C. Krieg

The cellular anatomy of embryos of the nematode Caenorhabditis elegans: Analysis and reconstruction of serial section electron micrographs

Abstract As described from light microscopy, embryogenesis of the free-living soil nematode Caenorhabditis elegans follows a strictly determinate cleavage pattern, producing a newly hatched juvenile with about 550 cells arranged quite predictably. In this communication we present results on the electron microscopy of C. elegans embryos and introduce methods for fixing, embedding, and serially sectioning embryos encased in the egg shell. Fixation at elevated temperature either with osmium tetroxide alone or with glutaraldehyde followed by osmium tetroxide gives reproducible results with embryos in all developmental stages so far tested, from the fertilized egg to hatching. Eighteen wild-type eggs at various stages have been sectioned to date. We have achieved using newly developed procedures for analyzing electron micrographs of serial sections detailed reconstructions of the cellular anatomy of complete embryos of a metazoan organism. Three-dimensional serial section reconstructions were made with a computer system. We characterize and map the 24 cells of an early-stage embryo in this report. Additionally, we can specify the lineage history of all cells of this embyro by matching the reconstructed three-dimensional arrangement of this series to a living embryo at this stage, where cell lineage has been observed with Nomarski optics and analyzed using videotape ( U. Deppe, E. Schierenberg, T. Cole, C. Krieg, D. Schmitt, B. Yoder, and G. von Ehrenstein, 1978 , Proc. Nat. Acad. Sci. USA 75, 376–380). In addition, cytoplasmic and nuclear morphological features such as incomplete membranes between sister cells, rounding-off of the cytoplasm, and chromatin condensation patterns have been correlated with cell division. Mapping of such structures presents a new method by which supplementary lineage information can be obtained directly from an electron micrographic series.

Depressive neurosis. A long-term prospective and retrospective follow-up study of former inpatients.

ABSTRACT– The results of a 7‐year follow‐up study of 50 former psychiatric inpatients with a diagnosis of depressive neurosis (ICD 300.4) who met the RDC criteria for Major Depression are reported. The follow‐up assessment of the patients included the use of standardized social, psychological and psychopathological instruments. In addition, the course of illness as well as the utilization of medical services and periods of working disability was evaluated. The results indicate a rather unfavourable course and outcome in terms of symptoms for approximately 40% of the sample, including six patients who had committed suicide after index discharge. Almost 40% of the sample showed mild chronic symptoms with persistent impairments in social functioning especially in the area of social interaction, whereas only 20% of the sample were classified as satisfactorily improved or completely remitted.

Anxiety and depression: comorbidity, psychopathology, and social functioning.

A sample of 48 former nonpsychotic inpatients was studied with respect to the overlap of depression and anxiety. Particular emphasis was placed on social dysfunctions associated with anxiety disorder as both a pure and a mixed condition. Furthermore, another question examined was whether social dysfunctions represent a risk factor for the development of a severe depression. Almost 40% of patients with a DSM-III anxiety disorder (during the last 4 weeks before follow-up) simultaneously fulfilled the criteria of a depressive disorder, mainly those of a major depression. While the course of symptomatology for both the pure anxiety and the mixed group had been rather similar over a long period of time, social dysfunctions before index admission had been generally more pronounced in patients who later developed a severe secondary depression. Social dysfunctions of patients with both disorders are not exclusively explainable by a higher severity of symptoms or the presence of particular personality features.

Past and present strategies of research on the HPA‐axis in psychiatry.

Hypercortisolism in depression has been extensively studied during the last three decades. The main hypothesis regarding origin and clinical relevance of this phenomenon, however, has changed significantly. Up to the mid‐seventies hypercortisolism was conceived as consequence of stress modified by the degree of unconscious defense mechanisms in different forms of depressive or non‐depressive psychiatric disorders.

Cholinergic drugs as diagnostic and therapeutic tools in affective disorders

The hypothesis of a significant involvement of the cholinergic system in the pathogenesis of affective disorders still lacks strong experimental support. This is mainly because of missing specific peripheral markers of the central nervous activity of the cholinergic system and the lack of specific cholinergic agonists and antagonists without severe peripheral side effects. As the direct cholinergic agonist RS 86 seems to be more suitable because of its minor side effects, long half‐life and oral applicability, it was tested for its antimanic property and its effect on the hypothalamo‐pituitary adrenal system and the rapid eye movement (REM) sleep‐generating system. RS 86 exhibited antimanic and REM sleep‐inducing properties, but failed to stimulate the Cortisol system.

The Role of the Hypothalamus-Pituitary-Adrenocortical System in Depression

An increased activity of the hypothalamus-pituitary-adrenocortical system (HPAS) during episodes of depression has been reported by several investigators since the middle of the 1950s (Bryson and Martin 1954; Board et al. 1957; for review see Mason 1968; Rubin and Mandell 1966). As this phenomenon occurs only in a certain proportion of patients suffering from depression and disappears with clinical recovery (see, e.g., Kathol et al. 1984), it can be regarded as a state marker for some depressions, especially severe psychotic forms of endogenous depression (see Carroll et al. 1980; Rudorfer et al. 1982). Originally, HPAS activation in depression was hypothetically related to nonspecific stress induced by the disorder, e.g., via anxiety, inner tension, or other symptoms that seem to indicate a breakdown of ego defenses. This interpretation was, however, questioned on several grounds and finally rejected by most authorities in the field of psychoneuroendocrinology (e.g., Sachar 1975,1982; Carroll and Mendels 1976; Rubin and Kendler 1977; Rubin and Poland 1984). We will restrict our discussion of the problem to two arguments which we have empirically analyzed to some depth. They are both related to reports in the literature concerning the endogenous subtype of depression (melancholia). In this subtype the hyperactivity of the HPAS was found not only to be more pronounced than in other subtypes of the disorder but also to display melancholia-specific features which cannot be explained as stress phenomena.