6 folate residues were attached to each dendrimer. The conjugates are soluble in aqueous medium above pH 7.4. In addition, a similar conjugation of the antitumor drug methotrexate to the dendrimer was also investigated. Once optimized, these molecules may form the basis for a novel family of multivalent drug carriers.
The difficulty patterns of FIM (Functional Independence Measure) in Japan were determined and compared with patterns found in the United States to assess whether FIM can be used for worldwide comparisons of ADL (the activities of daily living). The FIM was measured for 190 stroke patients in several hospitals throughout Japan. The scores at admission and discharge were converted to an interval scale by Rasch analysis. Right and left brain lesion patients were analyzed separately. The FIM items were divided into two groups: motor items and cognitive items to minimize misfit. A degree of misfit was acceptable, except for bowel and bladder management, stairs, bathing, and expression. Motor items, eating, and bowel and bladder management were the easiest; stairs, bathing, and tub/shower transfers were the most difficult. The difficulty patterns of patients with left and right hemisphere lesions were almost identical. Bathing and tub/shower transfer were more difficult for Japanese patients than for those studied in the United States. Concerning the cognitive items, expression was easiest for patients with right hemisphere lesions but most difficult for those with left hemisphere lesions. Social interaction was easier for Japanese patients with left hemisphere lesions than the other patients. The item difficulty patterns in Japan differs slightly from those in the United States because of cultural differences. As countries show different patterns of difficulty, we must be careful when making international comparisons of FIM data converted by Rasch analysis.
The Functional Independence Measure for Children (WeeFIM) was developed based on the FIMSM instrument to assess disability in children aged six months to seven years. Its reliability and validity have been studied, and normative data are available for American children. The WeeFIM instrument is potentially an internationally useful instrument, but data from other countries are lacking. The objectives of this study are to examine whether the WeeFIM instrument is applicable to Japanese children and to describe preliminary normative data. To study interrater reliability, we had two examiners assess 20 nondisabled children and calculated weighted kappas for individual item scores and intraclass correlation coefficients for total scores and motor and cognitive subscores. We then assessed 110 nondisabled children ages six months to seven years to obtain normative data and compared them with the American data. In 51 of these healthy children, we compared total WeeFIM scores with developmental ages as obtained with the Tsumori test, a standardized developmental test widely used in Japan to assess its concurrent validity. The weighted kappas were greater than 0.8, and the intraclass correlation coefficients were greater than 0.98. Total scores and motor and cognitive subscores increased with age, reaching a plateau at 60 to 72 months, which is similar to the American data. There were three patterns of chronologic changes in individual item scores: items showing high correlations with age (Spearman's rho > 0.8; grooming, dressing, memory, etc.), moderate correlations (0.8 > rho > 0.7; eating, bladder, comprehension, etc.), and lower correlations (0.7 > rho > 0.6; locomotion and chair transfer). Total scores correlated significantly with developmental ages (Spearman's rho = 0.938), but there was a discrepancy between each item score and the pass-or-fail patterns of the Tsumori test. This study demonstrated the applicability of the WeeFIM instrument to Japanese children with satisfactory reliability and validity and provided preliminary normative data for future studies.