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Biomedical subjects

M Philipp

Publications and source records attributed to M Philipp.

At least 73 records · Page 4Linked to original sources

Can the scanning tunneling microscope sequence DNA?

A revolutionary new microscope, the scanning tunneling microscope (STM), can image some surfaces at atomic resolution, even in air or water. It can produce high-resolution images of DNA, and we outline what we know of its mechanism, concluding that it may be able to sequence DNA. This application would require major advances in sample preparation in order for the technique to compete with conventional methods. On the other hand, the STM may provide a very useful alternative to gels for probing sequence-directed structural features.

Base Sequence↗

Animal models in the study of the phenomenon of parasitism: filariae and other parasites.

The Round table has emphasized the absolute necessity of in vivo research showing the complexity of host reaction to the parasite. The results obtained in vitro can only provide a preliminary indication, because any interference with the culture is susceptible of changing the precarious balance of the parasite in that artificial environment. The subject proposed here cannot be treated wholly, but some particular topics could be discussed: 1--searching for appropriate models; 2--parasite strains; 3--some aspects on pathology and drug development; 4--vaccines; what significance in a natural host-parasite relationship can be gathered from a non-natural one?

Animals↗

Anti-idiotypic antibodies function as a surrogate surface epitope of Brugia malayi infective larvae.

Anti-idiotypic (AB2) antibodies were generated in rabbits following immunization with a murine IgM monoclonal antibody (AB1) recognizing a surface determinant of Brugia malayi infective stage larvae. AB2 specifically inhibited the binding of AB1 to B. malayi larvae. Furthermore, AB2 had the ability to mimic the original antigen since mice immunized with AB2 possessed serum antibodies (AB3) specific for the B. malayi surface determinant. The presence of anti-surface antibodies (AB3 and AB1) induced either by AB2 immunization or by administration of AB1, did not alter the outcome of an intraperitoneal infection of B. malayi larvae in BABL/c mice when compared to untreated animals. AB3 antibodies like AB1, were IgM, thus indicating an isotype restricted response to the B. malayi epitope. There were no detectable cell mediated responses to the surface determinant in mice immunized with AB2, assessed by lymphocyte blastogenesis or IL3 production in vitro in response to the idiotope as presented by living larvae. The lack of cellular responses and/or the previously demonstrated rapid shedding of the epitope may explain the inability of AB1 or AB2 to protect mice against larval challenge in this study.

Animals↗

Comparison of the ICD-10-classification with the ICD-9- and the DSM-III-classification of mental disorders.

The diagnostic concepts in ICD-10 show better congruence with those in DSM-III than with those in ICD-9. The diagnostic definitions used by ICD-10 and DSM-III for the majority of diagnoses turn out to be similar; the definitions of anxiety disorders and schizoaffective disorders are, however, still at variance. Consequently, the empirical results from the WHO field trial in German-speaking countries reveal a high degree of overlap between the two systems; the degree of overlap between ICD-9 and ICD-10 was lower, but still surprisingly high overall. These empirical results support the validity of ICD-10.

Humans↗

Genes that can be mutated to unmask hidden antigenic determinants in the cuticle of the nematode Caenorhabditis elegans.

Rabbit antisera directed against a mixture of proteins solubilized from the wild-type adult Caenorhabditis elegans cuticle were used to isolate mutants, induced by ethyl methanesulfonate treatment, that exhibit alterations in surface antigenicity by immunofluorescence. Genetic mapping and complementation data for four such mutations define two genes, srf-2(I) and srf-3(IV). The mutant phenotypes observed by immunofluorescence appear to result from unmasking of antigenic determinants that are normally hidden in the wild-type cuticle. In support of this hypothesis, surface radioiodination experiments indicate that components labeled on the wild-type surface are missing or less readily labeled on the surface of srf-2 and srf-3 mutants.

Animals↗

Antigenic and dynamic properties of the surface of Onchocerca microfilariae.

We analyzed the antigenicity and stability of the surface of skin microfilariae (mf) of Onchocerca cervicalis, a horse parasite. These mf express antigens on their surface that are cross-reactive with the cattle parasite O. lienalis and with the human parasite O. volvulus. The surface of living O. cervicalis mf was radioiodinated using Iodogen and the labeled components were solubilized in buffers containing sodium dodecyl sulphate (SDS), or extracted with the milder detergent octyl-beta-D-glucopyranoside (OGP). Electrophoresis of this material showed seven prominent bands, one of which (14 kDa) was specifically precipitated by antisera from rabbits immunized with mf from either O. cervicalis, O. lienalis, or O. volvulus, and by human sera obtained from infected individuals in Chiapas, Mexico. Other components were precipitated by either the rabbit or the human sera. In addition, antisera from mice immunized with O. cervicalis mf bound specifically to the surface of freeze-thawed uterine O. lienalis and O. volvulus mf as detected by immunofluorescence. This fluorescence was lost from the surface of O. cervicalis mf in a temperature-dependent fashion. Live mf incubated on ice with mouse anti-mf antisera and secondary FITC-GAM, showed uniform surface fluorescence. When these mf were incubated at 37 degrees C, but not at 0 degrees C, the fluorescent pattern changed with time. First, small non-fluorescent patches arose, followed by an increasingly wide belt devoid of fluorescence, and finally, no visible fluorescence. These changes in the mf surface suggest potential mechanisms for immune evasion by filarial parasites.

Animals↗

A lambda gt11 cDNA recombinant that encodes Dirofilaria immitis paramyosin.

The cDNA synthesized from mRNA of Dirofilaria immitis female adult worms was cloned into the expression vector lambda gt11. Screening the library with a hyperimmune rabbit antiserum raised against adult worm homogenates yielded several antigen positive clones. One of these clones, lambda cDi2, was recognized by rabbit antisera raised against either D. immitis L-3, adult, Brugia malayi L-3 or Onchocerca volvulus adult worm antigen, as well as by antisera from humans naturally infected with O. volvulus or Wuchereria bancrofti. Affinity-purified anti-lambda cDi2 antibodies reacted with a 97-kDa protein on Western transfers of adult D. immitis antigen extracts that were reduced with beta-mercaptoethanol. The whole rabbit anti-D. immitis adult antiserum depleted of anti-lambda cDi2 antibodies exhibited decreased reactivity to this 97-kDa band. A monoclonal antibody (IA6) that specifically binds Schistosoma mansoni paramyosin also recognised a 97-kDa protein in D. immitis extracts upon Western transfer. The deduced amino acid sequence of partial DNA sequence from lambda cDi2 showed some similarity to nematode myosin, and gave a stretch of 82 amino acids that is 91.5% identical to Caenorhabditis elegans paramyosin: thus, lambda cDi2 encodes D. immitis paramyosin.

Amino Acid Sequence↗

[Chronic paranoid-hallucinatory psychosis as the initial manifestation of an HIV infection?].

In a 36-year-old patient an acute onset of psychosis occurred, probably due to HIV infection. For one year HIV-infection with reduced T4/T8 ratio had been known without clinical manifestation (stage IV B of the CDC-classification). He developed chronic delusional hallucinations, which persisted for more than one year in spite of adequate psychoactive drug therapy. So far AIDS-related dementia has not become evident. Focal lesions caused by opportunistic infections or tumour were excluded by computed tomography and magnetic resonance imaging. The latter revealed several small lesions and the brain scan showed a nonhomogeneous pattern of cerebral blood flow. CSF-examination disclosed a mild lymphocytosis and raised protein concentration. A classification as an organic, HIV-induced delusional hallucination seems to be justified.

Acquired Immunodeficiency Syndrome↗

Computed tomography in depression: association between ventricular size and psychopathology.

The relationship between psychopathology and brain alterations, measured by computed tomography (CT), was investigated in 44 depressed patients. Comparisons of ventricle-brain ratio (VBR) between "endogenous" vs. "nonendogenous" subgroups, classified by six distinct diagnostic systems, revealed no significant differences. The VBR and the width of the third ventricle correlated significantly with scores on the Brief Psychiatric Rating Scale, the Global Assessment Scale, the Bech-Rafaelsen Melancholia Scale, the Rating for Emotional Blunting, and the Scale for the Assessment of Negative Symptoms, but not with scores on the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety. Item analyses of the Bech-Rafaelsen Melancholia Scale revealed that retardation-related items were most significantly correlated with ventricular size. The wider diameter of the third ventricle in psychotic patients was associated with higher scores on retardation in the psychotic subgroup, whereas the greater distances of both Sylvian fissures showed no relationship to psychomotor retardation. No significant correlations were found between CT values and anxiety, suicidal impulses, somatic complaints, and sleep disturbances.

Adult↗

Diagnostic determinants of response to treatment with tricyclic antidepressants: a polydiagnostic approach.

In an attempt to find diagnostic predictors of treatment response, 45 inpatients with major depression in a randomized trial received amitriptyline or imipramine for 23 days after a washout period of 16 days. A polydiagnostic approach was applied to the classification of endogenous depression. Only a minority of diagnostic schedules for endogenous depression proved predictive of a more favorable course during antidepressant treatment: the criteria of D. F. Klein, the Newcastle Scale II, and the Vienna Research Criteria. The symptoms of nonreactivity of mood and diurnal variation were the only endogenous symptoms with predictive ability. In addition, psychotic features and secondary depression predicted an unfavorable course, whereas characteristics of previous course (bipolarity, recurrence) were not predictive.

Adult↗

A German validation study of the inventory to diagnose depression.

The Inventory to Diagnose Depression (IDD), a self-rating scale designed to identify major depressive episodes (MDE) according to DSM-III, was validated in a sample of 83 inpatients. Depending whether the time criterion of MDE was included or omitted, 63 or 77 patients obtained a syndrome diagnosis of MDE established by means of a structured clinical interview (Polydiagnostic Interview) which served as yardstick. Sensitivity (84.1% with time criterion, 89.6% without time criterion), specificity (60%, 50%), predictive value (67.8%, 64.2%) and kappa (0.43, 0.29) were calculated and found to necessitate improvement for a reasonable application of the IDD in epidemiological and clinical settings. Adapting the IDD algorithm to DSM-III-R diagnosis of MDE, analogous results were obtained.

Adult↗

Improving depression severity assessment--I. Reliability, internal validity and sensitivity to change of three observer depression scales.

The Hamilton Depression Scale (HAMD) is the most commonly used scale for depression severity assessment and for antidepressant treatment evaluation. Alternative scales have been proposed by Bech and Rafaelsen (BRMS) and by Montgomery and Asberg (MADRS) to try to overcome the shortcomings of HAMD: they are based on different concepts of severity and different scaling procedures. Comparisons with respect to reliability, validity and ability to detect change have been performed using these scales in different samples. The BRMS proved superior. This result makes it necessary to question the usual procedure of testing the efficacy of antidepressants by means of HAMD alone. Problems in defining the severity of depression and in testing the validity of severity scales are discussed.

Adult↗

Improving depression severity assessment--II. Content, concurrent and external validity of three observer depression scales.

The Hamilton Depression Scale (HAMD), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Bech-Rafaelsen Melancholia Scale (BRMS) were compared with respect to content, concurrent and external validity in sample of 130 patients with a major depressive episode. The three scales did equally well in concurrent and external validity. The HAMD showed some deficiencies in content validity. The consequences for depression severity assessment are discussed.

Adult↗