Characterization of idiotopes on MOPC 315 IgA using monoclonal antiidiotypic antibodies

The isologous antiidiotypic response in BALB/c mice to immunization with the DNP-binding IgA myeloma protein, MOPC 315, alters the expression of the anti-DNP antibody repertoire and confers immunity against MOPC 315 myeloma tumors. In order to characterize the idiotopes on MOPC 315 IgA which elicit this response we have isolated four monoclonal antiidiotypic antibodies (AIA), D10 (IgG_2a), A2(IgG₁), G3 (IgG_2b) and F1 (IgG_2a), produced by splenocytes of BALB/c mice immunized with MOPC 315 IgA in three independent fusion experiments. These AIA react with MOPC 315 IgA. reassociated H³¹⁵ L³¹⁵ and F³¹⁵_V but not with free H³¹⁵, L³¹⁵, V³¹⁵_H or V³¹⁵₂. In addition the AIA do not react with the closely related DNP-binding IgA myeloma protein, MOPC 460, suggesting that they are directed against private idiotopes on MOPC 315 IgA. These idiotopes can be divided into two groups. Group I, defined by D10, A2 and G3 consists of two overlapping idiotopes, one of which is related to the hapten-binding site. The two idiotopes are formed by an interaction of amino acids in H³¹⁵ and L³¹⁵. Group II defined by F1 consists of one idiotope which is related to the hapten-binding site. This idiotope is comprised of an aminoacid sequence on H³¹⁵ which requires an interaction with either L³¹⁵ or L⁴⁶⁰ for expression. A2 and G3 react identically with the same idiotope but were derived from two independent fusion experiments. This indicates an identity of AIA clonotypes among individual mice and suggests that the isologous AIA response to MOPC 315 IgA is restricted.     

Mental retardation,macrocephaly, short stature and craniofacial dysmorphism in three sisters: A new entity among the mental retardation-macrocephaly syndromes?

In this report we describe a true macrocephaly-mental retardation syndrome in three sisters. In addition, they present a distinct craniofacial dysmorphism with coarse facial features. Further family investigation revealed a similar macrocephaly in the mother and her father, suggesting autosomal dominant transmission of this familial macrocephaly. Present knowledge of the nosology of the mental retardation-macrocephaly association is reviewed and discussed.     

Clinical applications of characteristic frequency measurements: preliminaryin vivo study

In vivo electrical impedance tomography images have been available for some years, and most of them show variation in impedance amplitude between two different states, for example between inspiration and expiration of the lungs. A refinement of the tomography technique has made it possible to show images of the complex impedance of the body. If several frequencies are used, more information on the investigated tissues can be collected, and new areas made available for investigation. It has been shown that tissues exhibit a characteristic frequency that can be derived from the maximum magnitude of the (negative) reactance. The characteristic frequency-related images can be calculated from several imaginary part curves obtained using the back-projection technique. The paper shows in vivo impedance spectra from different parts of the body, determines the characteristic frequency of the different in vivo measurements and suggests different applications of characteristic frequency imaging. Several data sets are collected to show the reproducibility of the measurements.     

Glutamate and aspartate immunoreactivity in cortico-cortical neurons of the sensorimotor cortex of rats

Summary Retrograde transport of tracers and immunocytochemistry have been used to determine if association and callosal neurons in the primary motor and somatosensory cortex of rats contain high levels of glutamate or aspartate and may, thus, use these amino acids as neurotransmitter. After tracer injections in these areas, about 65% of the retrogradely labeled neurons in layer V in the ipsilateral or contralateral hemisphere are immunopositive for glutamate. Lower percentages of double-labeled neurons are found in layers III, VI, and II. Similar results are obtained when sections are processed for aspartate immunoreactivity. About 90% of retrogradely labeled neurons are immunopositive in sections incubated with a mixture of both glutamateand aspartate antisera. These results suggest that a large fraction of cortico-cortical neurons are immunoreactive for either one amino acid but not for both. It is proposed that neurons with high levels of one amino acid use this as neurotransmitter; high levels of glutamate and aspartate are likely to be present in a fraction of neurons which may release both amino acids or a substance closely related to these.     

The juxtaglomerular apparatus in malignant hypertension of man

Summary Investigation of the behaviour of the renal Juxtaglomerular apparatus in 19 patients with malignant hypertension has shown that in kidneys fixed immediately after operation the Juxtaglomerular granulation index is twice as high as in autopsy kidneys. The formation of renin by the epitheloid cells begins with the appearance of osmiophilic substances in the region of the endoplasmic reticulum. The first stages of granule formation are small rhomboid particles in the Golgi cisternes, which aggregate to form bigger round or polymorphic granules in the Golgi area.In pathological conditions the substances synthesized may be set free and become active locally as a result of fibrinoid necrosis of the vascular wall. The rate of production is increased firstly by forcing rhe production of active agents in the preexistent epitheloid cells, secondly by transformation of the so-called bivalent cells and finally, by cell division.In accelerated hypertension the production of renin also takes place in nephrons whose glomeruli, tubules and macula densa, are damaged. There is a correlation between blood pressure elevation and the Juxtaglomerular granulation index.

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Zusammenfassung Untersuchungen über das Verhalten des juxtaglomerulären Zellkomplexes der Niere bei 19 Patienten mit maligner Hypertonie haben folgendes ergeben: In operativ gewonnenen und sofort fixierten Nieren ist der juxtaglomeruläre Granulationsindex doppelt so hoch wie in Nieren aus dem Sektionsgut. Die Reninbildung der epitheloiden Zellen beginnt mit dem Auftreten osmiophiler Substanzen im Bereich des endoplasmatischen Reticulums. Kleine rhomboide Gebilde in Golgizisternen sind Vorstufen von reifen Sekretgranula, die sich im Golgifeld zu größeren runden oder vielgestaltigen Sekrettropfen zusammenlagern.Unter pathologischen Bedingungen können infolge fibrinoider Gefäß- wandnekrosen Sekretsubstanzen lokal frei und lokal wirksam werden. Vermehrte Arbeitsleistung erfolgt zunächst durch Forcierung der Sekretproduktion in den präexistenten epitheloiden Zellen, sodann durch Transformierung sogenannter bivalenter Zellen und schließlich durch Zellneubildungen.Reninproduktion findet bei akzelerierter Hypertonie auch in solchen Nephronen statt, deren Glomerula und Tubuli samt Macula densa strukturell geschädigt sind. Es besteht eine Korrelation zwischen Höhe des Blutdruckes und Höhe des Granulationsindex.

     

The posterior pretectal nucleus: evidence for a direct projection to the inferior olive of the cat

In our horseradish peroxidase (HRP) study of the afferents to the medullary raphe nuclei in the cat, HRP uptake by damaged axons en route to the inferior olive (IO) was thought to be responsible for retrograde labelling of specific midbrain nuclei. To control for such indirect labelling, HRP was injected iontophoretically into the inferior olive. The location of retrogradely labelled neurons was related to the specific locus of HRP injection within the IO. Injection of HRP into the caudal dorsal accessory olive resulted in dense neuronal labelling in the ipsilateral caudal pole of the posterior pretectal nucleus (PPN). There was no labelling of the nucleus of Darkschevitch (Dk), interstitial nucleus of Cajal (ICA) or Edinger-Westphal nucleus (EW). In contrast, an injection focussed more rostrally, into the rostral, dorsal accessory, the medial accessory and the principal olive, produced dense labelling of Dk, ICA and EW; there was much less PPN labelling. It is concluded that labelling of Dk and PPN after HRP injections rostral to the IO, is due, at least in part, to uptake of HRP by damaged medial longitudinal fasciculus axons en route to the inferior olive. The direct PPN-inferior olivary projection provides a potential disynaptic retino-cerebellar connection, which may be involved in rapidly timed eye-body coordinate movements.     

Behavioral phenotyping of mice in pharmacological and toxicological research

The evaluation of behavioral effects is an important component for the in vivo screening of drugs or potentially toxic compounds in mice. Ideally, such screening should be composed of monitoring general health, sensory functions, and motor abilities, right before specific behavioral domains are tested. A rational strategy in the design and procedure of testing as well as an effective composition of different well-established and reproducible behavioral tests can minimize the risk of false positive and false negative results in drug screening. In the present review we describe such basic considerations in planning experiments, selecting strains of mice, and propose groups of behavioral tasks suitable for a reliable detection of differences in specific behavioral domains in mice. Screening of general health and neurophysiologic functions (reflexes, sensory abilities) and motor function (pole test, wire hang test, beam walking, rotarod, accelerod, and footprint) as well as specific hypothesis-guided testing in the behavioral domains of learning and memory (water maze, radial maze, conditioned fear, and avoidance tasks), emotionality (open field, hole board, elevated plus maze, and object exploration), nociception (tail flick, hot plate), psychiatric-like conditions (porsolt swim test, acoustic startle response, and prepulse inhibition), and aggression (isolation-induced aggression, spontaneous aggression, and territorial aggression) are described in further detail. This review is designed to describe a general approach, which increases reliability of behavioral screening. Furthermore, it provides an overview on a selection of specific procedures suitable for but not limited to behavioral screening in pharmacology and toxicology.     

Vitamin E content in the cortical and medullary layers of the mammalian kidney

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 115, N ^o 3, pp. 245–247, March, 1993     

The structuring of an allergy index based on IgE-mediated skin sensitivity to common environmental allergens

We computed skin-test sensitivity levels in 485 adults puncture-tested with eight standardized, high-quality inhalant allergens tested at single concentrations. In order to quantitate the "average" IgE-mediated skin sensitivity of each subject, we used both nonparametric and parametric statistical methods to generate two "allergy indices" (Allergy Index I and Allergy Index II) based on sensitivity end-point data from the subpopulations of individuals positive to six of the eight allergens. For the 192 skin test-positive subjects, Allergy Index I and Allergy Index II were significantly correlated with each other (rs = 0.98, p less than 0.001) and with the number of positive skin-test reactions (rs congruent to 0.9, p less than 0.001) as well as with log[total serum IgE] (r congruent to 0.4, p less than 0.01). In 102 ragweed-positive subjects, log[specific IgE to ragweed] was significantly correlated with ragweed-specific "ragweed indices I and II" (r congruent to 0.6, p less than 0.01). Furthermore, the average daily symptom scores reported by 14 ragweed-positive subjects during the ragweed pollination season were significantly correlated with ragweed indices I and II (p less than 0.05). We propose the use of Allergy Index II in epidemiologic and genetic studies of allergic phenotypes as well as in clinical decisions for diagnosis and immunotherapeutic intervention.