Aminoacylation of rat liver transfer RNA with L-penicillamine. On the specificity of the aminoacylation reaction.

L-]14C]Penicillamine is bound to RNA from rat liver in an in vitro reaction catalyzed by rat liver aminoacyl-tRNA synthetases. Addition of certain naturally occuring amino acids results in a significant decrease of L-penicillamine binding. The most potent inhibitor of this binding is L-valine, followed by L-isoleucine and L-threonine. Amino acids without structural relationship to L-penicillamine in the non-functional part of the molecule, such as L-phenylalanine, are ineffective. Studies on the competition of L-penicillamine and L-isoleucine, respectively, with L-valine demonstrate the high specificity of the aminoacylation reaction. They show that the change of L-penicillamine binding to tRNA Val is considerably lower than that of L-valine.

Overexpression of chicken interferon regulatory factor-1 (Ch-IRF-1) induces constitutive expression of MHC class I antigens but does not confer virus resistance to a permanent chicken fibroblast cell line.

The chicken fibroblast cell line C32 has been transfected with the chicken homolog (Ch-IRF-1) of the mammalian transcription factor IRF-1. Stable transfectants were generated, constitutively overexpressing Ch-IRF-1 mRNA and protein. Cells overexpressing Ch-IRF-1 showed enhanced constitutive expression of MHC class I (B-F, beta-microglobulin) antigens. With increasing number of passages cells with normal B-F IV surface antigen expression accumulated. In the revertants, the amount of Ch-IRF-1 mRNA was reduced. Overexpression of Ch-IRF-1 had no effect on the constitutive expression and the induction by chicken interferon type-I and type-II (Ch-IFN) of guanylate-binding protein (GBP). Susceptibility to vesicular stomatitis virus, sindbis virus, Newcastle disease virus and vaccinia virus was not altered by overexpression of Ch-IRF-1. An antiviral state could be induced against all viruses tested by similar amounts of Ch-IFN type I in clone 20-18 expressing Ch-IRF-1 and cells transfected with empty vector.

Altered fronto-central PINV topography and the primary negative syndrome in schizophrenia.

Postimperative negative variation (PINV) was recorded during a warned reaction time paradigm in 16 chronic DSM-IIIR schizophrenics in remission. Clinical symptoms were assessed by BPRS, SANS and the anhedonia scale of the Chapman Questionnaire. Ten healthy controls were studied in the same manner. Over the fronto-central area we found a significantly elevated PINV amplitude with an altered topographical distribution in the patient group. The difference values 'PINV Cz-PINV Fz' were correlated negatively with primary negative symptoms of schizophrenia.

Trimipramine--an atypical neuroleptic?

Trimipramine and clozapine show some similarities in their receptor binding profiles. Since both have the same affinity for the D2 receptor and since the affinity for this receptor correlates closely with the antipsychotic potency of a drug, an antipsychotic efficacy of trimipramine in acute schizophrenia could be expected. Therefore 28 schizophrenic patients in an acute phase were treated with trimipramine up to 400 mg/d in an open clinical trial. For the whole group of patients the BPRS total score changed from 58 +/- 5 before treatment to 46 +/- 18 at the last rating (p less than 0.05). According to our clinical judgement the patients were divided into three subgroups. Thirteen patients showed a good remission under trimipramine so that they could be discharged on a trimipramine maintenance treatment. They improved on the BPRS from 58 +/- 6 before treatment to 32 +/- 8 at endpoint. Six patients deteriorated during the first week of treatment and had to be withdrawn from the study. Nine patients showed insufficient improvement or became worse after an initial improvement. The observed side-effects (dry mouth, sedation, sweating, increased appetite, constipation, tremor, vertigo) are well known under trimipramine and were therefore expected. Beyond these, one patient developed a cardiac insufficiency. No clinical relevant extrapyramidal side-effects occurred. Since the improvement of florid psychotic symptoms seems to be markedly higher under trimipramine than the one reported under placebo, our results indicate that trimipramine may have an antipsychotic potency.

Evoked potential assessment of mental function during recovery from severe head injury.

Event-related potential recording and neuropsychologic testing were carried out on 18 severely head-injured patients and on a control group. At early stages of injury the patients had prolonged P3 latencies and reduced psychometric scores. In the assessment of individual patients the P3 latency proved to be a measure that diagnosed cognitive impairment with clinically acceptable levels of accurate classification. On retesting 4.6 +/- 1.6 months after trauma, normal values were found for the neuropsychologic measures and a residual latency prolongation for P3, indicating the P3 latency to be a sensitive index of subtle residual brain dysfunction due to head injury.

2',5'-Oligoadenylate synthetase activity analysis and human papilloma virus typing as prognostic factors in patients with recurrent respiratory papillomatosis.

OBJECTIVE: Determination of early prognostic factors in patients with recurrent respiratory papillomatosis is extremely important, so the major goal of our prospective, multicentre study was to evaluate (1) the feasibility of various factors to determine prognosis of the clinical course, as well as (2) the response to interferon-alpha therapy in recurrent respiratory papillomatosis. METHODS: Forty-two patients with recurrent respiratory papillomatosis were treated with interferon-alpha (3 MU/m(2) three times per week; mean therapy duration was 2.7 +/- 1.8 years) in 1983-1994 and followed-up until 2003. Human papilloma virus (HPV) type, recurrent respiratory papillomatosis severity and 2',5'-oligoadenylate synthetase activity were determined by standard methods and analysed for correlation with the results of long-term clinical outcome. RESULTS AND CONCLUSION: Patients with HPV type 11, a severity score >4, a high number of surgical procedures prior to interferon-alpha therapy and a high basal 2',5'-oligoadenylate synthetase activity should be considered at high risk of an aggressive clinical course, often with spread to lower airway passages, malignant transformation and death. Human papilloma virus type, score for recurrent respiratory papillomatosis severity, number of surgical procedures and 2',5'-oligoadenylate synthetase activity showed significant association with response to interferon-alpha therapy and the long-term clinical course, so these factors have value in predicting prognosis in recurrent respiratory papillomatosis.

[D-Penacillamine. From constituent of penicillins to significant drug]. / D-Penicillamin: Vom Baustein des Penicillins zum vielseitigen Pharmakon.

D-Penicillamine is used against a variety of diseases. For many years it has been successful in treating Wilson's disease, cystinuria and heavy-metal poisonings. It also proved to be effective against rheumatoid arthritis, scleroderma, chronic active hepatitis, pulmonary fibrosis and multiple sclerosis. However, the use of D-penicillamine is still limited owing to the frequent occurrence of considerable, though generally reversible, side effects. This article deals with the history of D-penicillamine as well as the methods of its synthesis, its pharmacokinetics, effects and side effects. In addition, the significance of the stereo isomeric L-penicillamine is discussed.

[Interferons--research, effects and importance]. / Die Interferone. Erforschung, Wirkung und Bedeutung.

Interferons are a family of proteins synthesized by the cells of higher organisms as a first reaction to viral infections, preceding the immune response. They are also involved in the regulation of the immune system and therefore included among the lymphokines. Since they had been shown to have antitumor activity in vitro and in experimental animals, they were suggested to be powerful drugs in cancer therapy.

PINV--topography and primary negative symptoms in chronic schizophrenia.

PINV was recorded during a warned reaction time paradigm in 16 chronic schizophrenics in remission. Clinical symptoms were assessed by BPRS, SANS, and the anhedonia scale of the Chapman Questionnaire. Ten healthy controls were studied in the same manner. Over the frontocentral area we found a significantly elevated PINV amplitude with an altered topographical distribution in the patient group. The difference values "PINVCz-PINVFz" were correlated negatively with primary negative symptoms of schizophrenia.

[Rehabilitation of psychiatric patients in the halfway house--a 10-year retrospective study]. / Rehabilitation psychisch Kranker im Ubergangswohnheim--Ein 10-Jahres-Rückblick.

In a period of ten years 159 residents were admitted to a transitional home. 90% of them were diagnosed as chronic schizophrenics with a marked psychic and social handicap. With an average age of 28.7 years and a mean duration of illness of 6.8 years most of the patients had been hospitalized several times; 95% had no job, lived on social assistance or were invalidity pensioners. There was poor success in vocational rehabilitation (22%). Better results were seen in solving the housing problems, showing a clear-cut tendency to move from the family of origin into protected group homes or independent living. Positive effects of social training with gains in life-coping abilities and social competence, i.e., in autonomy in everyday life could be observed as well.

Influence of anticoagulants on the determination of interferon.

The presence of anticoagulants in plasma samples can spuriously increase the titers obtained in interferon bioassays by influencing interactions between the cell and the challenge virus. These artifacts can be eliminated by washing the test cell cultures before the virus challenge is added.

[Demands and reality in the rehabilitation of psychiatric patients. Results of a follow-up study in established need for rehabilitation with reference to the housing and/or vocational sphere]. / Anspruch und Wirklichkeit der Rehabilitation psychiatrischer Patienten. Ergebnisse einer Verlaufsuntersuchung bei festgestelltem Rehabilitationsbedarf auf der Wohn- und/oder Arbeitsachse.

At an index day all 166 patients of the Department of General Psychiatry were asked whether changes of working or housing condition were considered necessary and which definite steps had to be done. In 85 (51.2%) of 166 patients changes were considered necessary. What measures had been initiated or carried out? Concerning the housing situation age and disease (psychiatric diagnosis) proved to be important factors; concerning the working situation age, sex, socioeconomic status and length of unemployment were important.

[Event-related potentials in schizophrenic patients in the acute phase and in remission]. / Ereigniskorrelierte Potentiale bei schizophrenen Patienten im akuten Krankheitsschub und in Remission.

In 15 schizophrenic patients event-related potentials were recorded during an auditory two-tone-discrimination task in the acute phase and after remission. The control group consisted of ten healthy subjects of the same age. The schizophrenic patients showed reduced amplitudes of N1, P2 and P3 and prolonged latencies of N2 and P3 independent of neuroleptic medication and clinical state. We found no differences in the topographical distribution of P3 between schizophrenic patients and controls. The changes of the event-related potentials in the schizophrenic patients may be interpreted as electrophysiological correlates of basic disturbances in information processing in schizophrenia.

Quantitative determination of small amounts of L-penicillamine in D-penicillamine after desulfurization with Raney nickel.

Commercially available D-penicillamine is desulfurized with Raney nickel at room temperature in aqueous solution. L-Valine derived from contaminating L-penicillamine is determined colorimetrically by the amino acid oxidase/peroxidase reaction, using 2,2'-azino-di-[3-ethyl-benz-thiazoline-sulfonate(6)] (ABTS). The procedure assures the quantitation of L-penicillamine contaminating D-penicillamine down to the level of 0.1%.

[Alpha interferon in the therapy of cutaneous T cell lymphomas]. / alpha-Interferon in der Therapie kutaner T-Zell-Lymphome.

5 patients suffering from T-cell lymphomas at different stages were treated with human alpha-interferone. One of the patients showed mild partial remission, two patients had but a poor and short-lasting improvement of their condition, in one case there was no change at all, and in another case, worsening of the clinical picture was observed. Controls of the relevant laboratory parameters (including NK-cells, T-cell subpopulations, antibodies and complement, oligo-(A)-synthetase, and interferone serum levels) did not always reveal the changes that had been expected to be induced by the therapy.

[Serum interferon level and (2'-5')-oligo(A) synthetase activity in pityriasis rosea, basalioma, melanoma and molluscum contagiosum]. / Serum-Interferonspiegel und (2'-5')-Oligo(A)-Synthetaseaktivität bei Pityriasis rosea, Basaliom, Melanom und Molluscum contagiosum.

In various skin diseases with a possible viral and/or autoimmune etiology, the peripheral lymphocytes were studied with regard to serum interferon levels and the interferon-induced activity of (2'-5')-oligoadenylate synthetase (OAS). This enzyme is a sensitive marker of interferon and can be detected even some days after the clearance of interferon from the blood. In patients with pityriasis rosea (n = 13), basal cell carcinoma (n = 12), malignant melanoma (n = 11), and molluscum contagiosum (n = 13), the serum interferon levels were not increased. In comparison to healthy persons, 5 patients with melanoma (Clark's levels I, I-II and II) showed a significantly elevated activity of OAS. In 6 other patients with melanoma (Clark's level III, III-IV and IV), the OAS activity was not increased. Although the elevated activity of OAS found in patients with melanoma of lower Clark's levels indicates a participation of the interferon system in the course of the disease, our results do not allow a clear statement regarding a viral and/or an autoimmune etiology of the skin disease.

[Optical hallucinations in the aged with diseases of the eye]. / Optische Halluzinationen bei älteren Menschen mit Erkrankungen des Auges.

Two cases of Charles Bonnet Syndrome (CBS) showing an unusual history are reported. In a 67-year-old man visual hallucinations developed 38 years after bilateral optic nerve damage due to methyl alcohol poisoning. A 78-year-old woman suffering from bilateral advanced cataract experienced visual hallucinations which ceased after improvement of vision resulting from cataract extraction. Sensory deprivation and--possibly--central neurophysiological disturbance are to be regarded as important pathogenetic factors. Signs of cerebral dysfunction which could be relevant to the pathogenesis of CBS were revealed by the EEG.

[Serum interferon level and (2'-5')-oligo(A) synthetase activity in malignant melanoma]. / Serum-Interferonspiegel und (2'-5')-Oligo(A)-Synthetaseaktivität bei malignem Melanom.

Both the serum levels of interferon and the activity of lymphocytic (2'-5')-oligoadenylate synthetase (OAS) of 37 patients suffering from malignant melanoma-15 with low (I,I-II,II) and 22 with higher (III,IV,V) Clark levels-were compared with those of a group of healthy controls in order to detect a possible involvement of the interferon system in the pathological process. Previous results obtained in studies on relatively small groups of patients had suggested that melanoma patients with low Clark levels (i.e. biologically early melanoma) show elevated activities of OAS, while those with higher levels show normal values. In our present investigation on a larger sample of patients, we did not find any differences between these two melanoma groups and healthy persons with regard to the OAS activity. Thus we were not able to confirm the provisional results set up by previous studies.