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Biomedical subjects

R Lüthy

Publications and source records attributed to R Lüthy.

At least 19 recordsLinked to original sources
PubMed1992

Disulfide bond assignment in human J chain and its covalent pairing with immunoglobulin M.

The assignment of disulfide bonds in human J chain and its covalent pairing with immunoglobulin M was determined under conditions which minimize disulfide bond interchange. We show that in J chain the three intradisulfide bridges are formed between Cys 12 and 100, Cys 71 and 91, and Cys 108 and 133. Previous reports [reviewed by Koshland, M. E. (1985) Annu. Rev. Immunol. 3, 425-453] have proposed that cysteines 12, 14, or 68 were linked to the penultimate cysteine 575 of two mu chain tails. In this work, we demonstrate that cysteines 14 and 68 are disulfide-bridged to mu chains. A revised, albeit putative, model of J chain folding is presented which takes into account the correct disulfide pairing and the predictive secondary structure assignment.

Amino Acid Sequence↗
PubMed1992

[Diagnosis and course of patients with HIV infections and exclusion of Pneumocystis carinii pneumonia].

30 patients infected with HIV (20 men, 10 women; mean age 34 [26-54] years), suspected of having Pneumocystis carinii (Pc) pneumonia, had undergone bronchoalveolar lavage which proved negative for Pc. They were then kept under observation for 5 months. No transbronchial biopsy was performed. 27 patients were in stage IV of the HIV infection, and 14 had been on pentamidine prophylaxis. The most frequent diagnosis with the bronchial lavage was bacterial infection (19 patients), next most frequent was mycobacterial infection (6, atypical in 5). A neoplasia (Kaposi sarcoma; non-Hodgkin lymphoma) was found in two, with pulmonary involvement. The diagnosis remained unclear in only three patients who were treated as for Pc pneumonia. The remaining 27 patients did not receive any treatment against Pc. Nonetheless, there were no cases of Pc pneumonia in the 5 months of observation so that bronchoalveolar lavage has a negative predictive value of 90% (27 of 30), high enough to make additional bronchial biopsy unnecessary.

Adult↗
PubMed1992

Assessment of protein models with three-dimensional profiles.

As methods for determining protein three-dimensional (3D) structure develop, a continuing problem is how to verify that the final protein model is correct. The revision of several protein models to correct errors has prompted the development of new criteria for judging the validity of X-ray and NMR structures, as well as the formation of energetic and empirical methods to evaluate the correctness of protein models. The challenge is to distinguish between a mistraced or wrongly folded model, and one that is basically correct, but not adequately refined. We show that an effective test of the accuracy of a 3D protein model is a comparison of the model to its own amino-acid sequence, using a 3D profile, computed from the atomic coordinates of the structure 3D profiles of correct protein structures match their own sequences with high scores. In contrast, 3D profiles for protein models known to be wrong score poorly. An incorrectly modelled segment in an otherwise correct structure can be identified by examining the profile score in a moving-window scan. The accuracy of a protein model can be assessed by its 3D profile, regardless of whether the model has been derived by X-ray, NMR or computational procedures.

Amino Acid Sequence↗
PubMed1992

Q fever endocarditis: diagnostic approaches and monitoring of therapeutic effects.

The scope of current diagnostic methods for Q fever endocarditis includes serology, direct demonstration of Coxiella burnetii in the resected heart valve tissue, and animal inoculation studies. Illustrated by a clinical case report, the different methods are presented and discussed. Serology represents the primary method, using the techniques of complement fixation, indirect immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). The latter two techniques allow the detection of immunoglobulins G, M, and A to the phase I and II antigens of C. burnetii. After cardiac surgery, we visualized C. burnetii on smears and specifically stained it on histologic sections of the resected heart valve by light and electron microscopic immunohistochemistry. In addition, seroconversion in animals after inoculation with valve specimens confirmed the presence of C. burnetii in the heart valve. The antibody titers determined by ELISA correlated well with the patient's clinical course during the treatment period. Therefore it is suggested that its usefulness for monitoring the efficacy of antimicrobial agents in patients with Q fever endocarditis should be further evaluated.

Endocarditis, Bacterial↗
PubMed1992

The effect of treatment with zidovudine with or without acyclovir on HIV p24 antigenaemia in patients with AIDS or AIDS-related complex.

OBJECTIVE: To evaluate changes in serum HIV p24-antigen levels in a subset of patients who participated in a European/Australian double-blind, placebo-controlled trial evaluating the efficacy of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) in patients with AIDS, AIDS-related complex (ARC) or Kaposi's sarcoma (KS). DESIGN: Double-blind, placebo-controlled randomized clinical trial of less than or equal to 6 months' therapy. SETTING: Samples were obtained from patients attending teaching hospital outpatient clinics in seven European countries and Australia. SUBJECTS: One hundred and ninety-seven HIV-infected patients (60 with AIDS and 137 with ARC or KS). MAIN OUTCOME MEASURES: Serum HIV p24-antigen levels measured using the Abbott HIV solid-phase enzyme immunoassay. RESULTS: Of 76 ARC/KS patients who were initially HIV p24-antigen-positive, one out of 25 randomized to placebo, eight out of 23 to zidovudine and 11 out of 28 to the zidovudine/acyclovir combination became antigen-negative. The proportion of patients who became antigen-negative was significantly higher in both the zidovudine group (P = 0.016) and the zidovudine/acyclovir group (P = 0.004), compared with the placebo group. There were no statistical differences between the zidovudine and the zidovudine/acyclovir groups. During the trial p24-antigen levels in the zidovudine-treated patients reached their minimum after 4-8 weeks of therapy, and tended to increase gradually thereafter. Disease progression occurred irrespective of whether p24-antigen levels declined during therapy. No association between p24-antigen responses to therapy and baseline disease stage, Karnofsky score or baseline CD4 cell count was detectable. CONCLUSION: Acyclovir does not potentiate the effect of zidovudine on p24-antigen levels. Change in antigen level in response to antiviral therapy needs further investigation before it is used as a surrogate marker for clinical efficacy of antiviral therapy.

AIDS-Related Complex↗
PubMed1992

Pulmonary and intestinal microsporidiosis in a patient with the acquired immunodeficiency syndrome.

The microsporidian protozoan organism Enterocytozoon bieneusi has been found in enterocytes of the small intestine in patients infected with human immunodeficiency virus, and it has been recognized as an important cause of chronic diarrhea in this patient group. We report the first case of a 41-yr-old man with acquired immunodeficiency syndrome in whom microsporidia were detected in bronchoalveolar lavage fluid, transbronchial lung biopsies, stool specimens, and ileal biopsies. He experienced chronic diarrhea, wasting syndrome, chronic cough, and dyspnea. His chest roentgenogram showed a small left posterobasal infiltrate and a small left pleural effusion. The histologic pattern of microsporidia in his bronchial and ileal tissue and the cellular inflammatory reaction with intraepithelial infiltration by lymphocytes were identical to findings described in duodenal and jejunal Enterocytozoon bieneusi microsporidiosis. An association between the presence of microsporidia in the lung and the pulmonary symptoms has yet to be determined. It is not known whether pulmonary microsporidiosis was acquired by the aerosol route, by aspiration, or by hematogenous dissemination from the intestine.

AIDS-Related Opportunistic Infections↗
PubMed1992

Three-dimensional profiles for analysing protein sequence-structure relationships.

In the method of 3D (three-dimensional) profiles, each residue position in a protein is characterized by its environment and is represented by a row of 20 numbers in a table, the profile. These numbers are the statistical preferences (called 3D-1D scores) of each of the 20 amino acids for this environment. A profile is computed from the coordinates of a protein model, and it gives a score S for any amino acid sequence folded as the model. To date 3D profiles have found three applications. The first is to identify other protein sequences which are folded in the same general pattern as the structure from which the profile was prepared. These are sequences which have high scores for the profile computed from the model. The second is to assess the validity of protein models, however determined. Correct models are found to give profiles that have high scores for their own amino acid sequences, and incorrect models are found to have lower scores. The example of the X-ray structure determination of diphtheria toxin is discussed. The third application is to assess which is the stable oligomeric state of a folded protein. Several examples suggest that the highest profile score for a sequence is achieved when the protein is aggregated into its most stable oligomeric state.

Amino Acid Sequence↗
PubMed1991

[Stenosis of the terminal portal vein branch in acute myeloid leukemia].

The endstage in a patient suffering from acute myeloid leukemia secondary to myelodysplastic syndrome was characterized by bleedings, anemia, pain in the upper abdomen and ascites. At autopsy the radicles of the portal veins were occluded by leukemic infiltrates and fibrosis. These lesions block the perfusion of the liver presinusoidally and, together with the anemia (hypoalbuminemia), result in ascites resistant to all therapy.

Ascites↗
PubMed1991

A method to identify protein sequences that fold into a known three-dimensional structure.

The inverse protein folding problem, the problem of finding which amino acid sequences fold into a known three-dimensional (3D) structure, can be effectively attacked by finding sequences that are most compatible with the environments of the residues in the 3D structure. The environments are described by: (i) the area of the residue buried in the protein and inaccessible to solvent; (ii) the fraction of side-chain area that is covered by polar atoms (O and N); and (iii) the local secondary structure. Examples of this 3D profile method are presented for four families of proteins: the globins, cyclic AMP (adenosine 3',5'-monophosphate) receptor-like proteins, the periplasmic binding proteins, and the actins. This method is able to detect the structural similarity of the actins and 70- kilodalton heat shock proteins, even though these protein families share no detectable sequence similarity.

Actins↗
PubMed1991

Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma.

A combination of oral zidovudine (250 mg twice daily) and subcutaneous interferon-alpha (10 x 10(6) units daily) was evaluated for clinical, antiretroviral, and immunological efficacy and for side effects in 17 patients with AIDS-related Kaposi's sarcoma. Fifteen patients were evaluable. During the study period of 12 weeks, tumor responses were complete in two patients and partial in two patients (27% major response rate). Minimal responses were seen in two patients (40% overall response rate). An anti-HIV effect (reduction of serum p24 antigen by 70% or more) was observed in seven of ten evaluable patients who were initially antigenemic. CD4 lymphocyte counts remained unchanged. In six patients who had either a tumor response or a marked decline of HIV antigenemia, the treatment was continued between 12 and 59 weeks beyond the study period. Two of four patients with tumor regression at 12 weeks had an additional tumor response in this period despite prior dose reduction of interferon due to toxicity. Late progression of KS was eventually observed in four of six patients on prolonged treatment. The responsiveness of Kaposi's sarcoma seen in this study in patients with low CD4 counts and prior constitutional symptoms (fever, weight loss) was unexpected and needs further confirmation by larger patient groups. Dose-limiting toxicities were bone marrow depression (severe anemia in four and neutropenia with anemia in two patients), subjective adverse experiences (fever, fatigue, myalgia; four patients) and both (two patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

[Anti-retroviral therapy of HIV-infection. With preliminary results of the Swiss postmarketing surveillance of zidovudine].

In the last few years, the treatment of HIV infection has advanced considerably due to the development of active antiretroviral compounds. Many substances with different mechanisms of action show strong activity against HIV in vitro and many of them are now under clinical investigation. But immense effort is needed to develop a clinically effective and tolerable drug for daily use from a substance active in vitro. Presently, zidovudine is the only drug that can be used for the treatment of HIV infection outside of clinical studies. The efficacy of zidovudine was demonstrated in patients with symptomatic HIV infection as well as in patients with advanced asymptomatic disease. The clinical signs of efficacy are significantly delayed progression of HIV infection and lower frequency of opportunistic infections, with decreased severity. It is evident that zidovudine does not cure the HIV infection. In Switzerland treatment with zidovudine is evaluated by post-marketing surveillance (PMS). All patients on zidovudine are seen periodically in the hospitals with a specialized division for HIV infection. Clinical and laboratory follow-ups are recorded. Until the beginning of October 1990, 1171 patients with symptomatic HIV infection have been treated with zidovudine in the setting of this PMS. 62% of all registered patients are currently receiving zidovudine. 20% died of AIDS. 15% of all patients received at least one blood transfusion. Hematotoxicity is the most frequent and serious side effect of zidovudine and can require definitive termination of therapy. The side effects are dose related and occur more severely in patients with advanced disease. The ideal dosage of zidovudine has not yet been defined. Recently published studies showed efficacy with doses as low as 500 mg/d. Consequently, patients in Switzerland receive 10 mg zidovudine/kg body weight as the maximum dose, divided into two or more single daily doses. Patients with asymptomatic HIV infection are regularly treated with 500 mg/d. Zidovudine-intolerant patients with symptomatic HIV infection can currently enter a controlled clinical trial of antiretroviral therapy with dideoxyinosine (ddI), which has a different spectrum of side effects but is only minimally toxic to bone marrow.

Didanosine↗
PubMed1991

[HIV infection and syphilis. Case description and literature review].

Recent case reports emphasize that HIV infection may influence the clinical picture, course and therapy of concurrent syphilis. The case of a 32-year-old patient with coinfection by T. pallidum and HIV is presented. Clinical presentation, diagnostic procedures and therapy are discussed in the light of the current literature. False negative serologic tests for syphilis in HIV-patients raise the question of the sensitivity of these tests in HIV infection. Efficacy of therapy for neurosyphilis and the value of CSF (cerebrospinal fluid) examination in early syphilis are of increased importance in HIV infection. Current guidelines for diagnosis and therapy of syphilis in HIV patients are outlined.

AIDS Serodiagnosis↗