Charge Detection Mass Spectrometry Enables Molecular Characterization of Nucleic Acid Nanoparticles.

Nucleic acid nanoparticles (NANPs) are increasingly used in preclinical investigations as delivery vectors. Tools that can characterize assembly and assess quality will accelerate their development and clinical translation. Standard techniques used to characterize NANPs, like gel electrophoresis, lack the resolution for precise characterization.

Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds.

Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses.

Functionalizing DNA origami to investigate and interact with biological systems.

DNA origami has emerged as a powerful method to generate DNA nanostructures with dynamic properties and nanoscale control. These nanostructures enable complex biophysical studies and the fabrication of next-generation therapeutic devices. For these applications, DNA origami typically needs to be functionalized with bioactive ligands and biomacromolecular cargos.

Evaluation of Nonmodified Wireframe DNA Origami for Acute Toxicity and Biodistribution in Mice.

Wireframe DNA origami can be used to fabricate virus-like particles for a range of biomedical applications, including the delivery of nucleic acid therapeutics. However, the acute toxicity and biodistribution of these wireframe nucleic acid nanoparticles (NANPs) have not been previously characterized in animal models. In the present study, we observed no indications of toxicity in BALB/c mice following a therapeutically relevant dosage of nonmodified DNA-based NANPs via intravenous administration, based on liver and kidney histology, liver and kidney biochemistry, and body weight.

Evaluation of non-modified wireframe DNA origami for acute toxicity and biodistribution in mice.

Wireframe DNA origami can be used to fabricate virus-like particles for a range of biomedical applications, including the delivery of nucleic acid therapeutics. However, the acute toxicity and biodistribution of these wireframe nucleic acid nanoparticles (NANPs) have not previously been characterized in animal models. In the present study, we observed no indications of toxicity in BALB/c mice following therapeutically relevant dosage of unmodified DNA-based NANPs via intravenous administration, based on liver and kidney histology, liver biochemistry, and body weight.

Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds.

Multivalent antigen display is a well-established principle to enhance humoral immunity. Protein-based virus-like particles (VLPs) are commonly used to spatially organize antigens. However, protein-based VLPs are limited in their ability to control valency on fixed scaffold geometries and are thymus-dependent antigens that elicit neutralizing B cell memory themselves, which can distract immune responses.

Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders.

Viruslike particles (VLPs) fabricated using wireframe DNA origami are emerging as promising vaccine and gene therapeutic delivery platforms due to their programmable nature that offers independent control over their size and shape, as well as their site-specific functionalization. As materials that biodegrade in the presence of endonucleases, specifically DNase I and II, their utility for the targeting of cells, tissues, and organs depends on their stability in vivo. Here, we explore minor groove binders (MGBs) as specific endonuclease inhibitors to control the degradation half-life of wireframe DNA origami.

Covalent Functionalization of DNA Origami Virus-like Particles.

DNA origami is a powerful nanomaterial for biomedical applications due in part to its capacity for programmable, site-specific functionalization. To realize these applications, scalable and efficient conjugation protocols are needed for diverse moieties ranging from small molecules to biomacromolecules. Currently, there are no facile and general methods for covalent modification and label-free quantification of reaction conversion.

Early onset vulvar Lichen Sclerosus in premenopausal women and oral contraceptives.

Objective: For vulvar Lichen sclerosus (LS) immunological factors, genetic predisposition, and decreased 5 alpha-reductase activity have been discussed as aetiological factors. During the last decade an increase of LS in young women has been suspected. Aim of this study was to evaluate data of premenopausal women with early onset LS to find potential risk factors focussing on the use of oral contraceptives.

[Prevalence of diabetes in acromegaly and Cushing syndrome].

In a retrospective study glucose metabolism was investigated in 206 patients with acromegaly and 131 patients with Cushing's disease. 40.5% of the patients with hypersomatotropism and 32.

Diagnosis of Cushing's syndrome: re-evaluation of midnight plasma cortisol vs urinary free cortisol and low-dose dexamethasone suppression test in a large patient group.

We studied plasma cortisol levels at 00:00 h and 08:00 h in 103 patients with Cushing's syndrome and 144 patients in whom this diagnosis had been excluded. These patients were hospitalized in our department from 1975 to 1996. Additionally, we measured these parameters in 20 healthy volunteers and in 5 patients with nonendocrine disease.

[The long-term therapy of hypothalamic-hypophyseal Cushing's syndrome with mitotane (o,p'-DDD)].

Background And Objective: Drug treatment of hypothalamic-pituitary Cushing's syndrome is indicated if standard surgical intervention is not possible or has failed. The question arises whether, after unsatisfactory treatment with various adrenostatic drugs, mitotane (o,p'-DDD), used against adrenal cortical cancer, is efficacious and free of significant side effects when used long-term.

Patients And Methods: The results of long-term administration of mitotane to six patients, including one pregnant woman, were analysed retrospectively.

[Pregnancy in hyperprolactinemic patients].

In a retrospective study we analysed the outcome of 27 pregnancies in 17 hyperprolactinaemic patients. Cranial CT or MRI scans showed a microadenoma in 9, a macroadenoma in 7 and no change in 1 case. In 5 patients macroadenomas were surgically removed but a residual hyperprolactinaemia remained.

[Cushing's syndrome in CRF-producing mediastinal carcinoid].

A 36-year-old patient developed marked pigmentation, marked myopathy and severe hypokalaemic alkalosis which at first pointed towards an ectopic ACTH syndrome. The dexamethasone test at a high dose indicated cortisol suppression. A mediastinal tumour was seen radiologically, but the sella was of normal size.

A 5 year interdisciplinary control of iodine deficiency in the GDR.

The interdisciplinary iodine prophylaxis in the GDR is a successful measure for control of ID. The iodization of nearly all the salt is planed perhaps with reduction of the iodine concentration. However, next further steps may be done in cooperation of the Interdisciplinary Iodine Commission with the "Arbeitskreis: Jodmangel" in the FRG.

Paradoxical response of plasma beta-endorphin to combined administration of TRH and GnRH in adrenal disorders.

The combined intravenous injection of TRH and GnRH elicited paradoxical responses of plasma beta-endorphin in active and successfully treated pituitary dependent Cushing's disease as well as in ectopic ACTH syndrome and in congenital adrenal hyperplasia. No response was observed in Cushing's syndrome due to adrenal tumours. It is concluded that an abnormal response to inappropriate releasing hormones cannot verify the existence of a pituitary corticotrophic microadenoma.

Interdisciplinary aspects of iodine prophylaxis in German Democratic Republic.

Endemic goiter still occurs in several European countries. Alimentary iodine deficiency could be proved as the main cause of endemic prevalence. Extensive epidemiologic surveys showed the great medical and economical impact of this matter for the GDR.

[The immunohistochemistry of pituitary adenomas].

A great deal of progress has been achieved in recent years in the field of immunohistochemistry of pituitary adenoma. Continued use of more new antisera and monoclonal antibodies against numerous hormones in the adenohypophysis have resulted in new approaches to classification of pituitary adenoma. However, new problems have been discovered, on the other hand, by large-scale studies in recent years.

Somatomedin-C in active and successfully treated acromegaly.

Sm-C concentrations in serum were found significantly different in either active acromegaly or following successful treatment with pituitary adenomectomy. Although after normalization of serum GH the Sm-C levels sometimes exceeded the normal range no overlap was found between both groups. Exceptionally two acromegalic patients showed elevated Sm-C levels in spite of normal GH values.

[Development and effectiveness of struma prevention in East Germany].

For the control of iodine deficiency disorders in man and animal since 1985/1986 measures have been introduced which were interdisciplinary attuned: 84% of the paketed salt are iodized (32 mg KIO3/kg) and iodized mixtures of mineral substances are used in the animal production of agricultural useful animals. The effectiveness of the iodine prevention becomes visible by an increase of the renal iodine excretion, regression of the frequency of connatal goitre and iodine deficiency disorders in the animal production. Increased manifestations of cases of hyperthyroidism as sequelae are of transient importance.

[Status of goiter prevention in East Germany from an interdisciplinary viewpoint].

The endemic goiter occurs still in many countries of Europe. Alimentary iodine deficiency could be proved as essential cause of the increased prevalence. Comprehensive epidemiological investigations refer to the medical importance of this appearance for the GDR.

[Current aspects of therapy of ovarian cancer. Surgical therapy of epithelial ovarian cancer at the Göttingen University Gynecologic Clinic. A retrospective analysis of 82 patients 1981-1984].

The most important step in the treatment of epithelial ovarian carcinoma is radical surgery which should be as radical as possible, since this can exercise a decisive influence on the effectiveness of subsequent chemotherapy or radiotherapy. During 1981-1984 98 patients with an ovarian carcinoma were operated upon. 82 of these patients had epithelial tumours that will be discussed in the article.