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E Schaeffer

Publications and source records attributed to E Schaeffer.

51 records · Page 3Linked to original sources

Characterization of a pre-S polypeptide on the surfaces of infectious avian hepadnavirus particles.

DNA from the pre-S region of the duck hepatitis B virus (DHBV) genome was inserted into an open reading frame vector designed to give high-level expression in Escherichia coli. The resulting fusion protein contained the first 8 amino acids of beta-galactosidase, 86 amino acids of the DHBV pre-S region, and 219 amino acids of chloramphenicol acetyltransferase at the C terminus (beta-gal:pre-S:CAT). Rabbit antiserum against purified beta-gal:pre-S:CAT was used to identify pre-S-containing polypeptides in DHBV particles by Western blotting. A dominant species of 36 kilodaltons (kDa) was identified. Antiserum against the major 17-kDa DHBsAg polypeptide also reacted with the 36-kDa protein. This suggests that the DHBV envelope gene polypeptides share the same carboxyl terminus, but differ in the sites from which translation is initiated. N-linked carbohydrate was not detected on either the 17- or 36-kDa envelope proteins. Anti-beta-gal:pre-S:CAT abolished infectivity of the virus in an in vitro assay. Thus, the pre-S region is exposed on the surfaces of infectious virions and may be directly involved in binding of virus to host-cell receptors.

Antibodies, Viral↗

Identification and localization of pre-s-encoded polypeptides from woodchuck and ground squirrel hepatitis viruses.

A segment from the pre-s region of the woodchuck hepatitis virus (WHV) was inserted into an open reading frame vector allowing for the expression in Escherichia coli of viral determinants as part of a fusion protein. The bacterially synthesized fusion molecule contained eight amino acids from beta-galactosidase (beta-gal) at the N terminus, followed by 89 pre-s-encoded amino acids and 219 amino acids of chloramphenicol acetyltransferase (CAT) at the C terminus (beta-gal:pre-s:CAT). This tribrid protein was used to generate antiserum which had a significant titer to the viral portion of the fusion polypeptide. Anti-beta-gal:pre-s:CAT was used in Western blot analysis to identify viral proteins containing pre-s-encoded determinants. Antiserum to the tribrid molecule recognized four WHV polypeptides with molecular masses of 33, 36, 45, and 47 kilodaltons, each of which was also recognized by a monoclonal antibody to WHV surface antigen. Using the same anti-tribrid serum, we also identified analogous polypeptides from ground squirrel hepatitis virus. The antiserum was also used to immunoprecipitate virus particles containing endogenous DNA polymerase activity, indicating that pre-s determinants are found on the surface of mature virions. Based on previous computer studies and the location of pre-s-encoded molecules on the surface of virus particles, a role in hepadnavirus host cell entry is suggested for these polypeptides.

Animals↗

Organization of the human transferrin gene: direct evidence that it originated by gene duplication.

We present the characterization of two overlapping human transferrin genomic clones isolated from a liver DNA library. The two clones represent a total length of 24 kilobase pairs and code for 70% of the protein. The organization of this gene region was elucidated by restriction mapping and DNA sequencing. It contains 12 exons, ranging from 33 to 181 base pairs, separated by introns of 0.7-4.9 kilobase pairs. This gene can be divided into two unequal parts corresponding to the known domains of the protein. Each part is essentially composed of an equal number of exons; introns interrupt the coding sequences, creating homologous exons of similar size in each moiety. Moreover, the pattern of intron interruption of the codon sequence is identical for all the analyzed homologous exon pairs. Comparison with the organization of the ovotransferrin gene shows an identical exon size distribution. These data confirm, at the gene level, the hypothesis that transferrins originated by a gene-duplication event. A model accounting for the origin of the human transferrin gene is presented.

Amino Acid Sequence↗

Pathology of chronic polychlorinated biphenyl (PCB) feeding in rats.

The hepatocarcinogenic effect of Clophen A 30 and Clophen A 60 was tested in male weanling rats by long-term feeding over a period of 832 days. The mortality rate was investigated in 100-day intervals. In the first 800 days liver carcinoma accounted for 21% of necropsies in the Clophen A 60 group but only 2% of the necropsies in the Clophen A 30 group and none in the control animals. The tumors were first observed after 700 days. After 800 days hepatocellular carcinoma was the most common lesion observed in the Clophen A 60 animals (61%) whereas it was only observed in 3% of animals in the Clophen A 30 group and 2% in the controls. Preneoplastic lesions, such as foci of hepatocellular alterations and neoplastic nodules, were first observed after Day 500. The incidence of foci predominated in all time intervals, but an increase in neoplastic nodules and hepatocellular carcinomas was observed with increased time. There was a marked trend from foci to neoplastic nodule to hepatocellular carcinoma with time. The total mortality rate and the incidence of thymoma, inflammatory lesions of the urogenital tract, in the experiment were significantly reduced by Clophen administration. Whether this protective effect could be induced by polychlorinated biphenyls (PCBs) is discussed.

Administration, Oral↗

Predicted secondary structure similarity in the absence of primary amino acid sequence homology: hepatitis B virus open reading frames.

Proteins that are related evolutionarily may have diverged at the level of primary amino acid sequence while maintaining similar secondary structures. Computer analysis has been used to compare the open reading frames of the hepatitis B virus to those of the woodchuck hepatitis virus at the level of amino acid sequence, and to predict the relative hydrophilic character and the secondary structure of putative polypeptides. Similarity is seen at the levels of relative hydrophilicity and secondary structure, in the absence of sequence homology. These data reinforce the proposal that these open reading frames encode viral proteins. Computer analysis of this type can be more generally used to establish structural similarities between proteins that do not share obvious sequence homology as well as to assess whether an open reading frame is fortuitous or codes for a protein.

Amino Acid Sequence↗

[Clinical assessment of schizophrenic syndromes (CASS): rationale, construction, reliability and sensitivity evaluation, and an attempt at normalization of the new diagnostic tool].

UNLABELLED: The CASS (Clinical Assessment of Schizophrenic Syndromes) is a new multi-purpose and multi-level clinical diagnostic instrument consisting of a diagnostic questionnaire (CASS-D) allowing for analysis of a diagnosis of schizophrenia according to DSM-IV and ICD-10 criteria, as well as of three rating scales designed for description and intensity evaluation of schizophrenic syndromes on the global (CASS-G), dimensional (CASS-P, a profile of 13 basic dimensions) or symptomatological (CASS-S, a set of 31 symptoms) level. AIM: The paper presents a rationale and construction principles of the tool followed by a study of its reliability and sensitivity as well as by preliminary attempt to normalize its results. SUBJECTS: Twelve trained diagnosticians assessed twice (at the start and end of their hospitalization) 194 inpatients admitted consecutively, within approximately 6 months, to the Department. METHOD: Results of the CASS were compared with results of the SANS/SAPS, BPRS, and PANSS assessments playing the role of standard, reference instruments. FINDINGS: High agreement coefficients (kappa) were calculated between a diagnosis of schizophrenia based on unoperationalized (clinical) criteria and operationalized diagnoses based on the CASS diagnostic questionnaire including ICD-10 and DSM-IV diagnostic criteria and algorithms. In the case of both complex (many-item) CASS scales (CASS-P, CASS-S) high reliability measures (internal consistency according to Cronbach's alpha) were found. Characteristics of frequency, intensity and dynamics of the CASS individual symptoms, dimensions and of syndrome as a whole were consistent with expectations based on clinical experience. Direct indices of clinical improvement calculated from CASS-G, CASS-P or CASS-S scores obtained at two time-points (admission, discharge) correlated fairly highly with more direct measures based on diagnosticians' clinical global impressions made when summing the results of treatment at discharge from the hospital. This finding suggests that CASS scores may sensitively register changes in patients' mental state during hospital stay and treatment. On the base of empirical distributions of CASS scales, a normalization (sten-scales) was proposed which may be useful for comparison of results obtained in differing groups of patients. Analysis of percentile and sten distributions of the CASS-P and CASS-S pointed out that patients with a diagnosis of schizophrenia had higher mean scores than patients with other diagnoses. This observation as well as above mentioned reasonableness (consistency with clinical experience) of a picture and dynamics of schizophrenic syndromes revealed in CASS assessments may be treated as preliminary assumptions of its content validity. CONCLUSIONS: Results of the study suggest that CASS has satisfactory measures of reliability and sensitiveness. They allow for a preliminary normalization of its scales and prompt to study its validity.

Humans↗

[Clinical assessment of schizophrenic syndrome (CASS): validity evaluation of the new diagnostic tool].

AIM: The aim of the study was an evaluation of validity measures of the CASS (Clinical Assessment of Schizophrenic Syndromes)--a new multi-purpose and multi-level clinical diagnostic instrument consisting of a diagnostic questionnaire (CASS-D) allowing to analyze a diagnosis of schizophrenia according to DSM-IV and ICD-10 criteria as well as of three rating scales designed for description and intensity evaluation of schizophrenic syndromes on the global (CASS-G), dimensional (CASS-P, a profile of 13 basic dimensions) or symptomatological (CASS-S, a set of 31 symptoms) level. SUBJECTS: 194 inpatients consecutively admitted to the Department within approximately 6 months were assessed twice (at the start and end of their hospitalization) by 12 trained diagnosticians. METHOD: Several measures of validity were analyzed. Results obtained by means of CASS were compared with results of the SANS/SAPS, BPRS, and PANSS as reference rating scales (diagnostic validity). Characteristics of frequency, intensity, dynamics and specificity of scale items were used to analyze content validity. Factorial structure of CASS scales was applied as a measure of construct validity. FINDINGS: Diagnostic validity of the new instrument seems to be confirmed by its very high correlation coefficients with rating scales recognized as international standards: BPRS, PANSS, and SANS/SAPS. Reasonable characteristics of frequency, intensity, dynamics and specificity of individual items (dimensions, symptoms) and sum scores of CASS scales and relationships between their values strongly suggest their content validity. Both sum (CASS-P, CASS-S) and global (CASS-G) scores of scales under study revealed some specificity--they had significantly higher values in patients with schizophrenia than in patients with other diagnoses. It allows to distinguish in a schizophrenic syndrome described by CASS components which are specific and not specific for this disorder. The latter have been left also in the final version for their practical and clinical importance. Construct validity of the CASS was studied separately for different scales (CASS-P, CASS-S) and different groups (all or only schizophrenic patients) by means of several factor analyses, and performed along identical statistical procedure (principal component method of extraction with criterion eigenvalue > 1, followed by Equamax rotation). Resulting solutions could be interpreted reasonably and consistently with contemporary attempts to find adequate factorial models of intrinsic structure of schizophrenic syndrome. Thus they support confidence for constructive aspect of the CASS validity. CONCLUSIONS: Ultimately, results obtained in the study suggest that the CASS may be considered as an instrument with some promising indices of diagnostic, content and construct validity, which may be potentially useful for clinical and research purposes.

Humans↗

[Assessment and self-assessment of patients' attitudes toward their psychotic disorders].

The aim of the study was the evaluation of concordance between rating and self-rating of attitudes toward psychotic disorders in one hundred patients (72 of them with diagnosis of schizophrenia). At discharge from the hospital patients were examined by two scales: Experience of Illness Scale (for rating) and My Experience of Illness Scale (for self-rating). Moderate concordance of results of rating and self-rating of the overall patients' attitude was noted. The higher concordance was found on dimension of evaluation of the illness experience, lower on dimension of reflectiveness to disease experience, and the lowest one on dimension of identification of the disease with self. Two different scales, simultaneously used, seem very beneficial because they reflected attitudes from two different perspectives, creating more complete a picture.

Adolescent↗

[Psychopathological profile of acute schizophrenic syndromes diagnosed according to ICD-10 and DSM-IV criteria].

Diagnostic and symptomatological profiles of schizophrenic syndromes diagnosed according to ICD-10 and DSM-IV were compared. For this reason a group of patients fulfilling at least one of these sets of criteria was created and then diagnostic and symptomatological profile was compared between those who fulfilled the ICD-10 and those who fulfilled DSM-IV criteria. 105 inpatients hospitalized in acute phase of their first or one of consecutive episodes were included--102 of them had fulfilled ICD-10, and 90 DSM-IV criteria of schizophrenia. Diagnostic concordance between the two systems of criteria was high (83%). Differentiation of diagnostic profile (i.e. difference between frequency of fulfilling the specific requirements of ICD-10 or DSM-IV criteria) of the symptoms in these two groups was not significant, expert of 6-month criterion of duration of illness, which was significantly less frequently valid in ICD-10 syndromes group. A comparison of symptomatological profiles (i.e. frequency and intensity of symptoms) of schizophrenic syndromes diagnosed by ICD-10 or DSM-IV criteria and described by several rating scales (PANSS, SAPS/SANS, KOSS-S) did not show any significant differences. Results suggested that despite of different ways of defining the schizophrenic syndromes in both diagnostic systems, disorders manifested in the groups of patients created by means of them are very similar in psychopathological picture. This seems to be a significant change in comparison to more prominent differences contrasting the previous versions of the diagnostic systems (i.e. ICD-9 and DSM-III-R).

Acute Disease↗